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	Treatment or Intervention	Phase
Amyotrophic Lateral Sclerosis	Drug: minocycline	Phase III

Further Study Details: 

 

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 shown to slow ALS deterioration in animal studies.

The 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.

 

Ages Eligible for Study:  21 Years   -   85 Years,  Genders Eligible for Study:  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 2.0).
• 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 1:80 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.

 

Nayra Gad      212-305-3985    NG152@columbia.edu
 

Arizona
      Mayo Clinic, Scottsdale,  Arizona,  United States; Recruiting

California
      California Pacific Medical Center, San Francisco,  California,  United States; Recruiting

      University of California, Los Angeles,  California,  United States; Recruiting

      University of California, San Francisco,  California,  United States; Recruiting

Colorado
      Univ. of Colorado Health Sciences Center, Denver,  Colorado,  United States; Recruiting

District of Columbia
      George Washington University, Washington,  District of Columbia,  United States; Recruiting

Indiana
      Indiana University, Indianapolis,  Indiana,  United States; Recruiting

Kansas
      University of Kansas Medical Center, Kansas City,  Kansas,  United States; Recruiting

Kentucky
      University of Kentucky, Lexington,  Kentucky,  United States; Recruiting

Massachusetts
      Massachusetts General Hospital, Boston,  Massachusetts,  United States; Recruiting

Minnesota
      University of Minnesota, Minneapolis,  Minnesota,  United States; Recruiting

      Hennepin County Med Center, Minneapolis,  Minnesota,  United States; Recruiting

Missouri
      Washington University, St. Louis,  Missouri,  United States; Recruiting

New Mexico
      University of New Mexico, Albuquerque,  New Mexico,  United States; Recruiting

New York
      Columbia-Presbyterian Medical Center Neurological Institute, New York,  New York,  10032,  United States; Recruiting

      State University of New York Upstate Med Center, Syracuse,  New York,  United States; Recruiting

North Carolina
      Carolinas Medical Center, Charlotte,  North Carolina,  United States; Recruiting

      Wake Forest University, Winston Salem,  North Carolina,  United States; Recruiting

Oregon
      University of Oregon, Portland,  Oregon,  United States; Recruiting

Pennsylvania
      Drexel University College of Medicine, Philadelphia,  Pennsylvania,  United States; Recruiting

Texas
      University of Texas Health Sciences Center, San Antonio,  Texas,  United States; Recruiting

      Baylor College of Medicine, Houston,  Texas,  United States; Recruiting

Utah
      University of Utah, Salt Lake City,  Utah,  United States; Recruiting

Washington
      Virginia Mason Medical Center, Seattle,  Washington,  United States; Recruiting

Study chairs or principal investigators

Paul H. Gordon, M.D.,,  Principal Investigator,  Columbia-Presbyterian Medical Center Neurological Institute   

Study ID Numbers  R01NS45294
Study Start Date January 2003
Record last reviewed  October 2003
NLM Identifier  NCT00047723
ClinicalTrials.gov processed this record on 2003-11-21