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

Primary Purpose

Spinal Cord Injuries

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
5-Hydroxytryptophan 100 MG
5-Hydroxytryptophan
Carbidopa
Placebo
Sponsored by
University of Alberta
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Spinal Cord Injuries

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Louisville
  • University of AlbertaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Sham Comparator

Placebo Comparator

Arm Label

Low-dose 5HTP

High-dose 5HTP

Carbidopa

Placebo

Arm Description

50mg 5-HTP in combination with 50mg carbidopa

100mg 5-HTP in combination with 50mg carbidopa

50mg carbidopa only

Placebo comparator

Outcomes

Primary Outcome Measures

Change in motoneuron excitability
F waves
Change in spinal excitability
H reflex
Change in flexor reflex/spasms
Cutaneomuscular reflex
Change in functional movement performance
Leg cycling task

Secondary Outcome Measures

Serum analysis of 5HIAA (UofL Cohort only)
5-HIAA (serum)
Serum analysis of serotonin (UofL Cohort only)
5-HT (serum and whole blood), cortisol
Serum analysis of cortisol (UofL Cohort only)
serum cortisol
Whole blood analysis of Serotonin (UofL Cohort only)
Blood 5HT

Full Information

First Posted
August 17, 2020
Last Updated
August 3, 2023
Sponsor
University of Alberta
Collaborators
Wings for Life
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1. Study Identification

Unique Protocol Identification Number
NCT04520178
Brief Title
Effects of 5HTP on the Injured Human Spinal Cord
Acronym
5-HTP only
Official Title
Effects of the Serotonin Precursor, 5-hydroxytryptophan, in the Injured Human Spinal Cord
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2020 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
December 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Alberta
Collaborators
Wings for Life

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Cord Injuries

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 2, Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Low-dose 5HTP
Arm Type
Active Comparator
Arm Description
50mg 5-HTP in combination with 50mg carbidopa
Arm Title
High-dose 5HTP
Arm Type
Active Comparator
Arm Description
100mg 5-HTP in combination with 50mg carbidopa
Arm Title
Carbidopa
Arm Type
Sham Comparator
Arm Description
50mg carbidopa only
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo comparator
Intervention Type
Drug
Intervention Name(s)
5-Hydroxytryptophan 100 MG
Intervention Description
100mg combined with 50mg carbidopa
Intervention Type
Drug
Intervention Name(s)
5-Hydroxytryptophan
Intervention Description
50mg combined with 50mg carbidopa
Intervention Type
Drug
Intervention Name(s)
Carbidopa
Intervention Description
50mg
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Change in motoneuron excitability
Description
F waves
Time Frame
Pre drug-intake, 30minutes, 60minutes, 90minutes and 120minutes post drug-intake
Title
Change in spinal excitability
Description
H reflex
Time Frame
Pre drug-intake, 30minutes, 60minutes, 90minutes and 120minutes post drug-intake
Title
Change in flexor reflex/spasms
Description
Cutaneomuscular reflex
Time Frame
Pre drug-intake, 30minutes, 60minutes, 90minutes and 120minutes post drug-intake
Title
Change in functional movement performance
Description
Leg cycling task
Time Frame
Pre drug-intake, 120-150minutes post drug-intake
Secondary Outcome Measure Information:
Title
Serum analysis of 5HIAA (UofL Cohort only)
Description
5-HIAA (serum)
Time Frame
90-120minutes post drug-intake
Title
Serum analysis of serotonin (UofL Cohort only)
Description
5-HT (serum and whole blood), cortisol
Time Frame
90-120minutes post drug-intake
Title
Serum analysis of cortisol (UofL Cohort only)
Description
serum cortisol
Time Frame
90-120minutes post drug-intake
Title
Whole blood analysis of Serotonin (UofL Cohort only)
Description
Blood 5HT
Time Frame
90-120minutes post drug-intake

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jessica D'Amico, PhD
Phone
780-735-7917
Email
damico1@ualberta.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jessica D'Amico, PhD
Organizational Affiliation
University of Alberta
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40292
Country
United States
Individual Site Status
Completed
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G-2E1
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jessica D'Amico, PhD
Phone
780-735-7917
Email
damico1@ualberta.ca
First Name & Middle Initial & Last Name & Degree
Monica A Gorassini, PhD
First Name & Middle Initial & Last Name & Degree
Lalith Satkunam, MD

12. IPD Sharing Statement

Learn more about this trial

Effects of 5HTP on the Injured Human Spinal Cord

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