Spinal cord injury Injury, Occupational Diseases, Poisoning Other injuries of spine and trunk, level unspecified
Conditions
Interventions
First phase: Randomised double-blind placebo-controlled trial. Identical capsules containing 4-AP (oral) 5 mg or placebo were prepared. The 4-AP as given as gelatin capsules containing 4-AP 5 mg and m
Sponsors
Mexican Social Security Institute (Instituto Mexicano del Seguro Social) (Mexico)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients with SCI were eligible for the study if they met the following criteria: 1. Tetraplegia or paraplegia for more than 1.5 years before the study began, 2. Both males and females, aged 18-60 years 3. Neurologic injury level of C4-L1 4. Medically stable and able to breathe independently 5. Stable neurologic deficits for more than 90 days before the study 6. Absence of antiepileptic antecedent and electroencephalogram without epileptic activity, and paralysed extremities without passive limitations (healthy joints) 7. For females: postmenopausal or surgically sterile, or using an acceptable method of birth control
Exclusion criteria
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. Known 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 patients safety or interfere with the conduct of the study 6. History of substance abuse 7. Inability to discontinue excluded concomitant drug therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Motor and sensation measurements: Sensory function was tested and scored for 2 modalities: pin prick and light touch in all dermatomes. Muscle strength was tested in each of the 20 key muscles. Evaluation of both sides was expressed in a single score. The American Spinal Cord Injury Association (ASIA) Impaired Scale (AIS) was used to classify the cases as complete or incomplete. 2. Independence measurements: The Spinal Cord Injury Independence Measure 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). Timepoints of assessment for all primary and secondary outcome measures: Patients in the double-blind controlled trial were subjected to pretreatment assessment and at 12 and 24 weeks after starting the 4-AP. Patients in the open-label trial were evaluated at month 6 and 12 of continued treatment or at time when the highest doses of 4-AP were reached before the end of the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Somatosensory evoked potentials (SSEPs), sphincter bladder/anal sensation/control in both genders, psychogenic erection in males: 2. Sphincter function: The anal function was graded as sensation when the patient was able to differentiate when the rectum was full and ready to empty, and control when the patient was able to stop the faecal evacuation with enough time to get the bathroom and eliminate the faecal material. Bladder function was graded as was done for anal function. Positive or negative was the final result of both sensation and control. 3. Psychogenic erection was evaluated in male patients. Presence or absence was the final result. 4. Electrophysiological evaluation: The SSEPs were elicited by electrical stimulation 5. Safety evaluation: Safety surveillance was done every 4 weeks from the beginning of the study, intentionally searching for AR, measuring vital signs, doing physical examinations and performing EEG and laboratory tests (blood and urine samples: creatinine, blood urea nitrogen, total cholesterol, tryglycerides, total direct, and indirect bilirubin, alanine aminotransferase, aspartate aminotrasferase, alkaline phosphatase, creatinine kinase, lactic acid dehydrogenase, sodium, potassium, chloride, calcium and phosphorus. A complete blood cell count with differentials and a routine urialysis and urine culture also obtained at each visit) Timepoints of assessment for all primary and secondary outcome measures: Patients in the double-blind controlled trial were subjected to pretreatment assessment and at 12 and 24 weeks after starting the 4-AP. Patients in the open-label trial were evaluated at month 6 and 12 of continued treatment or at time when the highest doses of 4-AP were reached before the end of the study. | — |
Countries
Mexico
Outcome results
None listed