Effects of 5HTP on the Injured Human Spinal Cord (5-HTP only)

Effects of the Serotonin Precursor, 5-hydroxytryptophan, in the Injured Human Spinal Cord

This study will assess how the serotonin precursor, 5-HTP, alter nervous system excitability and motor function in individuals with spinal cord injuries of differing chronicity and severity. Participants will visit the lab on 4 separate occasions where they will be administered four different drugs in a randomized, double-blinded, placebo-controlled crossover design.

Study Overview

• Status: Recruiting
• Conditions: Spinal Cord Injuries
• Intervention / Treatment: Drug: Placebo; Drug: 5-Hydroxytryptophan; Drug: Carbidopa; Drug: 5-Hydroxytryptophan 100 MG

Detailed Description

This study will assess for the first time the effects of 5-HTP on neural excitability utilizing a combination of neurophysiological and functional testing in subacute motor complete (AIS A/B), chronic motor complete (AIS A/B) and chronic incomplete (AIS C/D) SCI participants. To reduce peripheral side effects such as nausea, these supplements will be co-administered with carbidopa which inhibits the action of peripheral AADC, thereby ensuring that 5-HTP can effectively cross the blood brain barrier prior to being broken down. The neurophysiological outcomes will allow for the determination of the mechanistic actions of each pharmacological agent on different pathways/sites within the central nervous system in three different patient populations with varying degrees of lesion severity and will for the determination of whether increased Amino Acid Decarboxylase (AADC) expression and therefore the efficacy of this approach is correlated to lesion severity and/or chronicity. Importantly, the use of functional testing will allow for the determination of whether these often-reported neurophysiological changes translate to improvements in muscle activation patterns and kinematics during cycling.

The effects of 5-HTP will be assessed across three different participant groups: i) subacute (6 months-1 year) AIS A/B SCI individuals, ii) chronic (>2 years post injury) AIS A/B SCI individuals and iii) chronic AIS C/D SCI individuals.. In a placebo-controlled, randomized crossover design, participants will receive i) 50 mg 5HTP combined with 50 mg carbidopa, ii) 100 mg 5-HTP combined with 50 mg carbidopa, iii) 50 mg carbidopa only or iv) placebo. Ten participants will be recruited in each group. Participants will visit the lab on four separate occasions, separated by at least 72 hours.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Jessica D'Amico, PhD; Phone Number: 780-735-7917; Email: damico1@ualberta.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G-2E1
      • Recruiting
      • University of Alberta
      • Contact: Jessica D'Amico, PhD; Phone Number: 780-735-7917; Email: damico1@ualberta.ca
      • Principal Investigator: Monica A Gorassini, PhD
      • Principal Investigator: Lalith Satkunam, MD
• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40292
      • Completed
      • University of Louisville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• participants must have suffered trauma to the spinal cord at least six months ago or longer

Exclusion Criteria:

• individuals with damage to the nervous system other than to the spinal cord
• pregnant and/or breastfeeding women
• alcoholic participants
• history of seizure/epilepsy
• history of suicidal thoughts or behaviors
• known or suspected allergy to the medication ingredients
• cardiovascular disease including history of heart attack or heart rhythm irregularities
• coronary artery disease
• reduced liver function or disease
• reduced kidney function or disease
• lung disease
• comatose or depressed states due to CNS depressants
• endocrine dysfunction
• blood dyscrasias or blood related disease
• bone marrow depression
• hypocalcemia
• history of stomach ulcers
• wide angle glaucoma
• phenylketonuria
• history of tumors
• uncontrolled heart problems
• unstable psychiatric or mental disorder

Participants taking:

• monoamine oxidase inhibitor therapy
• serotonergic antidepressants
• tricyclic antidepressants
• any type of serotonergic agonist
• dopamine D2 receptor antagonists
• amphetamine
• CNS depressants
• levodopa
• lithium
• anti-hypertensive drugs
• iron salts
• metoclopramide
• phenothiazine medication

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo comparator	Drug: Placebo; Placebo
Active Comparator: Low-dose 5HTP; 50mg 5-HTP in combination with 50mg carbidopa	Drug: 5-Hydroxytryptophan; 50mg combined with 50mg carbidopa; Drug: Carbidopa; 50mg
Active Comparator: High-dose 5HTP; 100mg 5-HTP in combination with 50mg carbidopa	Drug: Carbidopa; 50mg; Drug: 5-Hydroxytryptophan 100 MG; 100mg combined with 50mg carbidopa
Sham Comparator: Carbidopa; 50mg carbidopa only	Drug: Carbidopa; 50mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in motoneuron excitability	F waves	Pre drug-intake, 30minutes, 60minutes, 90minutes and 120minutes post drug-intake
Change in spinal excitability	H reflex	Pre drug-intake, 30minutes, 60minutes, 90minutes and 120minutes post drug-intake
Change in flexor reflex/spasms	Cutaneomuscular reflex	Pre drug-intake, 30minutes, 60minutes, 90minutes and 120minutes post drug-intake
Change in functional movement performance	Leg cycling task	Pre drug-intake, 120-150minutes post drug-intake

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum analysis of 5HIAA (UofL Cohort only)	5-HIAA (serum)	90-120minutes post drug-intake
Serum analysis of serotonin (UofL Cohort only)	5-HT (serum and whole blood), cortisol	90-120minutes post drug-intake
Serum analysis of cortisol (UofL Cohort only)	serum cortisol	90-120minutes post drug-intake
Whole blood analysis of Serotonin (UofL Cohort only)	Blood 5HT	90-120minutes post drug-intake

Collaborators and Investigators

• Sponsor: University of Alberta
• Collaborators: Wings for Life
• Investigators: Principal Investigator: Jessica D'Amico, PhD, University of Alberta

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: August 17, 2020
• First Submitted That Met QC Criteria: August 17, 2020
• First Posted (Actual): August 20, 2020

Study Record Updates

• Last Update Posted (Estimated): August 27, 2025
• Last Update Submitted That Met QC Criteria: August 20, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Spinal Cord Injuries; Amino Acids, Peptides, and Proteins; Organic Chemicals; Substandard Drugs; Pharmaceutical Preparations; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amines; Amino Acids; Catechols; Phenols; Benzene Derivatives; Amino Acids, Aromatic; Amino Acids, Cyclic; Catecholamines; Tryptophan; Methyldopa; Dihydroxyphenylalanine; Hydrazines; Carbidopa; 5-Hydroxytryptophan; Counterfeit Drugs
• Other Study ID Numbers: Pro00119483/00125176

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No