Minocycline to Treat Amyotrophic Lateral Sclerosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00047723
Recruitment Status : Completed
First Posted : October 17, 2002
Last Update Posted : December 21, 2007
Information provided by:
National Institute of Neurological Disorders and Stroke (NINDS)

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: minocycline Phase 3

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  (Clinical Trial)
Enrollment : 400 participants
Allocation: Randomized
Masking: Double
Primary Purpose: Treatment
Study Start Date : January 2003
Actual Study Completion Date : January 2007

Primary Outcome Measures :
  1. 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 :
  1. Changes in manual muscle testing (MMT), forced vital capacity (FVC, percent predicted), quality of life (QOL) and survival

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   21 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00047723

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

Publications of Results: Identifier: NCT00047723     History of Changes
Other Study ID Numbers: R01NS045294 ( U.S. NIH Grant/Contract )
First Posted: October 17, 2002    Key Record Dates
Last Update Posted: December 21, 2007
Last Verified: December 2007

Keywords provided by National Institute of Neurological Disorders and Stroke (NINDS):
amyotrophic lateral sclerosis

Additional relevant MeSH terms:
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Anti-Bacterial Agents
Anti-Infective Agents