High Doses of 4-aminopyridine in Clinically Complete Chronic Spinal Cord Injury Patients.
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|ClinicalTrials.gov Identifier: NCT03899584|
Recruitment Status : Not yet recruiting
First Posted : April 2, 2019
Last Update Posted : May 30, 2019
|Condition or disease||Intervention/treatment||Phase|
|Spinal Cord Injuries Chronic||Drug: 4-Aminopyridine Drug: Placebo oral capsule||Phase 3|
Consecutive patients with chronic AIS A tetraplegic or paraplegic with an MRI showing cord continuity will be recruited in the departments of neurology, neurosurgery or rehabilitation from hospitals of Social Security Mexican Institute (IMSS) in 8 states . Just patients who meeting inclusion criteria, will be selected for the study until reach 150. After signing an informed consent, they will be randomized into 75 for the intervention arm and 75 for the placebo arm. All patients will receive capsules for daily consumption according to their assignment. They will receive ascending doses of the drug starting with 10 milligrams and progressively increasing every 2 to 4 weeks 10 mg until reaching the maximum dose proposed according to weight (maximum 1 mg/kg/d). Questionnaires and functional evaluations will be administered at the beginning of the study, and at the end of the treatment to evaluate the efficacy. The evaluations include the International Standards for Neurological Classification of Spinal Cord Injury motor and sensory Scale, the Spinal Cord Injury Independence Measure (SCIM III), quality of life (SF-36), sphincter bladder/anal sensation/control in both genders and psychogenic erection in males as primary outcomes.
After the follow-up period, all test results will be analyzed and compared to determine the efficacy and safety of 4-aminopyridine. The Mann-Whitney U and Chi-square test will be used for statistical analysis.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||150 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Quality of Life, Efficacy and Safety of High Doses of 4-aminopyridine in Patients With Clinically Complete Chronic Spinal Cord Injury: Multicenter, Randomized, Double Blind, Placebo Controlled Clinical Trial|
|Estimated Study Start Date :||July 2019|
|Estimated Primary Completion Date :||May 2021|
|Estimated Study Completion Date :||May 2021|
Active Comparator: Treatment with 4-aminopyridine
The 4-aminopyridine will be administered in the form of gelatin capsules containing 4-aminopyridine 10 mg and microcrystalline cellulose as excipient. The dose of 4-aminopyridine will increase 10 mg / every 2 to 4 weeks until reaching the maximum dose proposed by weight ( maximum 1 mg / kg / d).
Each patient will take 10 mg per kilogram of weight (example: a person weighing 60 kg, will take two capsules three times a day after meals, for a total of 6 capsules / day). Each capsule will contain 10 milligrams of 4-Aminopyridine that will allow to be administered sequentially at progressively higher doses / day. The dose of 4-aminopyridine will increase 10 mg / 2 to 4 weeks.
Other Name: 4-AP
Placebo Comparator: Placebo oral capsule
Patients randomized to the placebo sequence will receive placebo in the same way as those who will take 4-AP. They will be blinded to the fact that they are taking placebo and the capsules will be identical in appearance to the intervention capsules.
Drug: Placebo oral capsule
The placebo arm will include a placebo of microcrystalline cellulose.
Other Name: Microcrystalline cellulose
- Changes in Sensory Function [ Time Frame: From baseline at 6 months after treatment ]This function will be examined using the ASIA International Standards for the Neurological and Functional Classification of Spinal Cord Injury. Sensory function will be evaluated and qualify for two modes, pin prick / light touch in all dermatomes. The first one will be measured with the sharp and blunt end of a safety pin and the last one will be evaluated with a cotton ball. A scale of 3 points (0- 2) will be used depending on whether the modality is normal (2), diminished (1) or absent (0). A score of 2 for each of the 28 key sensory points tested on each side of the body would result in a maximum score of 56 for pin prick, 56 for light touch, and a total of 112, higher values represent a better outcome.
- Changes in Motor function [ Time Frame: From baseline at 6 months after treatment ]Motor function will be examined using the ASIA International Standards for the Neurological and Functional Classification of Spinal Cord Injury. Muscle strength will be evaluated in each of the 20 key muscles, five in each limb, representing segments of the spinal cord C5 through T1 and L2 through S1, using a six-point rating scale (0-5). There is a maximum score of 25 for each extremity, totaling 50 for the upper limbs and 50 for the lower limbs. Changes in motor score (total range from 0 to 100, higher values represent a better outcome).
- Changes in the functional assement of Spinal Cord Independence [ Time Frame: From baseline at 6 months after treatment ]The Spinal Cord Independence Measure version III (SCIM III) has 16 questions on self-care, respiratory and sphincter management and mobility in and out of home, which ranges from 0 (total dependence) to 100 points (total Independence).
- Changes in the Sphincters function [ Time Frame: From baseline at 6 months after treatment ]The function of the anal sphincter and the bladder will be evaluated. The anal function will be qualified as a sensation when the patient can differentiate when the rectum is full and ready to empty and control when the patient can stop the fecal evacuation with enough time to reach the bathroom and eliminate the fecal material. The function of the bladder will be classified in the same way as the anal function. Positive or negative will be the final result of sensation and control.
- Change of overall quality of life score as measured by Short Form-36 (SF-36) [ Time Frame: From baseline at 6 months after treatment ]The Short Form-36 (SF-36) has 36 questions. Each question has a score, which will be transformed into a 0 to 100 scale, where 0 corresponds to "the worst health state" and 100 to "the best health state".
- Changes in Mean International Index of Erectile Function [ Time Frame: From baseline at 6 months after treatment ]The international Index of Erectile Function (IIEF) contains 15 questions, rated from 0 or 1 to 5, yielding an overall score of 5-75 points. A score of 1-10 indicates severe erectile dysfunction, 11-16 moderate dysfunction, 17-25 mild dysfunction, and greater than 25 "normal" function.
- Incidence of Treatment-Emergent Adverse Events (Safety) [ Time Frame: 6 months ]Safety will be measured by occurrence of Treatment-Emergent Adverse Events (TRAEs); data will represent the number of participants with abnormal laboratory values and/or adverse events that are related to treatment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03899584
|Contact: Israel Grijalva Otero, PhDfirstname.lastname@example.org|
|Contact: Susana Navarrete Navarro, PhD||+52-55-56276900 ext email@example.com|
|Principal Investigator:||Martín Paredes Cruz, MSc||Instituto Mexicano del Seguro Social|
|Study Director:||Israel Grijalva Otero, PhD||Instituto Mexicano del Seguro Social|