Spinal Cord Injuries Clinical Trial
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
Verified date | February 2021 |
Source | Coordinación de Investigación en Salud, Mexico |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Active, not recruiting |
Enrollment | 150 |
Est. completion date | December 2023 |
Est. primary completion date | December 2022 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 60 Years |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
Mexico | Hospital de Especialidades, CMN Siglo XXI | Mexico City |
Lead Sponsor | Collaborator |
---|---|
Coordinación de Investigación en Salud, Mexico |
Mexico,
Cardenas DD, Ditunno J, Graziani V, Jackson AB, Lammertse D, Potter P, Sipski M, Cohen R, Blight AR. Phase 2 trial of sustained-release fampridine in chronic spinal cord injury. Spinal Cord. 2007 Feb;45(2):158-68. Epub 2006 Jun 13. — View Citation
Cardenas DD, Ditunno JF, Graziani V, McLain AB, Lammertse DP, Potter PJ, Alexander MS, Cohen R, Blight AR. Two phase 3, multicenter, randomized, placebo-controlled clinical trials of fampridine-SR for treatment of spasticity in chronic spinal cord injury. Spinal Cord. 2014 Jan;52(1):70-6. doi: 10.1038/sc.2013.137. Epub 2013 Nov 12. — View Citation
DeForge D, Nymark J, Lemaire E, Gardner S, Hunt M, Martel L, Curran D, Barbeau H. Effect of 4-aminopyridine on gait in ambulatory spinal cord injuries: a double-blind, placebo-controlled, crossover trial. Spinal Cord. 2004 Dec;42(12):674-85. — View Citation
Donovan WH, Halter JA, Graves DE, Blight AR, Calvillo O, McCann MT, Sherwood AM, Castillo T, Parsons KC, Strayer JR. Intravenous infusion of 4-AP in chronic spinal cord injured subjects. Spinal Cord. 2000 Jan;38(1):7-15. — View Citation
Grijalva I, García-Pérez A, Díaz J, Aguilar S, Mino D, Santiago-Rodríguez E, Guizar-Sahagún G, Castañeda-Hernández G, Maldonado-Julián H, Madrazo I. High doses of 4-aminopyridine improve functionality in chronic complete spinal cord injury patients with MRI evidence of cord continuity. Arch Med Res. 2010 Oct;41(7):567-75. doi: 10.1016/j.arcmed.2010.10.001. — View Citation
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Potter PJ, Hayes KC, Hsieh JT, Delaney GA, Segal JL. Sustained improvements in neurological function in spinal cord injured patients treated with oral 4-aminopyridine: three cases. Spinal Cord. 1998 Mar;36(3):147-55. — View Citation
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* Note: There are 16 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Changes in Sensory Function | 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. | From baseline at 6 months after treatment | |
Primary | Changes in Motor function | 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). | From baseline at 6 months after treatment | |
Primary | Changes in the functional assement of Spinal Cord Independence | 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). | From baseline at 6 months after treatment | |
Primary | Changes in the Sphincters function | 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. | From baseline at 6 months after treatment | |
Primary | Change of overall quality of life score as measured by Short Form-36 (SF-36) | 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". | From baseline at 6 months after treatment | |
Primary | Changes in Mean International Index of Erectile Function | 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. | From baseline at 6 months after treatment | |
Primary | Incidence of Treatment-Emergent Adverse Events (Safety) | 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. | 6 months |
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