NCT05708274

Brief Summary

The purpose of this study is to investigate the short-term effects of 3 approved FDA drugs (cyproheptadine (CPH), carbidopa-levodopa (CD-LD), and atomoxetine (ATX)) on motor responses when delivered in combination with hand training exercises in people with chronic spinal cord injury. The goal is to learn how to better strengthen connections between the brain and spinal cord after spinal cord injury, and if this connection is improved by one(or more) of the drugs. Multiple aspects of nerve transmission and muscle response will be measured via noninvasive brain and spinal cord stimulation, along with motor performance (dexterity and strength).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
25

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Jan 2023

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 27, 2022

Completed
24 days until next milestone

Study Start

First participant enrolled

January 20, 2023

Completed
12 days until next milestone

First Posted

Study publicly available on registry

February 1, 2023

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 30, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 30, 2025

Completed
Last Updated

December 8, 2025

Status Verified

December 1, 2025

Enrollment Period

2.8 years

First QC Date

December 27, 2022

Last Update Submit

December 1, 2025

Conditions

Spinal Cord Injuries

Keywords

Transcranial magnetic stimulationPharmacological agentsTranscutaneous spinal cord stimulationHand exercise

Outcome Measures

Primary Outcomes (1)

  • Assessing task performance (dexterity)

    Unilateral manual dexterity will be assessed using the 9-Hole Peg Test (Aim 1a).

    Assess change from baseline to 10 minutes after completion of drug+task training.

Secondary Outcomes (12)

  • Assessing task performance (dexterity)

    Assess change from baseline to 10 minutes after completion of drug+task training.

  • Assessing volitional grip strength

    Assess change from baseline to 10 minutes after completion of drug+task training.

  • Assessing volitional pinch strength

    Assess change from baseline to 10 minutes after completion of drug+task training.

  • Assessing corticospinal plasticity

    Assess change from baseline to 10 minutes after completion of drug+task training.

  • Assessing cortical plasticity

    Assess change from baseline to 10 minutes after completion of drug+task training.

  • +7 more secondary outcomes

Study Arms (4)

CPH + hand training

EXPERIMENTAL

A single dose of Cyproheptadine (CPH) (8 mg) will be administered. Supplied as 2 over-encapsulated pills of 4 mg each.

Drug: CPH + hand training

CD-LD + hand training

EXPERIMENTAL

A single dose of IR Carbidopa-levodopa (CD-LD) (50/200 mg) will be administered. Supplied as 2 over-encapsulated pills (25 mg carbidopa / 100 mg levodopa each).

Drug: CD-LD + hand training

ATX + hand training

EXPERIMENTAL

A single dose of Atomoxetine (ATX) (40 mg) will be administered. Supplied as 1 over-encapsulated pill of 40 mg plus 1 placebo capsule.

Drug: ATX + hand training

Placebo + hand training

PLACEBO COMPARATOR

A single dose of Placebo will be administered. Supplied as 2 gelatin capsules, identical in number, size, shape and color, filled with microcrystalline cellulose.

Drug: Placebo + hand training

Interventions

CPH + hand trainingDRUG

Following a 10-minute rest after baseline measurements a single dose pharmacological agent or placebo will be administered, in blinded fashion, with up to 180 mL of noncarbonated water, on an empty stomach (minimum 2 hours without food). After capsule ingestion, participants will spend 50 minutes performing hand task-oriented training, resting for 10 minutes before undertaking post-intervention outcome measurements.

CPH + hand training
CD-LD + hand trainingDRUG

Following a 10-minute rest after baseline measurements a single dose pharmacological agent or placebo will be administered, in blinded fashion, with up to 180 mL of noncarbonated water, on an empty stomach (minimum 2 hours without food). After capsule ingestion, participants will spend 50 minutes performing hand task-oriented training, resting for 10 minutes before undertaking post-intervention outcome measurements.

CD-LD + hand training
ATX + hand trainingDRUG

Following a 10-minute rest after baseline measurements a single dose pharmacological agent or placebo will be administered, in blinded fashion, with up to 180 mL of noncarbonated water, on an empty stomach (minimum 2 hours without food). After capsule ingestion, participants will spend 50 minutes performing hand task-oriented training, resting for 10 minutes before undertaking post-intervention outcome measurements.

ATX + hand training
Placebo + hand trainingDRUG

Following a 10-minute rest after baseline measurements a single dose pharmacological agent or placebo will be administered, in blinded fashion, with up to 180 mL of noncarbonated water, on an empty stomach (minimum 2 hours without food). After capsule ingestion, participants will spend 50 minutes performing hand task-oriented training, resting for 10 minutes before undertaking post-intervention outcome measurements.

Placebo + hand training

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female between 18 and 65 years of age; clinically stable chronic (\> 12 months) SCI at or above C8 spinal segment;
  • Motor-incomplete with a score of 2 or more (out of 5) on manual muscle testing (MMT) of finger extension, finger flexion, or finger abduction in left or right hand(s); or able to perform thumb-index finger pinch of the left or right hand;
  • Detectable stimulation-evoked muscle responses of the left or right first dorsal interosseous (FDI) and/or abductor pollicis brevis (APB); Detectable FDI/APB surface electromyography (EMG) muscle activity during thumb-index finger pinch;
  • Must have stable: medication \[≥ 30 days prior\]; rehabilitation regimen \[≥ 15 days prior\];
  • Must be able to: abstain from alcohol, smoking and caffeine consumption on the day prior/of each experiment; abstain from recreational drugs for the entirety of the study; commit to study requirements (i.e., 7 visits); provide informed consent.

You may not qualify if:

  • History of moderate or severe head trauma (loss of consciousness for greater than one hour or evidence of brain contusion or hemorrhage or depressed skull fracture on prior imaging);
  • History of other serious central or peripheral neurological injury;
  • History of implanted brain/spine/nerve stimulators, aneurysm clips, ferromagnetic metallic implants in the head (except inside mouth); cochlear implants; cardiac pacemaker/defibrillator; intracardiac lines; currently increased intracranial pressure; or other contraindications to brain stimulation or task performance;
  • Ventilator dependence or patent tracheostomy site;
  • Unstable syrinx, or multiple spinal cord lesions;
  • Unclear diagnosis; History of stroke, brain tumor, brain abscess, or multiple sclerosis;
  • Personal history of seizures; extensive family history of seizures; use of medications that lower seizure threshold (e.g., amphetamines, dalfampridine, and bupropion);
  • Use of the study medications; Use of medications known to have significant adverse interactions with the study medication as described in the manufacturers' prescribing information \[14 days prior\]; previous allergic reaction or hypersensitivity to study drug(s);
  • Presence of a medical condition that represents a risk for study drug(s) administration; evidence of liver disease or clinical jaundice; neutropenia; glaucoma; gastrointestinal ulcer(s); active malignancy; undiagnosed skin lesions; autoimmune disorders; chronic infectious diseases (e.g. HIV, hepatitis B or C); pregnancy or nursing mothers (a pregnancy urine test may be warranted); neurologic disorders (including a history of serious head trauma or seizures), and uncontrolled cardiovascular, metabolic, pulmonary or renal disease; premorbid, ongoing major depression or psychosis, altered cognitive status; bipolar disorder; suicidal ideation or past suicide attempts;
  • History of severe hearing problems, loss or tinnitus;
  • Presence of urinary infection, fever, pressure ulcer; or open skin lesions (shoulders or arms);
  • Recent history (\< 6 months) of recurrent autonomic dysreflexia, defined as a syndrome of sudden rise in systolic pressure greater than 20 mm Hg or diastolic pressure greater than 10 mm Hg, without rise in HR, accompanied by symptoms such as headache, facial flushing, sweating, nasal congestion, and blurry vision (closely monitored during all testing procedures);
  • Heavy alcohol consumption (greater than equivalent of 5 oz of liquor) within previous 48 hours;
  • Recent history (\>1 year) of chemical substance dependency or significant psychosocial disturbance;
  • Study participation of an investigational drug or device \[60 days prior\];
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

James J. Peters Veterans Affairs Medical Center

The Bronx, New York, 10468, United States

Location

MeSH Terms

Conditions

Spinal Cord Injuries

Interventions

Carboxypeptidase H

Condition Hierarchy (Ancestors)

Spinal Cord DiseasesCentral Nervous System DiseasesNervous System DiseasesTrauma, Nervous SystemWounds and Injuries

Intervention Hierarchy (Ancestors)

CarboxypeptidasesExopeptidasesPeptide HydrolasesHydrolasesEnzymesEnzymes and CoenzymesMetalloexopeptidasesMetalloproteasesProprotein Convertases

Study Officials

  • Lynda M Murray, PhD

    Bronx VA Medical Center / James J. Peters Veterans Affairs Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Model Details: Double-blind, placebo-controlled, single-dose, randomized crossover investigation to one of four conditions: 1) CPH + hand training; 2) CD-LD + hand training; 3) ATX + hand training; and 4) placebo + hand training, performed at least a week apart. Outcomes measures will be assessed before and 60 minutes after study drug administration.
Sponsor Type
FED
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor

Study Record Dates

First Submitted

December 27, 2022

First Posted

February 1, 2023

Study Start

January 20, 2023

Primary Completion

October 30, 2025

Study Completion

October 30, 2025

Last Updated

December 8, 2025

Record last verified: 2025-12

Data Sharing

IPD Sharing
Will share

Deidentified, individual-level data will be deposited to appropriate public repositories, such as Open Data Commons for Spinal Cord Injury (https://scicrunch.org/odc-sci), Figshare, or others. This will allow more powerful meta-analysis of disparate smaller studies, a need which is even more urgent in neurorehabilitation than in other fields that are more amenable to large drug studies.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
Within 6 months of manuscript preparation.
Access Criteria
Authorization, Informed Consent, and an appropriate written agreement limiting use of the data to the conditions described in the authorization and consent. A Data Use Agreement (DUA) will indicate adherence to any applicable Informed Consent provisions, and prohibits the recipient from identifying or re-identifying any individual whose data are included in the dataset.

Locations

US(1)