Clinical Trial Ceftriaxone in Subjects With ALS

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

Clinical Trial Ceftriaxone in Subjects With Amyotrophic Lateral Sclerosis (ALS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00349622
• Other study ID #: U01NS049640-02
• Secondary ID: NINDSU01NS049640
• Status: Completed
• Phase: Phase 3
• First received: July 5, 2006
• Last updated: April 1, 2014
• Start date: July 2006
• Est. completion date: November 2012

Study information

• Verified date: April 2014
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate the safety and efficacy of ceftriaxone treatment in amyotrophic lateral sclerosis (ALS).

Description:

It is known that nerve cells called motor neurons die in the brains and spinal cords of people with amyotrophic lateral sclerosis (ALS). However, the cause of this cell death is unknown. Researchers think that increased levels of a chemical called "glutamate" may be related to the cell death. For this reason researchers want to study drugs that decrease glutamate levels near nerves. Ceftriaxone—a semi-synthetic, third generation cephalosporin antibiotic—may increase the level of a protein that decreases glutamate levels near nerves. Studies of ceftriaxone in the laboratory suggest that it may protect motor neurons from injury.

Ceftriaxone is approved by the U.S. Food and Drug Administration (FDA) for treating bacterial infections but not for treating ALS. Also, ceftriaxone has not been given to people over a long period of time, such as months or years. The goals of this study are to evaluate the safety and effectiveness of ceftriaxone as a treatment for ALS, and to determine the safety and effectiveness of long-term use of the drug in people with ALS.

A total of 600 eligible people with ALS will be enrolled in this multi-center research study. Participants will be randomly assigned to receive treatment with ceftriaxone (2/3 of participants) or placebo (1/3 of participants) for at least 12 months.

The study consists of three stages. The first stage, which has completed enrollment, will look at whether ceftriaxone enters the cerebrospinal fluid (the fluid that surrounds the spinal cord, also called CSF) in amounts that are high enough to be of possible benefit. The second stage, which has also completed enrollment, will look at the safety and side effects of the study drug when taken daily for at least 20 weeks. The study is currently enrolling subjects for the third stage, which began in Spring 2009, and will determine whether the study drug prolongs survival and slows decline in function due to ALS.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 513
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants will be people with ALS, at least 18 years of age.

• Participants must be medically able to undergo the study procedures and have a caregiver or other individual who will be available to help with daily study medication administration.

• Participants should live within a reasonable distance of the study site, due to frequent study visits.

Exclusion Criteria:

• Participants cannot be taking any other experimental medications for ALS, or have a history of sensitivity to cephalosporin antibiotics (such as Ancef, Keflex, Ceclor, Ceftin, Lorabid, Suprax, or Fortaz).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• ALS
• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• ceftriaxone
Participants will be randomly assigned to receive treatment with ceftriaxone or placebo for at least 12 months. Two thirds of participants will receive ceftriaxone and one third will receive placebo. This is a blinded study, so neither participants nor study staff will know which treatment a participant is receiving. Ceftriaxone is approved by the U.S. Food and Drug Administration (FDA) for treating bacterial infections but not for treating ALS. Also, ceftriaxone has not been given to people over a long period of time, such as months or years.

Other:
• placebo
an inactive substance

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	Univeristy of Alberta ALS Clinic	Edmonton	Alberta
Canada	Dalhousie University	Halifax	Nova Scotia
Canada	London Health Sciences Center, University Campus	London	Ontario
Canada	CHUM (Centre Hospitalier de l'Université de Montréal), Notre-Dame Hospital	Montreal	Quebec
Canada	Montreal Neurological Institute (McGill University)	Montreal	Quebec
Canada	Laval University	Quebec City	Quebec
Canada	University of Toronto	Toronto	Ontario
United States	Albany Medical Center	Albany	New York
United States	ALS Center at Emory University	Atlanta	Georgia
United States	Medical College of Georgia	Augusta	Georgia
United States	University of Colorado Health Sciences Center	Aurora	Colorado
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Lahey Clinic	Burlington	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Northwestern University Medical School	Chicago	Illinois
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Texas Neurology	Dallas	Texas
United States	University of California, Davis	Davis	California
United States	Henry Ford Health System	Detroit	Michigan
United States	University of California, San Francisco- Fresno	Fresno	California
United States	Saint Mary's Healthcare	Grand Rapids	Michigan
United States	Pennsylvania State University, Hershey Medical Center	Hershey	Pennsylvania
United States	Methodist Neurological Institute	Houston	Texas
United States	Indiana University (Regenstrief Health Center)	Indianapolis	Indiana
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of Kentucky Medical Center	Lexington	Kentucky
United States	Bryan LGH Medical Center (University of Nebraska)	Lincoln	Nebraska
United States	Loma Linda University School of Medicine (CA)	Loma Linda	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	University of California, Los Angeles	Los Angeles	California
United States	University of Miami School of Medicine	Miami	Florida
United States	Hennepin County Medical Center (Berman Center)	Minneapolis	Minnesota
United States	Vanderbilt University	Nashville	Tennessee
United States	Hospital for Special Care	New Britain	Connecticut
United States	UMDNJ- Robert Wood Johnson School of Medicine	New Brunswick	New Jersey
United States	Beth Israel Medical Center (NY)	New York	New York
United States	Columbia University	New York	New York
United States	Cornell Medical Center	New York	New York
United States	University of California, Irvine - MDA ALS Neuromuscular Center	Orange	California
United States	Drexel University College of Medicine (Hahnemann Campus)	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Phoenix Neurological Associates	Phoenix	Arizona
United States	Allegheny Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Clinic (Providence Clinic)	Portland	Oregon
United States	University of Utah Health Sciences Center	Salt Lake City	Utah
United States	California Pacific Medical Center	San Francisco	California
United States	University of California, San Francisco	San Francisco	California
United States	St. Louis University	St. Louis	Missouri
United States	Washington University	St. Louis	Missouri
United States	SUNY Upstate Medical University	Syracuse	New York
United States	George Washington University	Washington	District of Columbia
United States	Wake Forest University School of Medicine	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Institute of Neurological Disorders and Stroke (NINDS)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival	Survival is presented as median day of survival for each group. Survival is defined as time to death, tracheostomy or the initiation of permanent assisted ventilation (PAV).	From date of randomization until date of death, tracheostomy, or the initiation of permanent assisted ventilation (PAV). This was assessed at time of each participant's drug discontinuation and every 2 months thereafter for the life of the study (6 yrs)	No
Primary	Change From Baseline in ALS Functional Rating Scale, Revised (ALSFRS-R) at One Year	Amyotrophic Lateral Sclerosis Functional Rating Scale, Revised (ALSFRS-R) is a quickly administered (five minute) ordinal rating scale used to determine patients' assessment of their capability and independence in 12 functional activities/questions. The 12 functional activities/questions are rated on a scale of 0 to 4 for a total scoring range of 0-48, with 48 representing optimal function. All 12 activities are relevant in ALS.; This outcome measure calculation is based on measurements every 8 weeks from the Baseline Visit up until one year.	Every 8 weeks for one year	No
Secondary	Change in % Vital Capacity From Screening to One Year	Vital Capacity is measured as the percent predicted per subject based on age, gender, and height, and is performed as a Slow Vital Capacity.; This outcome measure calculation is based on measurements every 12 weeks from the Baseline Visit up until one year.	Every 12 weeks for one Year	No
Secondary	Change From Baseline in Evaluation of Multiple Upper Extremity Muscles Using Hand Held Dynamometry at One Year	Hand-held Dynamometry (HHD) is used to evaluate muscle strength. Six proximal muscle groups were examined bilaterally in both upper and lower extremities (shoulder flexion, elbow flexion, elbow extension, hip flexion, knee flexion, and knee extension). In addition, wrist extension, first dorsal interosseous contraction and ankle dorsiflexion were measured bilaterally.; HHD analysis was performed using Percent Change from Baseline. Each subject's baseline strength value for each muscle group is considered 100%. During successive visits strength for each muscle group was measured using HHD and was calculated as a percentage of the initial baseline value recorded. Upper extremity and lower extremity values were calculated as the sum of all tests for that extremity to create one megascore for upper and one megascore for lower extremity muscles.; This outcome measure calculation is based on measurements every 12 weeks from the Baseline Visit up until one year.	Every 12 weeks for one Year	No
Secondary	Change From Baseline in the ALS-Specific Quality of Life Scale (ALSQOL) at One Year	The ALS-Specific Quality of Life Scale (ALSQOL). was developed, tested, and validated in subjects with ALS, and is not a health-related quality of life scale. The scale consists of 59 questions that ask about severity of the symptoms of ALS, mood and affect, intimacy, and social issues. Each question for the ALSQOL is scored from 0-10. With 59 questions, total score ranges from 0-590 with scores simply added, with 590 representing highest quality of life. However since 10 is maximally weighted towards negative values on some questions and positive values on others, the following questions must have results transposed (Simply reverse the scale, for instance 10=0 and 0=10) prior to analysis: 1-10, 11, 16, 19, 24, 26, 28, 32, 35, 36, 38, and 41. Optional items are 50, 53, 56, and 59. These questions are not included on any scale or in any quantitative analyses.; This outcome measure calculation is based on measurements every 12 weeks from the Baseline Visit up until one year.	Every 12 weeks for one Year	No
Secondary	Change From Baseline in Evaluation of Multiple Lower Extremity Muscles Using Hand Held Dynamometry at One Year	Hand-held Dynamometry (HHD) is used to evaluate muscle strength. Six proximal muscle groups were examined bilaterally in both upper and lower extremities (shoulder flexion, elbow flexion, elbow extension, hip flexion, knee flexion, and knee extension). In addition, wrist extension, first dorsal interosseous contraction and ankle dorsiflexion were measured bilaterally.; HHD analysis was performed using Percent Change from Baseline. Each subject's baseline strength value for each muscle group is considered 100%. During successive visits strength for each muscle group was measured using HHD and was calculated as a percentage of the initial baseline value recorded. Upper extremity and lower extremity values were calculated as the sum of all tests for that extremity to create one megascore for upper and one megascore for lower extremity muscles.; This outcome measure calculation is based on measurements every 12 weeks from the Baseline Visit up until one year.	Every 12 weeks for one Year	No

External Links

•   Northeast ALS Consortium website