June 2009

The first two stages of the clinical trial of ceftriaxone in ALS have been completed.

The aim of stage 1 was to determine the pharmacokinetics (way the body absorbs, distributes, metabolizes and excretes a drug) of ceftriaxone at 2 grams and 4 grams per day.

The goal of stage 2 was to determine the 20-week safety and tolerability of ceftriaxone.

The efficacy portion of the study, called stage 3, has begun, and the study is now enrolling participants at approximately 50 U.S. and four Canadian centers. The aim of this portion of the study is to determine if ceftriaxone prolongs survival and/or slows decline in function.

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

It is known that nerve cells called motor neurons die in the brains and spinal cords of people with ALS. However, the cause of the 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 is an antibiotic (in a class known as “cephalosporins”) that is approved to treat certain types of infections. The investigators involved in this study are interested in studying ceftriaxone because the drug may also 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. 

This is a double-blind, placebo-controlled study. This means that neither participants nor investigators will know who is receiving ceftriaxone and who is not; and that a portion of the study participants will receive ceftriaxone, while another portion receive a placebo (an inert substance that looks like the study drug).

The third stage of the study, which opened in May 2009, will enroll 540 additional study participants.
 
Participants will have safety laboratory tests throughout the study and their strength and vital capacity will be tested at regular intervals.

Because ceftriaxone is in intravenous (IV) medication, participants will also have an intravenous catheter (called a "central venous catheter") placed in a vein in the chest, through which the study medication will be given.

The overall study principal investigator is Merit Cudkowicz, M.D., at Massachusetts GeneralHospital.  The co-principal Investigators are Swati Aggarwal, M.D., at Massachusetts GeneralHospital, and Jeremy Shefner, M.D., Ph.D., at SUNYUpstateMedicalCenter.

Inclusion Criteria

Participants must

• have ALS
• be at least 18 years old
• be medically able to undergo the study procedures
• have an FVC (forced vital capacity, a respiratory measurement) of at least 60 percent of normal
• have a caregiver who will be available to help with daily study medication administration
• live within a reasonable distance of the study site, because of the need for frequent site visits

Exclusion Criteria

Participants must not

• be taking any other experimental medications for ALS
• have a history of sensitivity to cephalosporin antibiotics (Ancef, Keflex, Ceclor, Ceftin, Lorabid, Suprax and Fortaz are examples)

This is not a complete list of eligibility criteria. Please contact your closest study site for detailed information regarding eligibility criteria and study participation.