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

NCT ID: NCT03899584

Last Updated: 2021-02-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-17
• Study Completion Date: 2023-12-31

Brief Summary

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.

Detailed 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.

Conditions

Spinal Cord Injuries; Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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).

Group Type: ACTIVE_COMPARATOR

4-Aminopyridine

Intervention Type: DRUG

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.

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.

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type: DRUG

The placebo arm will include a placebo of microcrystalline cellulose.

Interventions

4-Aminopyridine

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.

Intervention Type: DRUG

Placebo oral capsule

The placebo arm will include a placebo of microcrystalline cellulose.

Intervention Type: DRUG

Other Intervention Names

4-AP; Microcrystalline cellulose

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Coordinación de Investigación en Salud, Mexico

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martín Paredes Cruz, MSc

Role: PRINCIPAL_INVESTIGATOR

Instituto Mexicano del Seguro Social

Israel Grijalva Otero, PhD

Role: STUDY_DIRECTOR

Instituto Mexicano del Seguro Social

Locations

Hospital de Especialidades, CMN Siglo XXI

Mexico City, , Mexico

Countries

Mexico

References

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Other Identifiers

2010-785-073

Identifier Type: -

Identifier Source: org_study_id