Methylphenidate to Improve Balance and Walking in MS

Multiple Sclerosis Clinical Trial

Official title:

Methylphenidate to Improve Balance and Walking in MS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01896700
• Other study ID #: 3055
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: July 8, 2013
• Last updated: March 8, 2018
• Start date: July 2013
• Est. completion date: April 2016

Study information

• Verified date: March 2018
• Source: Oregon Health and Science University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Methylphenidate is an amphetamine-like psychomotor stimulant drug currently approved for the treatment of attention-deficit hyperactivity disorder (ADHD), postural orthostasis tachycardia syndrome and narcolepsy. It is also often prescribed off label to people with MS to improve fatigue. It is proposed that methylphenidate may also improve imbalance and walking deficits in MS by improving concentration and central integration, one of the primary mechanisms thought to underlie imbalance and walking deficits in MS.

Description:

The proposed pilot study will examine the effects of methylphenidate on imbalance and walking in 24 subjects with MS and imbalance. The subjects will be randomly assigned to receive either an escalating does of methylphenidate, 20mg, 40mg or 60mg, divided into two doses each day, or matched placebo for 2 weeks at each dose. If a subject does not tolerate dose escalation they will be instructed to discontinue use of the drug. The maximum safely tolerated dose for each subject will be noted. Changes from baseline in subject's walking speed, balance, vestibular function, cognitive function, and fatigue will be assessed at each dose.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 65 Years

Eligibility

Inclusion Criteria:

• Age 20-65

• Able to walk at least 100m without an aide or with unilateral assistance

• Poor static balance, specifically prolonged APR latencies (= 1 standard deviation (SD) > mean for healthy people in this age range), OR

• Reduced balance-related activity (ABC scores = 85%)

• Walking difficulties, specifically T25FW > 6 seconds, OR reduced self perceived walking (MSWS-12 scores = 50/60)

Exclusion Criteria:

• Currently taking methylphenidate, modafinil, or armodafinil.(any within the last 2 weeks)

• Cause(s) of imbalance other than MS

• Systolic pressure consistently greater than 150 mm Hg or diastolic pressure consistently greater than 90 mm Hg

• Contraindications to methylphenidate (Anxiety, tension, agitation, thyrotoxicosis, tachyarrhythmias, severe angina pectoris or glaucoma, hypersensitivity to methylphenidate, motor tics or a family history or diagnosis of Tourette's syndrome, seizures, severe or poorly controlled hypertension, treatment with monoamine oxidase inhibitors currently or within the last 14 days, current use of guanethidine, pressors, coumarin anticoagulants, anticonvulsants, phenylbutazone, or tricyclic antidepressants, history of drug abuse or alcoholism)

• Pregnancy or breastfeeding

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Methylphenidate
Escalating dose of methylphenidate, 20mg, 40mg, 60mg/day, for 2 weeks each
• Placebo
Escalating matched dose of placebo

Locations

Country	Name	City	State
United States	Portland VA Medical Center	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
Oregon Health and Science University	Portland VA Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Timed Up and Go (TUG) Test Time at 6 Weeks	The primary outcome of this study will be the difference between mean change in TUG time between methylphenidate and placebo treated subjects at 6 weeks. Mean changes will be compared for active and placebo treated subjects using Bayesian analysis.	6 weeks
Secondary	Change From Baseline in Automatic Postural Response (APR) Latency at 6 Weeks	Mean changes in APR latency at 6 weeks will be compared for active and placebo treated subjects using Bayesian analysis.	6 weeks
Secondary	Change From Baseline in Timed 25 Foot Walk (T25FW) at 6 Weeks	Mean changes in Timed 25 Foot Walk (T25FW) at 6 weeks will be compared for active and placebo treated subjects using Bayesian analysis.	6 weeks
Secondary	Change From Baseline in Pittsburgh Sleep Quality Assessment Questionnaire Score at 6 Weeks	Mean changes in the score attained on the Pittsburgh Sleep Quality Assessment Questionnaire at 6 weeks will be compared for active and placebo treated subjects using Bayesian analysis. Scale ranges from 0-21 points, with higher numbers indicating poorer sleep quality.	6 weeks
Secondary	Change From Baseline in Modified Fatigue Index Scale Score at 6 Weeks	Mean changes in the score attached on the Modified Fatigue Index Scale at 6 weeks will be compared for active and placebo treated subjects using Bayesian analysis. Scale ranges from 0-84 points, with higher scores indicating greater fatigue.	6 weeks
Secondary	Change From Baseline in Vestibular-Ocular Reflex (VOR) Gain at 6 Weeks	The most common rotary chair testing is a battery of subtests, each at a specific rate (Hz) of chair rotation from side to side. The participant is secured in the chair in total darkness while the eyes are monitored by infrared cameras. We completed tests from 0.04 to 0.64 Hz to assess the vestibular system across a range of head movements. The chair and participant's head move together while the cameras track the velocity of the eyes; eye velocity reveals how the vestibular system responds to head velocity. VOR gain is the ratio of average chair (i.e. head) velocity to average eye velocity, and is represented on a unitless scale from 0 to 1. VOR gain close to 1 indicates that eye velocity is nearly equal and opposite to head velocity. While there are normative ranges for VOR gain, we are most interested in is change in mean gain (6-week tests minus baseline tests) for the active and placebo groups.	6 weeks
Secondary	Change From Baseline in Vestibular Ocular Reflex (VOR) Asymmetry (Percentage Asymmetric) at 6 Weeks	Mean changes in VOR asymmetry, which is a measure of the strength of the eye responses in one direction compared with the other as measured by rotary chair testing at 6 weeks, will be compared for active and placebo treated subjects using t-tests, or other appropriate statistical analyses. A range of frequencies was tested from 0.04 Hz to 0.64 Hz, as is standard for rotary chair testing. The range of frequencies (i.e. chair speeds) assesses the vestibular system across a range of head movements. This helps to identify abnormality, which may manifest at different frequencies of movement. The measurement outcomes for rotary chair testing are gain, phase and asymmetry of the eye movements.	6 weeks
Secondary	Change From Baseline in Vestibular Ocular Reflex (VOR) Phase (in Degrees) at 6 Weeks	Mean changes in VOR phase, which is a measure of the timing (in degrees) of the eye movements relative to the chair movement, as measured by rotary chair testing at 6 weeks, will be compared for active and placebo treated subjects using t-tests, or other appropriate statistical analyses. A range of frequencies was tested from 0.04 Hz to 0.64 Hz, as is standard for rotary chair testing. The range of frequencies (i.e. chair speeds) assesses the vestibular system across a range of head movements. This helps to identify abnormality, which may manifest at different frequencies of movement. The measurement outcomes for rotary chair testing are gain, phase and asymmetry of the eye movements.	6 weeks