Official Title: “Clinical Trial Ceftriaxone in Subjects With Amyotrophic Lateral Sclerosis (ALS)”

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

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: June 2011

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 or placebo for at least 12 months. The study consists of three stages. The first stage will find out if ceftriaxone enters the cerebrospinal fluid (fluid that surrounds the spinal cord, also called CSF) in amounts that are high enough to be of possible benefit. The second stage will look at the safety and side effects of the study drug when taken daily for 16 weeks. The third stage will try to find out whether the study drug helps people with ALS live longer. Sixty participants will take part in stages 1 and 2 and will continue on to stage 3. An additional 540 participants will take part in stage 3.

Duration of the study for participants varies from 1 to 5 years, and may include up to 70 site visits.

Intervention(s) in this Clinical Trial

• Drug: ceftriaxone
  • Participants will be randomly assigned to receive treatment with ceftriaxone or placebo for at least 12 months. 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

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Ceftriaxone
• Placebo Comparator: 2

Primary Measures

• Survival.
  • Time Frame: duration of the study
    Safety Issue?: No

Secondary Measures

• ALSFRS-R
  • Time Frame: duration of the study
    Safety Issue?: No
• vital capacity
  • Time Frame: duration of the study
    Safety Issue?: No
• evaluation of multiple upper extremity muscles using hand held dynamometry
  • Time Frame: duration of the study
    Safety Issue?: No
• quality of life
  • Time Frame: duration of the study
    Safety Issue?: No
• long-term safety and tolerability of ceftriaxone.
  • Time Frame: duration of the study
    Safety Issue?: 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).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Massachusetts General Hospital

Overall Clinical Trial Officials and Contacts

Merit Cudkowicz, MD, MSc. Principal Investigator Associate Professor of Neurology, Harvard Medical School, Massachusetts General Hospital  

Information obtained from ClinicalTrials.gov on November 19, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00349622

Study ID Number: U01NS049640-02

ClinicalTrials.gov Identifier: NCT00349622

Health Authority: United States: Food and Drug Administration

Northeast ALS Consortium website