Overview

This trial is active, not recruiting.

Condition multiple sclerosis
Treatments 4-aminopyridine, placebo
Phase phase 2
Sponsor Coordinación de Investigación en Salud, Mexico
Start date October 2014
End date February 2016
Trial size 24 participants
Trial identifier NCT02280096, 2012-785-091

Summary

Twenty four 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-AP for a period of four months in increasing doses.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Active Comparator)
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 6 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. After 22 weeks of treatment and 2 weeks of wash-out period, this group of patients will start placebo branch.
4-aminopyridine It does not apply.
Each patient will take two capsules every 6 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. After 22 weeks of treatment and 2 weeks of wash-out period, this group of patients will start placebo branch.
(Placebo Comparator)
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. Then, after a 2 weeks wash-out period, they will receive 4-aminopyridine in the same way as it was described previously.
placebo Does not apply
The placebo arm will include Microcrystalline Cellulose placebo

Primary Outcomes

Measure
The Brief Repeatable Battery of Rao
time frame: 9 months
Integrated Program of Neuropsychological Exploration Test Barcelona
time frame: 9 months
Rey-Osterrieth Complex Figure Test (ROCF)
time frame: 9 months
Tower Of London (TOL)
time frame: 9 months
Five Digit Test (FDT)
time frame: 9 months
Wisconsin Card Sorting Test (WCST)
time frame: 9 months
Color Trails Test (CTT)
time frame: 9 months

Secondary Outcomes

Measure
Improved physical capacity
time frame: 9 months
Fatigue
time frame: 9 months
Walk
time frame: 9 months
Spasticity
time frame: 9 months
Safety evaluation
time frame: 9 months

Eligibility Criteria

Male or female participants from 18 years up to 60 years old.

Inclusion Criteria: Patients with ME are eligible for the study if they meet the following criteria: 1. Relapsing recurrent MEwith an evolution of at last 6 months before the study began. 2. Both males and females, aged 20 - 65 years 3. Neurologic 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. 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

Additional Information

Official title Efficacy and Safety of 4-aminopyridine on Cognitive Performance and Motor Function of Patients With Multiple Sclerosis. Randomized, Blinded, Placebo-controlled Clinical Trial.
Principal investigator Claudia Arreola Mora, MS
Description Consecutive patients with stable multiple sclerosis are being recruited from the neurological services of IMSS at the hospital CMN Siglo XXI 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 4 months. A battery of neuropsychological tests will be administered at baseline, after 4 months, and after an additional four months 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 aforementioned 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.
Trial information was received from ClinicalTrials.gov and was last updated in December 2015.
Information provided to ClinicalTrials.gov by Coordinación de Investigación en Salud, Mexico.