Effects of 5HTP and LDOPA on CNS Excitability After SCI

Phase 2

Suspended

• Conditions: Spinal Cord Injuries
• Interventions: Drug: 5HTP; Drug: Placebo oral tablet; Drug: Carbidopa; Drug: L-DOPA

• Registration Number: NCT04000919
• Lead Sponsor: Jessica M D'Amico

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-06-19
• Study First Submitted: 2019-06-19
• Study First Submitted QC: 2019-06-25
• Study First Posted: 2019-06-27
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-13
• Last Update Posted: 2022-10-17
• Primary Completion: 2023-06-30
• Study Completion: 2023-12-30

Recruitment & Eligibility

• Status: SUSPENDED
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Effects of single-dose 5HTP/carbidopa on CNS Excitability	5HTP	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.
Effects of single-dose placebo on CNS Excitability	Placebo oral tablet	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.
Effects of single-dose of carbidopa (50mg) on CNS excitability	Carbidopa	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.
Effects of single-dose L-DOPA/carbidopa on CNS Excitability	L-DOPA	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Louisville, Kentucky Spinal Cord Injury Research Centre; 🇺🇸 Louisville, Kentucky, United States