Effects of 5HTP and LDOPA on CNS Excitability After SCI

Study Overview
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Brief Summary
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This study will examine whether supplementation with the serotonin and dopamine precursors, 5HTP and L-DOPA can alter central nervous system excitability and improve motor function after incomplete and complete spinal cord injuries.

Official Title
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The Effects of 5-hydroxytryptophan (5-HTP) and L-3,4-dihydroxyphenylalanine (L-DOPA) Supplementation on Central Nervous System Excitability and Motor Function in Individuals With Spinal Cord Injury

Conditions
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Spinal Cord Injuries

Intervention / Treatment
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* Drug: 5HTP
* Drug: L-DOPA
* Drug: Placebo oral tablet
* Drug: Carbidopa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals aged 18-65 years of age. Patients must have suffered a trauma to the spinal cord at least 1 year ago or longer. Patients must exhibit some degree of spasticity which can be self-reported (Penn spasm frequency) or if assessed by a physiotherapist, a modified Ashworth spasticity score greater than 1 Exclusion Criteria: Individuals with damage to the nervous system other than to the spinal cord Pregnant or breastfeeding women Alcoholic patients Patients with a history of seizures or epilepsy Patients with a history of suicidal thoughts or behaviors Patients with active or inactive implants including cardiac pacemakers, implantable defibrillators, ocular implants, deep brain stimulators, vagus nerve stimulator, and implanted medication pumps Patients with conductive, ferromagnetic or other magnetic-sensitive metals implanted in their head Patients with: Known or suspected allergy to the medication or the ingredients Cardiovascular disease including history of heart attack or heart rhythm irregularities Coronary artery disease Comatose or depressed states due to CNS depressants Endocrine dysfunction Blood dyscrasias Bone marrow depression History of seizures Hypocalcemia History of stomach ulcers Wide-angle glaucoma Phenylketonuria Patients taking: Monoamine oxidase inhibitor therapy Serotonergic antidepressants: selective serotonin and norepinephrine reuptake inhibitors Tricyclic antidepressants Any type of serotonergic agonist Dopamine D2 receptor antagonists Amphetamine CNS depressants Levodopa Lithium Anti-hypertensive drugs (Carbidopa and L-DOPA) Iron salts Metoclopramide Phenothiazine medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Effects of single-dose of carbidopa (50mg) on CNS excitability<br>Participants will visit the lab and on one of four different occasions they will receive carbidopa only (50 mg). Neurophysiology outcome measures will be obtained at 30, 60, 90, 120 and 150 min post drug-intake. | Drug: Carbidopa<br>* Carbidopa (50mg)<br>|
| Placebo Comparator: Effects of single-dose placebo on CNS Excitability<br>Participants will visit the lab and on one of four different occasions and will receive a placebo. Neurophysiology outcome measures will be obtained at 30, 60, 90, 120 and 150 min post drug-intake. | Drug: Placebo oral tablet<br>* Placebo<br>|
| Active Comparator: Effects of single-dose 5HTP/carbidopa on CNS Excitability<br>During one of the four occasions participants visit the lab they will receive 5HTP combined with carbidopa (50-200mg HTP/50mg carbidopa). Neurophysiology outcome measures will be obtained at 30, 60, 90, 120 and 150 min post drug-intake. | Drug: 5HTP<br>* 5HTP/carbidopa (50-200 mg 5-HTP/50 mg carbidopa)<br>* Other names: carbidopa;|
| Active Comparator: Effects of single-dose L-DOPA/carbidopa on CNS Excitability<br>During one of the four occasions participants visit the lab they will receive L-DOPA combined with carbidopa (50-200mg L-DOPA/50mg carbidopa). Neurophysiology outcome measures will be obtained at 30, 60, 90, 120 and 150 min post drug-intake. | Drug: L-DOPA<br>* L-DOPA/carbidopa (50-200 mg L-DOPA/50 mg carbidopa)<br>* Other names: Carbidopa;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in corticospinal excitability | Transcranial magnetic stimulation motor-evoked potentials | Pre drug-intake, 30minutes, 60minutes, 90minutes, 120minutes post drug-intake | 
| Change in motoneuron excitability | F waves | Pre drug-intake, 30minutes, 60minutes, 90minutes, 120minutes post drug-intake | 
| Change in spinal excitability | H reflex | Pre drug-intake, 30minutes, 60minutes, 90minutes, 120minutes post drug-intake | 
| Change in spasticity | Cutaneomuscular reflex | Pre drug-intake, 30minutes, 60minutes, 90minutes, 120minutes post drug-intake | 
| Change in movement performance | Leg cycling | Pre drug-intake, 120-150minutes post drug-intake | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Analysis 5-HIAA | 5-HIAA (serum) | 90-120minutes post drug-intake | 
| Serum Analysis 5-HT | 5-HT (serum) | 90-120minutes post drug-intake | 
| Whole blood analysis 5-HT | 5-HT (whole blood) | 90-120minutes post drug-intake | 
| Serum analysis Cortisol | Cortisol level | 90-120minutes post drug-intake | 
| Serum and Urine Analysis of dopamine | catecholamines and homovanillic acid (urine) | 90-120min post drug-intake | 
| Serum Catechloamines | catecholamines and homovanillic acid (urine) | 90-120minutes post drug-intake | 
| Urine Homovanillic acid | homovanillic acid (urine) | 90-120minutes post drug-intake |