Effects of 5HTP and LDOPA on CNS Excitability After SCI

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

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.

Study Overview

• Status: Suspended
• Conditions: Spinal Cord Injuries
• Intervention / Treatment: Drug: Placebo oral tablet; Drug: Carbidopa; Drug: 5HTP; Drug: L-DOPA

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

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville, Kentucky Spinal Cord Injury Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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
Sham Comparator: Effects of single-dose of carbidopa (50mg) on CNS excitability; 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; Carbidopa (50mg)
Placebo Comparator: Effects of single-dose placebo on CNS Excitability; 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; Placebo
Active Comparator: Effects of single-dose 5HTP/carbidopa on CNS Excitability; 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; 5HTP/carbidopa (50-200 mg 5-HTP/50 mg carbidopa); Other Names: carbidopa
Active Comparator: Effects of single-dose L-DOPA/carbidopa on CNS Excitability; 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; L-DOPA/carbidopa (50-200 mg L-DOPA/50 mg carbidopa); Other Names: Sinemet; Carbidopa

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jessica M D'Amico
• Investigators: Principal Investigator: Jessica D'Amico, PhD, University of Louisville

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2019
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: June 19, 2019
• First Submitted That Met QC Criteria: June 25, 2019
• First Posted (Actual): June 27, 2019

Study Record Updates

• Last Update Posted (Actual): October 17, 2022
• Last Update Submitted That Met QC Criteria: October 13, 2022
• Last Verified: October 1, 2022

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; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Aromatic Amino Acid Decarboxylase Inhibitors; Carbidopa
• Other Study ID Numbers: 18.1268

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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