Clinical Trial Ceftriaxone in Subjects With ALS
- Conditions
- Amyotrophic Lateral SclerosisALS
- Interventions
- Other: placebo
- Registration Number
- NCT00349622
- Lead Sponsor
- Massachusetts General Hospital
- Brief Summary
The purpose of the study is to evaluate the safety and efficacy of ceftriaxone treatment in amyotrophic lateral sclerosis (ALS).
- Detailed 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 & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 513
- 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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo placebo One third of participants were assigned to placebo, or an inactive substance. This is a blinded study, so neither participants nor study staff will know which treatment a participant is receiving. Pediatric multivitamin solution was used as the placebo in this study and was administered intravenously via a central venous catheter twice a day. Ceftriaxone ceftriaxone Two thirds of participants were assigned to 4 grams of ceftriaxone per day. This is a blinded study, so neither participants nor study staff will know which treatment a participant is receiving. Ceftriaxone is a cephalosporin antibiotic and was administered intravenously via a central venous catheter twice a day.
- Primary Outcome Measures
Name Time Method Survival 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) 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).
Change From Baseline in ALS Functional Rating Scale, Revised (ALSFRS-R) at One Year Every 8 weeks for 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.
- Secondary Outcome Measures
Name Time Method Change From Baseline in the ALS-Specific Quality of Life Scale (ALSQOL) at One Year Every 12 weeks for 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.Change in % Vital Capacity From Screening to One Year Every 12 weeks for 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.Change From Baseline in Evaluation of Multiple Lower Extremity Muscles Using Hand Held Dynamometry at One Year Every 12 weeks for 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.Change From Baseline in Evaluation of Multiple Upper Extremity Muscles Using Hand Held Dynamometry at One Year Every 12 weeks for 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.
Trial Locations
- Locations (58)
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Lahey Clinic
🇺🇸Burlington, Massachusetts, 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
Medical College of Georgia
🇺🇸Augusta, Georgia, United States
University of California, San Francisco- Fresno
🇺🇸Fresno, California, United States
Allegheny Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
University of Calgary
🇨🇦Calgary, Alberta, Canada
Laval University
🇨🇦Quebec City, Quebec, Canada
Montreal Neurological Institute (McGill University)
🇨🇦Montreal, Quebec, Canada
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
London Health Sciences Center, University Campus
🇨🇦London, Ontario, Canada
Texas Neurology
🇺🇸Dallas, Texas, United States
CHUM (Centre Hospitalier de l'Université de Montréal), Notre-Dame Hospital
🇨🇦Montreal, Quebec, Canada
Univeristy of Alberta ALS Clinic
🇨🇦Edmonton, Alberta, Canada
University of Toronto
🇨🇦Toronto, Ontario, Canada
Dalhousie University
🇨🇦Halifax, Nova Scotia, Canada
Phoenix Neurological Associates
🇺🇸Phoenix, Arizona, United States
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Oregon Clinic (Providence Clinic)
🇺🇸Portland, Oregon, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
University of California, Davis
🇺🇸Davis, California, United States
Loma Linda University School of Medicine (CA)
🇺🇸Loma Linda, California, United States
University of California, Irvine - MDA ALS Neuromuscular Center
🇺🇸Orange, California, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
University of Colorado Health Sciences Center
🇺🇸Aurora, Colorado, United States
University of Miami School of Medicine
🇺🇸Miami, Florida, United States
Mayo Clinic Jacksonville
🇺🇸Jacksonville, Florida, United States
Hospital for Special Care
🇺🇸New Britain, Connecticut, United States
George Washington University
🇺🇸Washington, District of Columbia, United States
Indiana University (Regenstrief Health Center)
🇺🇸Indianapolis, Indiana, United States
University of Kentucky Medical Center
🇺🇸Lexington, Kentucky, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Washington University
🇺🇸St. Louis, Missouri, United States
Hennepin County Medical Center (Berman Center)
🇺🇸Minneapolis, Minnesota, United States
St. Louis University
🇺🇸St. Louis, Missouri, United States
Bryan LGH Medical Center (University of Nebraska)
🇺🇸Lincoln, Nebraska, United States
UMDNJ- Robert Wood Johnson School of Medicine
🇺🇸New Brunswick, New Jersey, United States
Columbia University
🇺🇸New York, New York, United States
Cornell Medical Center
🇺🇸New York, New York, United States
Beth Israel Medical Center (NY)
🇺🇸New York, New York, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Wake Forest University School of Medicine
🇺🇸Winston-Salem, North Carolina, United States
Pennsylvania State University, Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Drexel University College of Medicine (Hahnemann Campus)
🇺🇸Philadelphia, Pennsylvania, United States
University of Utah Health Sciences Center
🇺🇸Salt Lake City, Utah, United States
Methodist Neurological Institute
🇺🇸Houston, Texas, United States
ALS Center at Emory University
🇺🇸Atlanta, Georgia, United States
Saint Mary's Healthcare
🇺🇸Grand Rapids, Michigan, United States
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Albany Medical Center
🇺🇸Albany, New York, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States