Clinical trial NCT02280096
Conditions: Multiple Sclerosis
Keywords: Cognitive function Multiple sclerosis 4-aminopyridine Fatigue
Sponsor: Coordinación de Investigación en Salud, Mexico
Start date: 2014-10-01; Completion date: 2017-02-01
Enrollment: 24 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Twenty four relapsing-remitting multiple sclerosis (RRMS) patients over the age of 18, with similar degree of disability, and with an evolution of at last 6 months, who are in first-line immunomodulatory therapy and have a stable disease (no more than one outbreak per year) will be included in the present study. Patients will be administered a neuropsychological test battery selected for this study and divided into two sessions of one and a half-hour each. Emotional state will be assessed with the Beck Depression Inventory in a different session. Cognitive impairment is defined as the alteration of two or more neuropsychological tests. Patients will be divided randomly into two groups where one will receive placebo and the other one 4-Aminopyridine (4-AP) for a period of 22 weeks in increasing doses.

Detailed description:
Consecutive patients with stable multiple sclerosis are being recruited from the neurological services of Social Security Mexican Institute (IMSS) at the National Medical Center (CMN) "Siglo XXI" Specialties Hospital over the period of 1 year. Of those meeting inclusion criteria, 24 will be selected for the study. After signing an informed consent, they will be randomized into 12 for the intervention arm and 12 for the placebo arm. All patients will receive capsules for daily consumption according to their assignment, with no visible difference between capsules. Dosage will be 6.5-7.5 mg/kg to a limit of 50 mg. These capsules will be taken for a period of 22 weeks. A battery of neuropsychological tests will be administered at baseline, after 22 weeks, and after an additional 22 weeks of follow-up to assess cognitive performance and motor function. Emotional state will be assessed with the Beck Depression Inventory at each of the three afore mentioned points.

After the follow-up period, all test results will be analyzed and compared to determine the efficacy and safety of 4-aminopyridine on the cognitive performance and motor function of patients. Mann-Whitney U will be used for statistical analysis.

Arms: arm 1: 4-aminopyridine is given as gelatin capsules containing 4-aminopyridine 10 mg and microcrystalline cellulose as the excipient. Each patient will take two capsules every 8 hours after meals, for a total of 6 capsules/day. The 4-aminopyridine dosage will increase 10 mg/4 weeks by substitution of placebo instead of 4-aminopyridine capsules; such that patients will receive from 40 to 60 mg. distribute in 6capsules/day throughout the study. arm 2: Patients randomized to the placebo sequence will receive placebo for 20 weeks after the run-in period. They will be blinded to the fact that they are taking placebo, and capsules will be identical in appearance to the intervention capsules.
Interventions: intervention 1: 4-aminopyridine intervention 2: Placebo
Intervention descriptions: intervention 1: Each patient will take two capsules every 8 hours after meals, for a total of 6 capsules/day. The 4-aminopyridine dosage will increase 10 mg/4 weeks by substitution of placebo instead of 4-aminopyridine capsules; such that patients will receive from 40 to 60 mg. distribute in 6capsules/day throughout the study. intervention 2: The placebo arm will include Microcrystalline Cellulose placebo

Protocol documents: