Clinical Trial Ceftriaxone in Subjects With ALS

NCT ID: NCT00349622

Last Updated: 2014-04-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 513 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-07-31
• Study Completion Date: 2012-11-30

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.

Conditions

Amyotrophic Lateral Sclerosis; ALS

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

ceftriaxone

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

an inactive substance

Interventions

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.

Intervention Type: DRUG

placebo

an inactive substance

Intervention Type: OTHER

Eligibility 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Merit E. Cudkowicz, MD

Professor of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Merit Cudkowicz, MD, MSc.

Role: PRINCIPAL_INVESTIGATOR

Associate Professor of Neurology, Harvard Medical School, Massachusetts General Hospital

Locations

Phoenix Neurological Associates

Phoenix, Arizona, United States

University of California, Davis

Davis, California, United States

University of California, San Francisco- Fresno

Fresno, California, 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 California, Irvine - MDA ALS Neuromuscular Center

Orange, California, United States

California Pacific Medical Center

San Francisco, California, United States

University of California, San Francisco

San Francisco, California, United States

University of Colorado Health Sciences Center

Aurora, Colorado, United States

Hospital for Special Care

New Britain, Connecticut, United States

George Washington University

Washington D.C., District of Columbia, United States

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

University of Miami School of Medicine

Miami, Florida, United States

ALS Center at Emory University

Atlanta, Georgia, United States

Medical College of Georgia

Augusta, Georgia, United States

Northwestern University Medical School

Chicago, Illinois, United States

Indiana University (Regenstrief Health Center)

Indianapolis, Indiana, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

University of Kentucky Medical Center

Lexington, Kentucky, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Lahey Clinic

Burlington, Massachusetts, United States

Henry Ford Health System

Detroit, Michigan, United States

Saint Mary's Healthcare

Grand Rapids, Michigan, United States

Hennepin County Medical Center (Berman Center)

Minneapolis, Minnesota, United States

St. Louis University

St Louis, Missouri, United States

Washington 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

Albany Medical Center

Albany, New York, United States

Beth Israel Medical Center (NY)

New York, New York, United States

Cornell Medical Center

New York, New York, United States

Columbia University

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

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Oregon Clinic (Providence Clinic)

Portland, Oregon, 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 Pennsylvania

Philadelphia, Pennsylvania, United States

Allegheny Hospital

Pittsburgh, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Vanderbilt University

Nashville, Tennessee, United States

Texas Neurology

Dallas, Texas, United States

Methodist Neurological Institute

Houston, Texas, United States

University of Utah Health Sciences Center

Salt Lake City, Utah, United States

University of Virginia

Charlottesville, Virginia, United States

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

University of Toronto

Toronto, 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

Québec, Quebec, Canada

Countries

United States; Canada

References

McDonnell E, Schoenfeld D, Paganoni S, Atassi N. Causal inference methods to study gastric tube use in amyotrophic lateral sclerosis. Neurology. 2017 Oct 3;89(14):1483-1489. doi: 10.1212/WNL.0000000000004534. Epub 2017 Sep 1.

Reference Type: DERIVED

PMID: 28864675 (View on PubMed)

Cudkowicz ME, Titus S, Kearney M, Yu H, Sherman A, Schoenfeld D, Hayden D, Shui A, Brooks B, Conwit R, Felsenstein D, Greenblatt DJ, Keroack M, Kissel JT, Miller R, Rosenfeld J, Rothstein JD, Simpson E, Tolkoff-Rubin N, Zinman L, Shefner JM; Ceftriaxone Study Investigators. Safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis: a multi-stage, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2014 Nov;13(11):1083-1091. doi: 10.1016/S1474-4422(14)70222-4. Epub 2014 Oct 5.

Reference Type: DERIVED

PMID: 25297012 (View on PubMed)

Berry JD, Shefner JM, Conwit R, Schoenfeld D, Keroack M, Felsenstein D, Krivickas L, David WS, Vriesendorp F, Pestronk A, Caress JB, Katz J, Simpson E, Rosenfeld J, Pascuzzi R, Glass J, Rezania K, Rothstein JD, Greenblatt DJ, Cudkowicz ME; Northeast ALS Consortium. Design and initial results of a multi-phase randomized trial of ceftriaxone in amyotrophic lateral sclerosis. PLoS One. 2013 Apr 17;8(4):e61177. doi: 10.1371/journal.pone.0061177. Print 2013.

Reference Type: DERIVED

PMID: 23613806 (View on PubMed)

Related Links

http://www.alsconsortium.org

Northeast ALS Consortium website

Other Identifiers

NINDS

Identifier Type: OTHER

Identifier Source: secondary_id

U01NS049640-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NINDS CRC

Identifier Type: OTHER

Identifier Source: secondary_id

U01NS049640-02

Identifier Type: NIH

Identifier Source: org_study_id

View Link