Clinical trial NCT00349622: Clinical Trial Ceftriaxone in Subjects With ALS
Official title: Clinical Trial Ceftriaxone in Subjects With Amyotrophic Lateral Sclerosis (ALS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Amyotrophic Lateral Sclerosis
ALS
Keywords: amyotrophic lateral sclerosis
ALS
ceftriaxone
cephalosporin antibiotic
motor neurons
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2006-07-07
Enrollment: 513
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Survival
timeFrame: 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)
measure: Change From Baseline in ALS Functional Rating Scale, Revised (ALSFRS-R) at One Year
timeFrame: Every 8 weeks for one year
Secondary outcomes:
measure: Change in % Vital Capacity From Screening to One Year
timeFrame: Every 12 weeks for one Year
measure: Change From Baseline in Evaluation of Multiple Upper Extremity Muscles Using Hand Held Dynamometry at One Year
timeFrame: Every 12 weeks for one Year
measure: Change From Baseline in the ALS-Specific Quality of Life Scale (ALSQOL) at One Year
timeFrame: Every 12 weeks for one Year
measure: Change From Baseline in Evaluation of Multiple Lower Extremity Muscles Using Hand Held Dynamometry at One Year
timeFrame: Every 12 weeks for one Year
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Neurological Associates
state: Arizona
city: Davis
country: United States
facility: University of California, Davis
state: California
city: Fresno
country: United States
facility: University of California, San Francisco- Fresno
state: California
city: Loma Linda
country: United States
facility: Loma Linda University School of Medicine (CA)
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Orange
country: United States
facility: University of California, Irvine - MDA ALS Neuromuscular Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: New Britain
country: United States
facility: Hospital for Special Care
state: Connecticut
city: Washington
country: United States
facility: George Washington University
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Miami
country: United States
facility: University of Miami School of Medicine
state: Florida
city: Atlanta
country: United States
facility: ALS Center at Emory University
state: Georgia
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Medical School
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University (Regenstrief Health Center)
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Clinic
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Grand Rapids
country: United States
facility: Saint Mary's Healthcare
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center (Berman Center)
state: Minnesota
city: St. Louis
country: United States
facility: St. Louis University
state: Missouri
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Lincoln
country: United States
facility: Bryan LGH Medical Center (University of Nebraska)
state: Nebraska
city: New Brunswick
country: United States
facility: UMDNJ- Robert Wood Johnson School of Medicine
state: New Jersey
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center (NY)
state: New York
city: New York
country: United States
facility: Cornell Medical Center
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Portland
country: United States
facility: Oregon Clinic (Providence Clinic)
state: Oregon
city: Hershey
country: United States
facility: Pennsylvania State University, Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel University College of Medicine (Hahnemann Campus)
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Dallas
country: United States
facility: Texas Neurology
state: Texas
city: Houston
country: United States
facility: Methodist Neurological Institute
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health Sciences Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Univeristy of Alberta ALS Clinic
state: Alberta
city: Halifax
country: Canada
facility: Dalhousie University
state: Nova Scotia
city: London
country: Canada
facility: London Health Sciences Center, University Campus
state: Ontario
city: Toronto
country: Canada
facility: University of Toronto
state: Ontario
city: Montreal
country: Canada
facility: CHUM (Centre Hospitalier de l'Université de Montréal), Notre-Dame Hospital
state: Quebec
city: Montreal
country: Canada
facility: Montreal Neurological Institute (McGill University)
state: Quebec
city: Quebec City
country: Canada
facility: Laval University
state: Quebec
Study officials:
affiliation: Associate Professor of Neurology, Harvard Medical School, Massachusetts General Hospital
name: Merit Cudkowicz, MD, MSc.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.