Minocycline to Treat Amyotrophic Lateral Sclerosis

NCT ID: NCT00047723

Last Updated: 2007-12-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-01-31

Study Completion Date

2007-01-31

Brief Summary

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The purpose of this trial is to test the safety, tolerability, and effectiveness of minocycline compared to placebo in patients with amyotrophic lateral sclerosis (ALS).

Detailed Description

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ALS is a progressive neurodegenerative disorder without cure or known treatment that significantly improves function. Loss of motor neurons in the brain and spinal cord of ALS patients causes the progressive symptoms. Laboratory studies have linked inducible nitric oxide synthase (iNOS) and caspase enzyme activation to motor nerve cell death in ALS. Minocycline-a medication currently approved by the FDA for treatment of bacterial infections-is a tetracycline antibiotic with high central nervous system penetration when taken orally. The drug inhibits the activity of iNOS and caspase enzymes.

Minocycline has been tested and shown to protect nerve cells in many scientific experiments. It reduces cell death and prolongs survival in animal models of ALS, stroke, trauma, Huntington's disease, and Parkinson's disease. It has been shown to be beneficial in many different animal experiments of ALS, conducted in Europe, Canada and the United States.

Minocycline has been tested in 2 preliminary human trials and has been shown to be safe in patients with ALS. It has been well tolerated in conjunction with riluzole (Rilutek), the only currently FDA-approved medication for ALS.

This trial is the final important step in determining whether minocycline improves the course of ALS. The principle objective of this clinical trial is to determine whether minocycline slows disease progression and helps maintain function in patients with ALS. This multi-center placebo-controlled study will select patients early in the course of ALS, when a neuroprotective therapy may be most beneficial. The study will measure change in function (as detected by ALSFRS-R scores), strength, pulmonary function, survival, and quality of life. Participants will undergo monthly outpatient evaluations and analysis of laboratory and adverse events. This is a 13-month study.

Conditions

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Amyotrophic Lateral Sclerosis

Keywords

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ALS amyotrophic lateral sclerosis minocycline

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Interventions

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minocycline

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* A clinical diagnosis of laboratory-supported probable, probable or definite ALS, according to modified EL Escorial criteria.
* FVC greater or equal to 75% of predicted.
* Onset of weakness within 3 years prior to enrollment.
* If patients are receiving riluzole they must be on a stable dose for at least the past thirty days.
* Women of childbearing age must be non-lactating and surgically sterile or using an effective method of birth control and have a negative pregnancy test (adequate birth control includes use of intra-uterine device or oral contraceptives plus a barrier method, e.g. condom, diaphragm).
* Willing and able to give signed informed consent that has been approved by your Institutional Review Board (IRB).

Exclusion Criteria

* Requirement for tracheotomy ventilation (or non-invasive ventilation \> 23 hours/day).
* Diagnosis of other neurodegenerative diseases (Parkinson's disease, Alzheimer's disease, etc).
* FVC \< 75% of predicted.
* A clinically significant history of unstable medical illness (unstable angina, advanced cancer, etc) over the last 30 days.
* History of renal disease (screening creatinine greater than 1.5).
* History of liver disease (screening alanine aminotransferase greater than 3 times the upper limit of normal).
* History of hematologic disease (screening white blood cell count less than 3,800/mm3).
* History of system lupus erythematosis (or screening ANA of 1:160 or greater).
* Treatment with any medications that may cause lupus-like symptoms within 4 weeks of baseline visit (e.g. procainamide, hydralazine).
* History of vestibular disease (excluding benign position vertigo).
* Pregnancy or lactation.
* Allergy to tetracycline antibiotics.
* Use of minocycline within thirty days of enrollment (baseline visit).
* Use of anti-epileptic medications other than gabapentin.
* Limited mental capacity rendering the subject unable to provide written informed consent or comply with evaluation procedures.
* History of recent alcohol or drug abuse or noncompliance with treatment or other experimental protocols.
* Use of any investigational drug within the past 30 days (Creatine, Vioxx, Celebrex, Topiramate).
* Women with the potential to become pregnant who are not practicing effective birth control.
Minimum Eligible Age

21 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role lead

Principal Investigators

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Paul H. Gordon, M.D.,

Role: PRINCIPAL_INVESTIGATOR

Associate Medical Director, Eleanor and Lou Gehrig MDA/ALS Center, Columbia University Medical Center

Locations

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Mayo Clinic

Scottsdale, Arizona, United States

Site Status

University of California, Irvine

Irvine, California, United States

Site Status

University of California Department of Neurology

Los Angeles, California, United States

Site Status

California Pacific Medical Center

San Francisco, California, United States

Site Status

Univ. of Colorado Health Sciences Center

Denver, Colorado, United States

Site Status

Mayo Clinic

Jacksonville, Florida, United States

Site Status

University of Illinois

Chicago, Illinois, United States

Site Status

Indiana University School of Medicine

Indianapolis, Indiana, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

Hennepin County Med Center

Minneapolis, Minnesota, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

UMDNJ/Robert Wood Johnson Medical Center

New Brunswick, New Jersey, United States

Site Status

University of New Mexico

Albuquerque, New Mexico, United States

Site Status

Columbia Unversity, Eleanor and Lou Gehrig MDA/ALS Center

New York, New York, United States

Site Status

Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

Wake Forest University

Winston-Salem, North Carolina, United States

Site Status

Metro Health Clinic

Cleveland, Ohio, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Drexel University College of Medicine, Hahnemann Campus

Philadelphia, Pennsylvania, United States

Site Status

University of Texas Southwestern

Dallas, Texas, United States

Site Status

Methodist Hospital

Houston, Texas, United States

Site Status

University of Texas Health Sciences Center

San Antonio, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

University of Vermont

Burlington, Vermont, United States

Site Status

Virginia Mason Medical Center

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Gordon PH, Moore DH, Miller RG, Florence JM, Verheijde JL, Doorish C, Hilton JF, Spitalny GM, MacArthur RB, Mitsumoto H, Neville HE, Boylan K, Mozaffar T, Belsh JM, Ravits J, Bedlack RS, Graves MC, McCluskey LF, Barohn RJ, Tandan R; Western ALS Study Group. Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial. Lancet Neurol. 2007 Dec;6(12):1045-53. doi: 10.1016/S1474-4422(07)70270-3. Epub 2007 Nov 5.

Reference Type RESULT
PMID: 17980667 (View on PubMed)

Other Identifiers

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R01NS045294

Identifier Type: NIH

Identifier Source: org_study_id

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