High Doses of 4-aminopyridine in Clinically Complete Chronic Spinal Cord Injury Patients.

Coordinación de Investigación en Salud, Mexico

Status and phase: Unknown; Phase 3

Conditions: Chronic; Spinal Cord Injuries

Treatments: Drug: Placebo oral capsule; Drug: 4-Aminopyridine

Study type: Interventional

Funder types: Other

Identifiers

NCT03899584

2010-785-073

Details and patient eligibility

About

150 patients with clinically complete chronic spinal cord Injury will be included in a randomized, parallel, placebo controlled, multi-centric, phase III trial. Patients will be evaluated before starting the medication, and at the end of the treatment in the locomotor, sensory, grade of independence, sensitivity and control of bladder and anal sphincters, quality of life, and psychogenic erection in males. Patients will be divided randomly into two groups where one will receive placebo and the other one 4-Aminopyridine (4-AP) in a maximum of 30 weeks in increasing doses.

Full description

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.

Enrollment: 150 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria: Patients with spinal cord injury (SCI) will be eligible for the study if they meet the following criteria:

1. Chronic AIS A tetraplegia or paraplegia for more tan 2 years before the study begin.
2. MRI showing cord continuity.
3. Neurologic Injury level of C4-T12.
4. Medically stable and able to breathe independently.
5. Stable neurologic deficits for more than 60 days before the study.
6. The absence of antiepileptic antecedent and electroencephalogram without epileptic activity.
7. They have maintained some type of rehabilitation after injury in the affected limbs and paralyzed extremities without passive limitations (healthy joints)
8. For females: postmenopausal or surgically sterile, or using an acceptable method of birth control.

Exclusion Criteria:

1. Pressure ulcers, skin infections, or phlebitis
2. 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
3. Know allergy to pyridine-containing drugs
4. Neurologic, degenerative, or psychiatric disorders that would impair the patient's ability to complete the protocol
5. Any illness or abnormality that would jeopardize patient safety or interfere with the conduct of the study
6. Inability to discontinue excluded concomitant drug therapy
7. Were pregnant or lactating
8. Had received any other investigational drug less tan 30 days before the study
9. History of drug or alcohol abuse
10. Treatment with and anti-spasticity compound and could not maintain a stable daily dosage
11. Had received any drug known to cause significant major organ toxicity less tan 3 months before the study
12. Peripheral neuropathy
13. Treatment with corticosteroids

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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150 participants in 2 patient groups, including a placebo group

Treatment with 4-aminopyridine

Active Comparator group

Description:

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).

Treatment:

Drug: 4-Aminopyridine

Placebo oral capsule

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo oral capsule