NCT00349622

Brief Summary

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

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
513

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Jul 2006

Longer than P75 for phase_3

Geographic Reach
2 countries

58 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2006

Completed
4 days until next milestone

First Submitted

Initial submission to the registry

July 5, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 7, 2006

Completed
6.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2012

Completed
1.4 years until next milestone

Results Posted

Study results publicly available

April 1, 2014

Completed
Last Updated

April 21, 2014

Status Verified

April 1, 2014

Enrollment Period

6.3 years

First QC Date

July 5, 2006

Results QC Date

October 23, 2013

Last Update Submit

April 1, 2014

Conditions

Keywords

amyotrophic lateral sclerosisALSceftriaxonecephalosporin antibioticmotor neurons

Outcome Measures

Primary Outcomes (2)

  • Survival

    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).

    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)

  • Change From Baseline in ALS Functional Rating Scale, Revised (ALSFRS-R) at One Year

    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.

    Every 8 weeks for one year

Secondary Outcomes (4)

  • Change in % Vital Capacity From Screening to One Year

    Every 12 weeks for one Year

  • Change From Baseline in Evaluation of Multiple Upper Extremity Muscles Using Hand Held Dynamometry at One Year

    Every 12 weeks for one Year

  • Change From Baseline in the ALS-Specific Quality of Life Scale (ALSQOL) at One Year

    Every 12 weeks for one Year

  • Change From Baseline in Evaluation of Multiple Lower Extremity Muscles Using Hand Held Dynamometry at One Year

    Every 12 weeks for one Year

Study Arms (2)

Ceftriaxone

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Interventions

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.

Ceftriaxone
placeboOTHER

an inactive substance

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (58)

Phoenix Neurological Associates

Phoenix, Arizona, 85018, United States

Location

University of California, Davis

Davis, California, 95819, United States

Location

University of California, San Francisco- Fresno

Fresno, California, 93701, United States

Location

Loma Linda University School of Medicine (CA)

Loma Linda, California, 92354, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

University of California, Irvine - MDA ALS Neuromuscular Center

Orange, California, 92868, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

University of California, San Francisco

San Francisco, California, 94117, United States

Location

University of Colorado Health Sciences Center

Aurora, Colorado, 80045, United States

Location

Hospital for Special Care

New Britain, Connecticut, 06053, United States

Location

George Washington University

Washington D.C., District of Columbia, 20037, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of Miami School of Medicine

Miami, Florida, 33136, United States

Location

ALS Center at Emory University

Atlanta, Georgia, 30322, United States

Location

Medical College of Georgia

Augusta, Georgia, 30912, United States

Location

Northwestern University Medical School

Chicago, Illinois, 60611, United States

Location

Indiana University (Regenstrief Health Center)

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66161, United States

Location

University of Kentucky Medical Center

Lexington, Kentucky, 40536, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Lahey Clinic

Burlington, Massachusetts, 01805, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Saint Mary's Healthcare

Grand Rapids, Michigan, 49503, United States

Location

Hennepin County Medical Center (Berman Center)

Minneapolis, Minnesota, 55404, United States

Location

St. Louis University

St Louis, Missouri, 63104, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Bryan LGH Medical Center (University of Nebraska)

Lincoln, Nebraska, 68506, United States

Location

UMDNJ- Robert Wood Johnson School of Medicine

New Brunswick, New Jersey, 08901, United States

Location

Albany Medical Center

Albany, New York, 12208, United States

Location

Beth Israel Medical Center (NY)

New York, New York, 10003, United States

Location

Cornell Medical Center

New York, New York, 10021, United States

Location

Columbia University

New York, New York, 10032, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28203, United States

Location

Wake Forest University School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Oregon Clinic (Providence Clinic)

Portland, Oregon, 97213, United States

Location

Pennsylvania State University, Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Drexel University College of Medicine (Hahnemann Campus)

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

Location

Allegheny Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29403, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Texas Neurology

Dallas, Texas, 75214, United States

Location

Methodist Neurological Institute

Houston, Texas, 77030, United States

Location

University of Utah Health Sciences Center

Salt Lake City, Utah, 84132, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

Univeristy of Alberta ALS Clinic

Edmonton, Alberta, T6G 2B7, Canada

Location

Dalhousie University

Halifax, Nova Scotia, Canada

Location

London Health Sciences Center, University Campus

London, Ontario, Canada

Location

University of Toronto

Toronto, Ontario, Canada

Location

CHUM (Centre Hospitalier de l'Université de Montréal), Notre-Dame Hospital

Montreal, Quebec, Canada

Location

Montreal Neurological Institute (McGill University)

Montreal, Quebec, Canada

Location

Laval University

Québec, Quebec, Canada

Location

Related Publications (3)

  • 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.

  • 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.

  • 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.

Related Links

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Ceftriaxone

Condition Hierarchy (Ancestors)

Spinal Cord DiseasesCentral Nervous System DiseasesNervous System DiseasesMotor Neuron DiseaseNeurodegenerative DiseasesTDP-43 ProteinopathiesNeuromuscular DiseasesProteostasis DeficienciesMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

CefotaximeCephacetrileCephalosporinsbeta-LactamsLactamsAmidesOrganic ChemicalsThiazinesSulfur CompoundsHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Results Point of Contact

Title
Merit Cudkowicz
Organization
MGH

Study Officials

  • Merit Cudkowicz, MD, MSc.

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

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Neurology

Study Record Dates

First Submitted

July 5, 2006

First Posted

July 7, 2006

Study Start

July 1, 2006

Primary Completion

November 1, 2012

Study Completion

November 1, 2012

Last Updated

April 21, 2014

Results First Posted

April 1, 2014

Record last verified: 2014-04

Locations