Clinical Trial Ceftriaxone in Subjects With ALS
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ClinicalTrials.gov Identifier: NCT00349622 |
Recruitment Status
:
Completed
First Posted
: July 7, 2006
Results First Posted
: April 1, 2014
Last Update Posted
: April 21, 2014
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Amyotrophic Lateral Sclerosis ALS | Drug: ceftriaxone Other: placebo | Phase 3 |
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.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 513 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Double (Participant, Investigator) |
Primary Purpose: | Treatment |
Official Title: | Clinical Trial Ceftriaxone in Subjects With Amyotrophic Lateral Sclerosis (ALS) |
Study Start Date : | July 2006 |
Actual Primary Completion Date : | November 2012 |
Actual Study Completion Date : | November 2012 |

Arm | Intervention/treatment |
---|---|
Active Comparator: 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. |
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. |
Placebo Comparator: 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. |
Other: placebo
an inactive substance
|
- Survival [ Time Frame: 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 [ Time Frame: 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.
- Change in % Vital Capacity From Screening to One Year [ Time Frame: 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 Upper Extremity Muscles Using Hand Held Dynamometry at One Year [ Time Frame: 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 the ALS-Specific Quality of Life Scale (ALSQOL) at One Year [ Time Frame: 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 From Baseline in Evaluation of Multiple Lower Extremity Muscles Using Hand Held Dynamometry at One Year [ Time Frame: 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.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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).

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00349622

United States, Arizona | |
Phoenix Neurological Associates | |
Phoenix, Arizona, United States, 85018 | |
United States, California | |
University of California, Davis | |
Davis, California, United States, 95819 | |
University of California, San Francisco- Fresno | |
Fresno, California, United States, 93701 | |
Loma Linda University School of Medicine (CA) | |
Loma Linda, California, United States, 92354 | |
Cedars-Sinai Medical Center | |
Los Angeles, California, United States, 90048 | |
University of California, Los Angeles | |
Los Angeles, California, United States, 90095 | |
University of California, Irvine - MDA ALS Neuromuscular Center | |
Orange, California, United States, 92868 | |
California Pacific Medical Center | |
San Francisco, California, United States, 94115 | |
University of California, San Francisco | |
San Francisco, California, United States, 94117 | |
United States, Colorado | |
University of Colorado Health Sciences Center | |
Aurora, Colorado, United States, 80045 | |
United States, Connecticut | |
Hospital for Special Care | |
New Britain, Connecticut, United States, 06053 | |
United States, District of Columbia | |
George Washington University | |
Washington, District of Columbia, United States, 20037 | |
United States, Florida | |
Mayo Clinic Jacksonville | |
Jacksonville, Florida, United States, 32224 | |
University of Miami School of Medicine | |
Miami, Florida, United States, 33136 | |
United States, Georgia | |
ALS Center at Emory University | |
Atlanta, Georgia, United States, 30322 | |
Medical College of Georgia | |
Augusta, Georgia, United States, 30912 | |
United States, Illinois | |
Northwestern University Medical School | |
Chicago, Illinois, United States, 60611 | |
United States, Indiana | |
Indiana University (Regenstrief Health Center) | |
Indianapolis, Indiana, United States, 46202 | |
United States, Kansas | |
University of Kansas Medical Center | |
Kansas City, Kansas, United States, 66161 | |
United States, Kentucky | |
University of Kentucky Medical Center | |
Lexington, Kentucky, United States, 40536 | |
United States, Massachusetts | |
Massachusetts General Hospital | |
Boston, Massachusetts, United States, 02114 | |
Lahey Clinic | |
Burlington, Massachusetts, United States, 01805 | |
United States, Michigan | |
Henry Ford Health System | |
Detroit, Michigan, United States, 48202 | |
Saint Mary's Healthcare | |
Grand Rapids, Michigan, United States, 49503 | |
United States, Minnesota | |
Hennepin County Medical Center (Berman Center) | |
Minneapolis, Minnesota, United States, 55404 | |
United States, Missouri | |
St. Louis University | |
St. Louis, Missouri, United States, 63104 | |
Washington University | |
St. Louis, Missouri, United States, 63110 | |
United States, Nebraska | |
Bryan LGH Medical Center (University of Nebraska) | |
Lincoln, Nebraska, United States, 68506 | |
United States, New Jersey | |
UMDNJ- Robert Wood Johnson School of Medicine | |
New Brunswick, New Jersey, United States, 08901 | |
United States, New York | |
Albany Medical Center | |
Albany, New York, United States, 12208 | |
Beth Israel Medical Center (NY) | |
New York, New York, United States, 10003 | |
Cornell Medical Center | |
New York, New York, United States, 10021 | |
Columbia University | |
New York, New York, United States, 10032 | |
SUNY Upstate Medical University | |
Syracuse, New York, United States, 13210 | |
United States, North Carolina | |
Carolinas Medical Center | |
Charlotte, North Carolina, United States, 28203 | |
Wake Forest University School of Medicine | |
Winston-Salem, North Carolina, United States, 27157 | |
United States, Ohio | |
The Cleveland Clinic Foundation | |
Cleveland, Ohio, United States, 44195 | |
Ohio State University | |
Columbus, Ohio, United States, 43210 | |
United States, Oregon | |
Oregon Clinic (Providence Clinic) | |
Portland, Oregon, United States, 97213 | |
United States, Pennsylvania | |
Pennsylvania State University, Hershey Medical Center | |
Hershey, Pennsylvania, United States, 17033 | |
Drexel University College of Medicine (Hahnemann Campus) | |
Philadelphia, Pennsylvania, United States, 19107 | |
University of Pennsylvania | |
Philadelphia, Pennsylvania, United States, 19107 | |
Allegheny Hospital | |
Pittsburgh, Pennsylvania, United States, 15212 | |
University of Pittsburgh | |
Pittsburgh, Pennsylvania, United States, 15213 | |
United States, South Carolina | |
Medical University of South Carolina | |
Charleston, South Carolina, United States, 29403 | |
United States, Tennessee | |
Vanderbilt University | |
Nashville, Tennessee, United States, 37232 | |
United States, Texas | |
Texas Neurology | |
Dallas, Texas, United States, 75214 | |
Methodist Neurological Institute | |
Houston, Texas, United States, 77030 | |
United States, Utah | |
University of Utah Health Sciences Center | |
Salt Lake City, Utah, United States, 84132 | |
United States, Virginia | |
University of Virginia | |
Charlottesville, Virginia, United States, 22908 | |
Canada, Alberta | |
University of Calgary | |
Calgary, Alberta, Canada, T2N 4Z6 | |
Univeristy of Alberta ALS Clinic | |
Edmonton, Alberta, Canada, T6G 2B7 | |
Canada, Nova Scotia | |
Dalhousie University | |
Halifax, Nova Scotia, Canada | |
Canada, Ontario | |
London Health Sciences Center, University Campus | |
London, Ontario, Canada | |
University of Toronto | |
Toronto, Ontario, Canada | |
Canada, Quebec | |
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 |
Principal Investigator: | Merit Cudkowicz, MD, MSc. | Associate Professor of Neurology, Harvard Medical School, Massachusetts General Hospital |
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Merit E. Cudkowicz, MD, Professor of Neurology, Massachusetts General Hospital |
ClinicalTrials.gov Identifier: | NCT00349622 History of Changes |
Other Study ID Numbers: |
U01NS049640-02 ( U.S. NIH Grant/Contract ) NINDS ( Other Identifier: NINDS ) NINDS CRC ( Other Identifier: NINDS Clinical Research Collaboration ) |
First Posted: | July 7, 2006 Key Record Dates |
Results First Posted: | April 1, 2014 |
Last Update Posted: | April 21, 2014 |
Last Verified: | April 2014 |
Keywords provided by Merit E. Cudkowicz, MD, Massachusetts General Hospital:
amyotrophic lateral sclerosis ALS ceftriaxone cephalosporin antibiotic motor neurons |
Additional relevant MeSH terms:
Sclerosis Motor Neuron Disease Amyotrophic Lateral Sclerosis Pathologic Processes Neurodegenerative Diseases Nervous System Diseases Neuromuscular Diseases Spinal Cord Diseases |
Central Nervous System Diseases TDP-43 Proteinopathies Proteostasis Deficiencies Metabolic Diseases Ceftriaxone Cephalosporins Anti-Bacterial Agents Anti-Infective Agents |