Clinical Trial Ceftriaxone in Subjects With ALS

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Merit E. Cudkowicz, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00349622
First received: July 5, 2006
Last updated: April 1, 2014
Last verified: April 2014
  Purpose

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


Condition Intervention Phase
Amyotrophic Lateral Sclerosis
ALS
Drug: ceftriaxone
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Clinical Trial Ceftriaxone in Subjects With Amyotrophic Lateral Sclerosis (ALS)

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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:
  • Change in % Vital Capacity From Screening to One Year [ Time Frame: Every 12 weeks for one Year ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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.



Enrollment: 513
Study Start Date: July 2006
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00349622

  Hide Study Locations
Locations
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
University of California, Los Angeles
Los Angeles, California, United States, 90095
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
University of California, Irvine - MDA ALS Neuromuscular Center
Orange, California, United States, 92868
University of California, San Francisco
San Francisco, California, United States, 94117
California Pacific Medical Center
San Francisco, California, United States, 94115
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
Washington University
St. Louis, Missouri, United States, 63110
St. Louis University
St. Louis, Missouri, United States, 63104
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
Cornell Medical Center
New York, New York, United States, 10021
Columbia University
New York, New York, United States, 10032
Beth Israel Medical Center (NY)
New York, New York, United States, 10003
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
Montreal Neurological Institute (McGill University)
Montreal, Quebec, Canada
CHUM (Centre Hospitalier de l'Université de Montréal), Notre-Dame Hospital
Montreal, Quebec, Canada
Laval University
Quebec City, Quebec, Canada
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Merit Cudkowicz, MD, MSc. Associate Professor of Neurology, Harvard Medical School, Massachusetts General Hospital
  More Information

Additional Information:
No publications provided by Massachusetts General Hospital

Additional 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, NINDS, U01NS049640-02, NINDS CRC
Study First Received: July 5, 2006
Results First Received: October 23, 2013
Last Updated: April 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
amyotrophic lateral sclerosis
ALS
ceftriaxone
cephalosporin antibiotic
motor neurons

Additional relevant MeSH terms:
Amyotrophic Lateral Sclerosis
Sclerosis
Motor Neuron Disease
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
TDP-43 Proteinopathies
Neuromuscular Diseases
Proteostasis Deficiencies
Metabolic Diseases
Pathologic Processes
Ceftriaxone
Cephalosporins
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 19, 2014