Minocycline to Treat Amyotrophic Lateral Sclerosis
Information source: National Institute of Neurological Disorders and Stroke (NINDS)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Amyotrophic Lateral Sclerosis
Intervention: minocycline (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: National Institute of Neurological Disorders and Stroke (NINDS) Official(s) and/or principal investigator(s):
Paul H. Gordon, M.D.,, Principal Investigator, Affiliation: Associate Medical Director, Eleanor and Lou Gehrig MDA/ALS Center, Columbia University Medical Center
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).
Clinical Details
Study design: Treatment, Randomized, Double-Blind, Placebo Control
Primary outcome: Change in function as detected by the ALS Functional Rating Scale (ALSFRS-R) in patients taking minocycline compared to those taking placebo.
Secondary outcome: Changes in manual muscle testing (MMT), forced vital capacity (FVC, percent predicted), quality of life (QOL) and survival
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.
Eligibility
Minimum age: 21 Years.
Maximum age: 85 Years.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
Mayo Clinic, Scottsdale, Arizona, United States
California Pacific Medical Center, San Francisco, California, United States
University of California Department of Neurology, Los Angeles, California, United States
University of California, Irvine, Irvine, California, United States
Univ. of Colorado Health Sciences Center, Denver, Colorado, United States
Mayo Clinic, Jacksonville, Florida, United States
University of Illinois, Chicago, Illinois, United States
Indiana University School of Medicine, Indianapolis, Indiana, United States
University of Iowa, Iowa City, Iowa, United States
University of Kansas Medical Center, Kansas City, Kansas, United States
University of Kentucky, Lexington, Kentucky, United States
University of Minnesota, Minneapolis, Minnesota, United States
Hennepin County Med Center, Minneapolis, Minnesota, United States
Washington University, St. Louis, Missouri, United States
UMDNJ/Robert Wood Johnson Medical Center, New Brunswick, New Jersey, United States
University of New Mexico, Albuquerque, New Mexico, United States
Columbia Unversity, Eleanor and Lou Gehrig MDA/ALS Center, New York, New York 10032, United States
Carolinas Medical Center, Charlotte, North Carolina, United States
Wake Forest University, Winston- Salem, North Carolina, United States
Duke University, Durham, North Carolina, United States
Metro Health Clinic, Cleveland, Ohio, United States
Oregon Health & Science University, Portland, Oregon, United States
Drexel University College of Medicine, Hahnemann Campus, Philadelphia, Pennsylvania, United States
University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
University of Texas Health Sciences Center, San Antonio, Texas, United States
Methodist Hospital, Houston, Texas, United States
University of Texas Southwestern, Dallas, Texas, United States
University of Utah, Salt Lake City, Utah, United States
University of Vermont, Burlington, Vermont, United States
Virginia Mason Medical Center, Seattle, Washington, United States
Additional Information
Starting date: January 2003
Ending date: January 2007
Last updated: December 18, 2007
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