Efficacy and Safety of 4-aminopyridine on Cognitive Performance and Motor Function of Patients With Multiple Sclerosis
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Intervention: 4-aminopyridine; Placebo
Intervention description: 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.; The placebo arm will include Microcrystalline Cellulose placebo
Intervention MeSH terms: 4-Aminopyridine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Cognitive function; Multiple sclerosis; 4-aminopyridine; Fatigue

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.
    

Eligibility criteria:

        Inclusion Criteria: Patients with multiple sclerosis (MS) are eligible for the study if
        they meet the following criteria:

          1. Relapsing recurrent MS with an evolution of at last 6 months before the study began.

          2. Both males and females, aged 20 - 65 years

          3. Neurologic Expanded Disability Status Scale (EDSS) 3 - 7

          4. Who are in first-line immunomodulatory therapy and have a stable disease

          5. No more than one outbreak per year.

          6. The absence of antiepileptic antecedent and electroencephalogram without epileptic
             activity.

          7. For females: postmenopausal or surgically sterile, or using an acceptable method of
             birth control

        Exclusion Criteria:

          1. History of cardiovascular disease (syncope, arrhythmia, or myocardial infarction
             within the last two years), systolic blood pressure greater than 150 or less than 70
             mm Hg, diastolic blood pressure greater than 110 or less than 50 mm Hg, or heart rate
             greater than 110 or less than 50 beats/minute; impaired hepatic function (total
             hepatic enzyme or bilirubin levels greater than 2 times the upper limits of normal) or
             impaired renal function (creatinine level greater than 2 times the upper limits of
             normal) less than 6 months before the study

          2. Known allergy to pyridine-containing drugs

          3. Neurologic, degenerative, or psychiatric disorders that would impair the patient's
             ability to complete the protocol

          4. Any illness or abnormality that would jeopardize patient safety or interfere with the
             conduct of the study

          5. History of substance abuse

          6. Inability to discontinue excluded concomitant drug therapy