Minocycline to Treat Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00047723
• Other study ID #: R01NS045294
• Status: Completed
• Phase: Phase 3
• First received: October 16, 2002
• Last updated: December 18, 2007
• Start date: January 2003
• Est. completion date: January 2007

Study information

• Verified date: December 2007
• Source: National Institute of Neurological Disorders and Stroke (NINDS)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 400
• Est. completion date: January 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 85 Years

Eligibility

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 Design

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• minocycline

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 Grou — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in function as detected by the ALS Functional Rating Scale (ALSFRS-R) in patients taking minocycline compared to those taking placebo.
Secondary	Changes in manual muscle testing (MMT), forced vital capacity (FVC, percent predicted), quality of life (QOL) and survival