Effects of 5HTP on the Injured Human Spinal Cord

Spinal Cord Injuries Clinical Trial

— 5-HTP only  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04520178
• Other study ID #: Pro00119483/00125176
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: July 1, 2020
• Est. completion date: December 30, 2024

Study information

• Verified date: August 2023
• Source: University of Alberta
• Contact: Jessica D'Amico, PhD
• Phone: 780-735-7917
• Email: damico1[@]ualberta.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Spinal Cord Injuries

Intervention

Drug:
• 5-Hydroxytryptophan 100 MG
100mg combined with 50mg carbidopa
• 5-Hydroxytryptophan
50mg combined with 50mg carbidopa
• Carbidopa
50mg
• Placebo
Placebo

Locations

Country	Name	City	State
Canada	University of Alberta	Edmonton	Alberta
United States	University of Louisville	Louisville	Kentucky

Sponsors (2)

Lead Sponsor	Collaborator
University of Alberta	Wings for Life

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in motoneuron excitability	F waves	Pre drug-intake, 30minutes, 60minutes, 90minutes and 120minutes post drug-intake
Primary	Change in spinal excitability	H reflex	Pre drug-intake, 30minutes, 60minutes, 90minutes and 120minutes post drug-intake
Primary	Change in flexor reflex/spasms	Cutaneomuscular reflex	Pre drug-intake, 30minutes, 60minutes, 90minutes and 120minutes post drug-intake
Primary	Change in functional movement performance	Leg cycling task	Pre drug-intake, 120-150minutes post drug-intake
Secondary	Serum analysis of 5HIAA (UofL Cohort only)	5-HIAA (serum)	90-120minutes post drug-intake
Secondary	Serum analysis of serotonin (UofL Cohort only)	5-HT (serum and whole blood), cortisol	90-120minutes post drug-intake
Secondary	Serum analysis of cortisol (UofL Cohort only)	serum cortisol	90-120minutes post drug-intake
Secondary	Whole blood analysis of Serotonin (UofL Cohort only)	Blood 5HT	90-120minutes post drug-intake