Cannabis for Spasticity in Multiple Sclerosis

Multiple Sclerosis Clinical Trial

Official title:

Cannabis for Spasticity in Multiple Sclerosis: A Placebo-Controlled Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00682929
• Other study ID #: 251429
• Secondary ID: MS Society Award
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: April 14, 2004
• Est. completion date: August 17, 2011

Study information

• Verified date: April 2018
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to learn if the use of inhaled cannabis (marijuana) and oral cannabinoid (dronabinol, Marinol or THC, which is an active ingredient of marijuana) is safe and effective in reducing the symptoms of spasticity and tremor in patients with secondary-progressive or primary progressive multiple sclerosis.

Description:

The treatment of MS is far from satisfactory. For acute attacks, high dose corticosteroids seem to reduce the duration of attacks and to reduce the likelihood of future attacks. Immunomodulatory agents, available in this disease over the last decade, reduce the frequency of severe attacks by about one third. The remainder of the treatments are symptomatic, aimed at reducing the disability already present.

Recent research into the CB1 and CB2 cannabinoid receptor systems suggest that cannabis may have the potential for affecting both the pathogenic mechanisms and the symptoms of MS. In light of the autoimmune hypothesis of the etiology of MS, THC could directly alter immune function in a manner that might reduce (or increase) the primary pathology of the disease.

Comparisons: Three treatment arms will be compared:

1. inhaled cannabis and oral placebo

2. inhaled placebo and oral THC

3. inhaled placebo and oral placebo

The effects of these agents analyzed at 3 weeks and 7 weeks.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 41
• Est. completion date: August 17, 2011
• Est. primary completion date: August 17, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of clinically definite multiple sclerosis as defined by Poser criteria

• Moderate or severe spasticity

• Age 21 or older

• Must live close to the Sacramento, CA area

Exclusion Criteria:

• Preexisting pulmonary conditions, including poorly controlled asthma, chronic bronchitis, emphysema, bronchiectasis, and other significant pulmonary disorders

• Preexisting cardiac conditions, including ischemic heart disease, congestive heart failure, and other significant cardiac disorders

• Inability to abstain from tobacco or marijuana smoking, or use of alcohol or sedative or hypnotic medications during the duration of the study

• Pre-existing dementia, mania, depression or schizophrenia or other poorly controlled psychiatric illness

• Past history of abuse of recreational drugs, including marijuana and alcohol in the last 12 months

• History of or currently meets DSM-IV criteria for dependence on cannabis

• Use of cannabis, marijuana, or THC in the last four weeks

• Preexisting dementia, mania, depression, or schizophrenia or other poorly controlled psychiatric illness

• Exacerbation of MS within 30 days prior to screening visit

• Current use of cyclophosphamide, mitoxantrone, or cladribine

• Arthritis, bony and soft tissue disorders interfering with spasticity measures

• Inability to provide informed consent

• Recent cannabis use of more than twice per week one month prior to study entry

• For females of child bearing potential, inability to comply with adequate contraception

Related Conditions & MeSH terms

• Marijuana Abuse
• Multiple Sclerosis
• Muscle Spasticity
• Sclerosis

Intervention

Drug:
• Inhaled Cannabis
Participants will be instructed to smoke one cannabis cigarette, daily for 7 weeks.
• Oral THC
Participants will be instructed to take two 5 mg dronabinol tablets two hours prior to the inhaled medication, daily for 7 weeks.
• Oral Placebo
Participants will be instructed to take two placebo tablets two hours prior to the inhaled medication, daily for 7 weeks.
• Inhaled placebo
Participants will be instructed to smoke one placebo cigarette, daily for 7 weeks.

Locations

Country	Name	City	State
United States	University of California Davis Medical Center	Sacramento	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Davis	National Multiple Sclerosis Society

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Week 0 to Week 3 in the Rate of Torque Increase, Flexion	A modified servo-controlled torque motor system (Lido WorkSet II) was designed for this study to analyze the resistance to passive movement of the knee. It determines the amount of torque required to move the knee joint (without voluntary resistance) at high velocities (up to 200 degrees per second) and at slow velocities (as low as 10 degrees per second). The slow displacement torque is a measure of the passive resistance to movement (from the connective tissue and the non-contracting muscle) and the rapid displacement torques are the sum of the passive and active (involuntary) resistance. The active (involuntary) resistance is the result of the stretch reflex and correlates well with the clinical assessment of spasticity. The change was calculated by taking the value at Week 3 and subtracting the value at Week 0. A negative result indicates a decrease in the torque measured and correlates to a decrease in spasticity and a better outcome.	Week 0, Week 3
Primary	Change From Week 0 to Week 3 in the Rate of Torque Increase, Extension	A modified servo-controlled torque motor system (Lido WorkSet II) was designed for this study to analyze the resistance to passive movement of the knee. It determines the amount of torque required to move the knee joint (without voluntary resistance) at high velocities (up to 200 degrees per second) and at slow velocities (as low as 10 degrees per second). The slow displacement torque is a measure of the passive resistance to movement (from the connective tissue and the non-contracting muscle) and the rapid displacement torques are the sum of the passive and active (involuntary) resistance. The active (involuntary) resistance is the result of the stretch reflex and correlates well with the clinical assessment of spasticity. The change was calculated by taking the value at Week 3 and subtracting the value at Week 0. A negative result indicates a decrease in the torque measured and correlates to a decrease in spasticity and a better outcome.	Week 0, Week 3
Primary	Change From Week 0 to Week 7 in the Rate of Torque Increase, Flexion	A modified servo-controlled torque motor system (Lido WorkSet II) was designed for this study to analyze the resistance to passive movement of the knee. It determines the amount of torque required to move the knee joint (without voluntary resistance) at high velocities (up to 200 degrees per second) and at slow velocities (as low as 10 degrees per second). The slow displacement torque is a measure of the passive resistance to movement (from the connective tissue and the non-contracting muscle) and the rapid displacement torques are the sum of the passive and active (involuntary) resistance. The active (involuntary) resistance is the result of the stretch reflex and correlates well with the clinical assessment of spasticity. The change was calculated by taking the value at Week 7 and subtracting the value at Week 0. A negative result indicates a decrease in the torque measured and correlates to a decrease in spasticity and a better outcome.	Week 0, Week 7
Primary	LIDO Machine Score - Rate of Torque Increase, Extension	A modified servo-controlled torque motor system (Lido WorkSet II) was designed for this study to analyze the resistance to passive movement of the knee. It determines the amount of torque required to move the knee joint (without voluntary resistance) at high velocities (up to 200 degrees per second) and at slow velocities (as low as 10 degrees per second). The slow displacement torque is a measure of the passive resistance to movement (from the connective tissue and the non-contracting muscle) and the rapid displacement torques are the sum of the passive and active (involuntary) resistance. The active (involuntary) resistance is the result of the stretch reflex and correlates well with the clinical assessment of spasticity. The change was calculated by taking the value at Week 7 and subtracting the value at Week 0. A negative result indicates a decrease in the torque measured and correlates to a decrease in spasticity and a better outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in Modified Ashworth Score (MAS)	The Modified Ashworth scale measures resistance during passive soft-tissue stretching. Spasticity is graded on a scale of 0 (no increase in muscle tone) to 4 (affected part rigid in flexion or extension). The highest score (flexion or extension), for the lower extremities only, was used for each subject. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates a decrease in spasticity and correlates to a better outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in Modified Ashworth Score	The Modified Ashworth scale measures resistance during passive soft-tissue stretching. Spasticity is graded on a scale of 0 (no increase in muscle tone) to 4 (affected part rigid in flexion or extension). The highest score (flexion or extension), for the lower extremities only, was used for each subject. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates a decrease in spasticity and correlates to a better outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in Ambulation Index (AI) Score	The AI is a 9-point rating scale used to assess mobility by evaluating the time and degree of assistance required to walk 25 feet. Scores range from 0 (asymptomatic, fully active) to 9 (restricted to wheelchair, unable to transfer self independently). Lower scores represent a better outcome for MS patients. For this study, the AI score was based on the results of the 25 Foot Walk test, also performed at the study visit. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result for this outcome indicates an improvement in ambulation and correlates to a better outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in Ambulation Index (AI) Score	The AI is a 9-point rating scale used to assess mobility by evaluating the time and degree of assistance required to walk 25 feet. Scores range from 0 (asymptomatic, fully active) to 9 (restricted to wheelchair, unable to transfer self independently). Lower scores represent a better outcome for MS patients. For this study, the AI score was based on the results of the 25 Foot Walk test, also performed at the study visit. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result for this outcome indicates an improvement in ambulation and correlates to a better outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in 25 Foot Walk Time	The Timed 25 Foot Walk is a quantitative measure of lower extremity function. The patient is instructed to walk on a marked 25-foot course, as quickly and as safely as possible. The patient is allowed to use his/her typical walking aid, if applicable. The task is completed twice and the average time of the two trials was used for this outcome measure. The change was calculated by taking the Week 3 time and subtracting the Week 0 time. A negative result indicates an improvement in walking ability and correlates to a better outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in 25 Foot Walk Time	The Timed 25 Foot Walk is a quantitative measure of lower extremity function. The patient is instructed to walk on a marked 25-foot course, as quickly and as safely as possible. The patient is allowed to use his/her typical walking aid, if applicable. The task is completed twice and the average time of the two trials was used for this outcome measure. The change was calculated by taking the Week 7 time and subtracting the Week 0 time. A negative result indicates an improvement in walking ability and correlates to a better outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in 9 Hole Peg Test (Dominant Hand) Time	The 9 hold peg test is a quantitative measure of upper extremity (arm and hand function). Patients are instructed to fill an 9 hole peg board with 1 peg at a time and then immediately remove the pegs, 1 at a time. The dominant hand is tested twice and the average time was used for this outcome measure. The change was calculated by taking the Week 3 time and subtracting the Week 0 time.; A negative result indicates an improvement in arm and hand function and correlates with a better outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in 9 Hole Peg Test (Dominant Hand) Time	The 9 hold peg test is a quantitative measure of upper extremity (arm and hand function). Patients are instructed to fill an 9 hole peg board with 1 peg at a time and then immediately remove the pegs, 1 at a time. The dominant hand is tested twice and the average time was used for this outcome measure. The change was calculated by taking the Week 7 time and subtracting the Week 0 time.; A negative result indicates an improvement in arm and hand function and correlates with a better outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in 9 Hole Peg Test (Non- Dominant Hand) Time	The 9 hold peg test is a quantitative measure of upper extremity (arm and hand function). Patients are instructed to fill an 9 hole peg board with 1 peg at a time and then immediately remove the pegs, 1 at a time. The non-dominant hand is tested twice and the average time was used for this outcome measure. The change was calculated by taking the Week 3 time and subtracting the Week 0 time.; A negative result indicates an improvement in arm and hand function and correlates with a better outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in 9 Hole Peg Test (Non- Dominant Hand) Time	The 9 hold peg test is a quantitative measure of upper extremity (arm and hand function). Patients are instructed to fill an 9 hole peg board with 1 peg at a time and then immediately remove the pegs, 1 at a time. The dominant hand is tested twice and the average time was used for this outcome measure. The change was calculated by taking the Week 7 time and subtracting the Week 0 time.; A negative result indicates an improvement in arm and hand function and correlates with a better outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in Paced Auditory Serial Addition Test (PASAT) Score	The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability; The test is presented via recording on a CD to control the rate of stimulus presentation. Single digits are presented every 3 seconds and the patient must add each new digit to the one immediately prior to it. The test score is the number of correct sums given (out of a possible 60) in each trial. There are 2 test forms, A and B. The forms were alternated and at least 1 practice test (10 sums) was performed prior to each trial. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in performance and correlates with a better outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in Paced Auditory Serial Addition Test (PASAT) Score	The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability; The test is presented via recording on a CD to control the rate of stimulus presentation. Single digits are presented every 3 seconds and the patient must add each new digit to the one immediately prior to it. The test score is the number of correct sums given (out of a possible 60) in each trial. There are 2 test forms, A and B. The forms were alternated and at least 1 practice test (10 sums) was performed prior to each trial. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in performance and correlates with a better outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in Functional System Score - Vision	The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Vision score is determined by a 7-point scale, with 0 being the lowest (normal) and 6 being the highest (grade 5 plus maximal visual acuity of better eye of 20/60 (0.3) or less).; Higher values indicate more impaired vision. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in vision and correlates to a better outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in Functional System Score - Vision	The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Vision score is determined by a 7-point scale, with 0 being the lowest (normal) and 6 being the highest (grade 5 plus maximal visual acuity of better eye of 20/60 (0.3) or less).; Higher values indicate more impaired vision. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in vision and correlates to a better outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in Functional System Score - Brainstem	The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Brainstem score is determined by a 6-point scale, with 0 being the lowest (normal) and 5 being the highest (inability to swallow or speak). Higher values indicate more impaired function. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in Functional System Score - Brainstem	The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Brainstem score is determined by a 6-point scale, with 0 being the lowest (normal) and 5 being the highest (inability to swallow or speak). Higher values indicate more impaired function. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in Functional System Score - Pyramidal	The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Pyramidal score is determined by a 7-point scale, with 0 being the lowest (normal) and 6 being the highest (tetraplegia (grade 0 or 1 in all muscle groups of upper and lower limbs). Higher values indicate more impaired function. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in Functional System Score - Pyramidal	The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Pyramidal score is determined by a 7-point scale, with 0 being the lowest (normal) and 6 being the highest (tetraplegia (grade 0 or 1 in all muscle groups of upper and lower limbs). Higher values indicate more impaired function. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in Functional System Score - Cerebellar	The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Cerebellar score is determined by a 6-point scale, with 0 being the lowest (normal) and 5 being the highest (unable to perform coordinated movements due to ataxia). Higher values indicate more impaired function. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in Functional System Score - Cerebellar	The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Cerebellar score is determined by a 6-point scale, with 0 being the lowest (normal) and 5 being the highest (unable to perform coordinated movements due to ataxia). Higher values indicate more impaired function. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in Functional System Score - Sensory	The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Sensory score is determined by a 7-point scale, with 0 being the lowest (normal) and 6 being the highest (sensation essentially lost below the head). Higher values indicate more impaired function. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in Functional System Score - Sensory	The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Sensory score is determined by a 7-point scale, with 0 being the lowest (normal) and 6 being the highest (sensation essentially lost below the head). Higher values indicate more impaired function. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in Functional System Score - Bowel and Bladder	The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Bowel and Bladder score is determined by a 7-point scale, with 0 being the lowest (normal) and 6 being the highest (loss of bowel and bladder function). Higher values indicate more impaired function. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in Functional System Score - Bowel and Bladder	The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Bowel and Bladder score is determined by a 7-point scale, with 0 being the lowest (normal) and 6 being the highest (loss of bowel and bladder function). Higher values indicate more impaired function. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in Functional System Score - Cerebral	The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Cerebral score is determined by a 6-point scale, with 0 being the lowest (normal) and 5 being the highest (dementia). Higher values indicate more impaired function. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome. Fatigue did not contribute to this FS score or the EDSS total score.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in Functional System Score - Cerebral	The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The FS Cerebral score is determined by a 6-point scale, with 0 being the lowest (normal) and 5 being the highest (dementia). Higher values indicate more impaired function. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome. Fatigue did not contribute to this FS score or the EDSS total score.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in Expanded Disability Status Score (EDSS)	The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The total EDSS score ranges from 0 to 10, in 0.5 unit increments. A score of 0 is the lowest (normal neurological exam) and 10 is the highest (death due to MS). Higher values indicate more impaired function. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in Expanded Disability Status Score (EDSS)	The EDSS is a method of quantifying disability in MS patients and monitoring changes in the level of disability over time. The EDSS quantifies disability in 7 functional systems (FS): visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral, and includes a measure of ambulation. Neurostatus version 10/2002 was used for this study. The total EDSS score ranges from 0 to 10, in 0.5 unit increments. A score of 0 is the lowest (normal neurological exam) and 10 is the highest (death due to MS). Higher values indicate more impaired function. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in function and correlates to a better outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in MS Quality of Life Inventory (MSQLI) - SF-36 Physical Component Score	The SF-36 is a 36-item scale developed as a generic health status measure. It is a part of the MS Quality of Life Inventory. It can be reported as 2 summary scales - the Physical and Mental components. The scale is measured from 0 -100. The scale is set up so that a higher score indicates better health. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A positive result indicates an improvement in health status and correlates to a better outcome. A negative result indicates a decline in health and correlates to a worse outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in MS Quality of Life Inventory (MSQLI) - SF-36 Physical Component Score	The SF-36 is a 36-item scale developed as a generic health status measure. It is a part of the MS Quality of Life Inventory. It can be reported as 2 summary scales - the Physical and Mental components. The scale is measured from 0 -100. The scale is set up so that a higher score indicates better health. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A positive result indicates an improvement in health status and correlates to a better outcome. A negative result indicates a decline in health and correlates to a worse outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in MS Quality of Life Inventory (MSQLI) - SF-36 Mental Component Score	The SF-36 is a 36-item scale developed as a generic health status measure. It is a part of the MS Quality of Life Inventory. It can be reported as 2 summary scales - the Physical and Mental components. The scale is measured from 0 -100. The scale is set up so that a higher score indicates better health. The change was calculated by taking the Week 3 score and subtracting the Week 0. A positive result indicates an improvement in mental health status and correlates to a better outcome. A negative result indicates a decline in mental health and correlates to a worse outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in MS Quality of Life Inventory (MSQLI) - SF-36 Mental Component	The SF-36 is a 36-item scale developed as a generic health status measure. It is a part of the MS Quality of Life Inventory. It can be reported as 2 summary scales - the Physical and Mental components. The scale is measured from 0 -100. The scale is set up so that a higher score indicates better health. The change was calculated by taking the Week 3 score and subtracting the Week 0. A positive result indicates an improvement in mental health status and correlates to a better outcome. A negative result indicates a decline in mental health and correlates to a worse outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week3 in MS Quality of Life Inventory (MSQLI) - Modified Fatigue Index Score	The Modified Fatigue Index is a 21-item scale developed to assess the perceived impact of fatigue on daily activities. It is a part of the MS Quality of Life Inventory. The scale is measured from 0-84. The scale is set up so that a higher score indicates a greater impact of fatigue on a patient's daily activities. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates a decrease in the impact of fatigue on daily activities and correlates to a better outcome. A positive result indicates an increase in the impact of fatigue on daily activities and correlates to a worse outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in MS Quality of Life Inventory (MSQLI) - Modified Fatigue Index Score	The Modified Fatigue Index is a 21-item scale developed to assess the perceived impact of fatigue on daily activities. It is a part of the MS Quality of Life Inventory. The scale is measured from 0 - 84. The scale is set up so that a higher score indicates a greater impact of fatigue on a patient's daily activities. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates a decrease in the impact of fatigue on daily activities and correlates to a better outcome. A positive result indicates an increase in the impact of fatigue on daily activities and correlates to a worse outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in MS Quality of Life Inventory (MSQLI) - Pain Effects Scale Score	The Pain Effects Scale is a 6-item scale developed to assess the effects of pain on behavior and mood. It is a part of the MS Quality of Life Inventory. The scale is measured from 6-30. The scale is set up so that a higher score indicates a greater impact of pain on a patient's mood and behavior. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates a decrease in the impact of pain on mood and behavior and correlates to a better outcome. A positive result indicates an increase in the impact of pain on mood and behavior and correlates to a worse outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in MS Quality of Life Inventory (MSQLI) - Pain Effects Scale Score	The Pain Effects Scale is a 6-item scale developed to assess the effects of pain on behavior and mood. It is a part of the MS Quality of Life Inventory. The scale is measured from 6-30. The scale is set up so that a higher score indicates a greater impact of pain on a patient's mood and behavior. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates a decrease in the impact of pain on mood and behavior and correlates to a better outcome. A positive result indicates an increase in the impact of pain on mood and behavior and correlates to a worse outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in MS Quality of Life Inventory (MSQLI) - Sexual Satisfaction Scale Score	The Sexual Satisfaction Scale is a 4-item scale developed to assess the impact of multiple sclerosis on sexual function and satisfaction. It is a part of the MS Quality of Life Inventory. The scale is measured from 4-24. The scale is set up so that a higher score indicates greater problems with sexual satisfaction. Subjects that answered "No" to the question, "Do you have a relationship with one primary partner", did not complete the scale. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in sexual satisfaction and correlates to a better outcome. A positive result indicates a decrease in sexual satisfaction and correlates to a worse outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in MS Quality of Life Inventory (MSQLI) - Sexual Satisfaction Scale Score	The Sexual Satisfaction Scale is a 4-item scale developed to assess the impact of multiple sclerosis on sexual function and satisfaction. It is a part of the MS Quality of Life Inventory. The scale is measured from 4-24. The scale is set up so that a higher score indicates greater problems with sexual satisfaction. Subjects that answered "No" to the question, "Do you have a relationship with one primary partner", did not complete the scale. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in sexual satisfaction and correlates to a better outcome. A positive result indicates a decrease in sexual satisfaction and correlates to a worse outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in MS Quality of Life Inventory (MSQLI) - Bladder Control Scale Score	The Bladder Control Scale is a 4-item scale developed to assess the impact of multiple sclerosis on bladder function. It is a part of the MS Quality of Life Inventory. The scale is measured from 0-22. The scale is set up so that a higher score indicates greater bladder control problems. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in bladder control and correlates to a better outcome. A positive result indicates a decrease in bladder control and correlates to a worse outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in MS Quality of Life Inventory (MSQLI) - Bladder Control Scale Score	The Bladder Control Scale is a 4-item scale developed to assess the impact of multiple sclerosis on bladder function. It is a part of the MS Quality of Life Inventory. The scale is measured from 0-22. The scale is set up so that a higher score indicates greater bladder control problems. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in bladder control and correlates to a better outcome. A positive result indicates a decrease in bladder control and correlates to a worse outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in MS Quality of Life Inventory (MSQLI) - Bowel Control Scale Score	The Bowel Control Scale is a 5-item scale developed to assess the impact of multiple sclerosis on bowel function. It is a part of the MS Quality of Life Inventory. The scale is measured from 0-26. The scale is set up so that a higher score indicates greater bowel control problems. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates an improvement in bowel control and correlates to a better outcome. A positive result indicates a decrease in bowel control and correlates to a worse outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in MS Quality of Life Inventory (MSQLI) - Bowel Control Scale Score	The Bowel Control Scale is a 5-item scale developed to assess the impact of multiple sclerosis on bowel function. It is a part of the MS Quality of Life Inventory. The scale is measured from 0-26. The scale is set up so that a higher score indicates greater bowel control problems. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates an improvement in bowel control and correlates to a better outcome. A positive result indicates a decrease in bowel control and correlates to a worse outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in MS Quality of Life Inventory (MSQLI) - Impact of Visual Impairment Scale Score	The Impact of Visual Impairment Scale is a 5-item scale developed to assess the extent to which activities dependent on vision are affected by MS-related visual problems. It is a part of the MS Quality of Life Inventory. The scale is measured from 0-15. The scale is set up so that a higher score indicates greater impact of visual problems on daily activities. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates a decrease in the impact of visual problems on daily activities and correlates to a better outcome. A positive result indicates an increase in the impact of visual problems on daily activities and correlates to a worse outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in MS Quality of Life Inventory (MSQLI) - Impact of Visual Impairment Scale Score	The Impact of Visual Impairment Scale is a 5-item scale developed to assess the extent to which activities dependent on vision are affected by MS-related visual problems. It is a part of the MS Quality of Life Inventory. The scale is measured from 0-15. The scale is set up so that a higher score indicates greater impact of visual problems on daily activities. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates a decrease in the impact of visual problems on daily activities and correlates to a better outcome. A positive result indicates an increase in the impact of visual problems on daily activities and correlates to a worse outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in MS Quality of Life Inventory (MSQLI) - Perceived Deficits Scale Score	The Perceived Deficits Scale is a 20-item scale developed to assess the patient's perceived cognitive deficits. It is composed of four 5-item subscales: Attention/Concentration, Retrospective Memory, Prospective Memory, and Planning/Organization. It is a part of the MS Quality of Life Inventory. The total score is measured from 0-80. The scale is set up so that a higher score indicates greater perceived cognitive impairment. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A negative result indicates a decrease in the perception of cognitive impairment. A positive result indicates an increase in the perception of cognitive impairment. Since patient perceptions of cognitive impairment may not correlate with objective measures of cognitive impairment, the results should be interpreted with caution.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in MS Quality of Life Inventory (MSQLI) - Perceived Deficits Scale Score	The Perceived Deficits Scale is a 20-item scale developed to assess the patient's perceived cognitive deficits. It is composed of four 5-item subscales: Attention/Concentration, Retrospective Memory, Prospective Memory, and Planning/Organization. It is a part of the MS Quality of Life Inventory. The total score is measured from 0-80. The scale is set up so that a higher score indicates greater perceived cognitive impairment. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A negative result indicates a decrease in the perception of cognitive impairment. A positive result indicates an increase in the perception of cognitive impairment. Since patient perceptions of cognitive impairment may not correlate with objective measures of cognitive impairment, the results should be interpreted with caution.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in MS Quality of Life Inventory (MSQLI) - Mental Health Inventory Scale Score	The Mental Health Inventory (MHI) is an 18-item scale developed as a measure of overall emotional functioning. It is a part of the MS Quality of Life Inventory. The total score is measured from 0-100. The scale is set up so that a higher score indicates better mental health. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A positive result indicates an improvement in mental health and correlates to a better outcome. A negative result indicates decrease in mental health and correlates to a worse outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in MS Quality of Life Inventory (MSQLI) - Mental Health Inventory Scale Score	The Mental Health Inventory (MHI) is an 18-item scale developed as a measure of overall emotional functioning. It is a part of the MS Quality of Life Inventory. The total score is measured from 0-100. The scale is set up so that a higher score indicates better mental health. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A positive result indicates an improvement in mental health and correlates to a better outcome. A negative result indicates decrease in mental health and correlates to a worse outcome.	Week 0, Week 7
Secondary	Change From Week 0 to Week 3 in MS Quality of Life Inventory (MSQLI) - Modified Social Support Scale Score	The Modified Social Support Scale is an 18-item scale developed as a measure of perceived social support. It is a part of the MS Quality of Life Inventory. The total score is measured from 0-100. The scale is set up so that a higher score indicates greater perceived support. The change was calculated by taking the Week 3 score and subtracting the Week 0 score. A positive result indicates an improvement in perceived support and correlates to a better outcome. A negative result indicates a decrease in perceived support and correlates to a worse outcome.	Week 0, Week 3
Secondary	Change From Week 0 to Week 7 in MS Quality of Life Inventory (MSQLI) - Modified Social Support Scale Score	The Modified Social Support Scale is an 18-item scale developed as a measure of perceived social support. It is a part of the MS Quality of Life Inventory. The total score is measured from 0-100. The scale is set up so that a higher score indicates greater perceived support. The change was calculated by taking the Week 7 score and subtracting the Week 0 score. A positive result indicates an improvement in perceived support and correlates to a better outcome. A negative result indicates a decrease in perceived support and correlates to a worse outcome.	Week 0, Week 7