Minocycline to Treat Amyotrophic Lateral Sclerosis

• ClinicalTrials.gov Identifier: NCT00047723
• Recruitment Status: Completed
• First Posted: October 17, 2002
• Last Update Posted: December 21, 2007
• Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by: National Institute of Neurological Disorders and Stroke (NINDS)

Tracking Information

• First Submitted Date: October 16, 2002
• First Posted Date: October 17, 2002
• Last Update Posted Date: December 21, 2007
• Study Start Date: January 2003
• Primary Completion Date: Not Provided
• Current Primary Outcome Measures (submitted: January 10, 2006): Change in function as detected by the ALS Functional Rating Scale (ALSFRS-R) in patients taking minocycline compared to those taking placebo.
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures (submitted: January 10, 2006): Changes in manual muscle testing (MMT), forced vital capacity (FVC, percent predicted), quality of life (QOL) and survival
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Minocycline to Treat Amyotrophic Lateral Sclerosis
• Official Title: Not Provided
• 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).

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
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Masking: Double; Primary Purpose: Treatment
• Condition: Amyotrophic Lateral Sclerosis
• Intervention: Drug: minocycline
• Study Arms: Not Provided
• Publications *: 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 Group. Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial. Lancet Neurol. 2007 Dec;6(12):1045-53. doi: 10.1016/S1474-4422(07)70270-3. Epub 2007 Nov 5.

Recruitment Information

• Recruitment Status: Completed
• Enrollment (submitted: June 23, 2005): 400
• Original Enrollment: Same as current
• Actual Study Completion Date: January 2007
• Primary Completion Date: Not Provided

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00047723
• Other Study ID Numbers: R01NS045294( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Not Provided
• Original Responsible Party: Same as current
• Current Study Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: National Institute of Neurological Disorders and Stroke (NINDS)
• Verification Date: December 2007