Minocycline to Treat Amyotrophic Lateral Sclerosis

December 18, 2007 updated by: National Institute of Neurological Disorders and Stroke (NINDS)
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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment

400

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States
        • Mayo Clinic
    • California
      • Irvine, California, United States
        • University of California, Irvine
      • Los Angeles, California, United States
        • University of California Department of Neurology
      • San Francisco, California, United States
        • California Pacific Medical Center
    • Colorado
      • Denver, Colorado, United States
        • Univ. of Colorado Health Sciences Center
    • Florida
      • Jacksonville, Florida, United States
        • Mayo Clinic
    • Illinois
      • Chicago, Illinois, United States
        • University of Illinois
    • Indiana
      • Indianapolis, Indiana, United States
        • Indiana University School of Medicine
    • Iowa
      • Iowa City, Iowa, United States
        • University of Iowa
    • Kansas
      • Kansas City, Kansas, United States
        • University of Kansas Medical Center
    • Kentucky
      • Lexington, Kentucky, United States
        • University of Kentucky
    • Minnesota
      • Minneapolis, Minnesota, United States
        • University of Minnesota
      • Minneapolis, Minnesota, United States
        • Hennepin County Med Center
    • Missouri
      • St. Louis, Missouri, United States
        • Washington University
    • New Jersey
      • New Brunswick, New Jersey, United States
        • UMDNJ/Robert Wood Johnson Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States
        • University of New Mexico
    • New York
      • New York, New York, United States, 10032
        • Columbia Unversity, Eleanor and Lou Gehrig MDA/ALS Center
    • North Carolina
      • Charlotte, North Carolina, United States
        • Carolinas Medical Center
      • Durham, North Carolina, United States
        • Duke University
      • Winston- Salem, North Carolina, United States
        • Wake Forest University
    • Ohio
      • Cleveland, Ohio, United States
        • Metro Health Clinic
    • Oregon
      • Portland, Oregon, United States
        • Oregon Health & Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
      • Philadelphia, Pennsylvania, United States
        • Drexel University College of Medicine, Hahnemann Campus
    • Texas
      • Dallas, Texas, United States
        • University of Texas Southwestern
      • Houston, Texas, United States
        • Methodist Hospital
      • San Antonio, Texas, United States
        • University of Texas Health Sciences Center
    • Utah
      • Salt Lake City, Utah, United States
        • University of Utah
    • Vermont
      • Burlington, Vermont, United States
        • University of Vermont
    • Washington
      • Seattle, Washington, United States
        • Virginia Mason Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

To be eligible for enrollment in this study, subjects must meet the following eligibility criteria within fourteen days prior to randomization:

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Change in function as detected by the ALS Functional Rating Scale (ALSFRS-R) in patients taking minocycline compared to those taking placebo.

Secondary Outcome Measures

Outcome Measure
Changes in manual muscle testing (MMT), forced vital capacity (FVC, percent predicted), quality of life (QOL) and survival

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

  • Principal Investigator: Paul H. Gordon, M.D.,, Associate Medical Director, Eleanor and Lou Gehrig MDA/ALS Center, Columbia University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2003

Study Completion (Actual)

January 1, 2007

Study Registration Dates

First Submitted

October 16, 2002

First Submitted That Met QC Criteria

October 16, 2002

First Posted (Estimate)

October 17, 2002

Study Record Updates

Last Update Posted (Estimate)

December 21, 2007

Last Update Submitted That Met QC Criteria

December 18, 2007

Last Verified

December 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R01NS045294 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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