Finding the Best Combination of Brain and Spinal Cord Stimulation With Hand Training After Spinal Cord Injury

Sponsor

Bronx VA Medical Center (U.S. Fed)

Overall Status

Not yet recruiting

CT.gov ID

NCT06104735

Collaborator

Bronx Veterans Medical Research Foundation, Inc (Other), New York State Department of Health (Other)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

While physical exercise remains the foundation for any rehabilitation therapy, we seek to improve the benefits of exercise by combining it with the concept of "Fire Together, Wire Together" - when brain stimulation is synchronized with spinal cord stimulation, nerve circuits in the spinal cord strengthen - we call this "Spinal Cord Associative Plasticity", or SCAP.

This project will build on our promising preliminary findings. When one pulse of brain stimulation is synchronized with one pulse of cervical spinal stimulation, hand muscle responses are larger than with brain stimulation alone or unsynchronized stimulation. However, we do not know the best ways to apply SCAP repetitively, especially in conjunction with exercise, to increase and extend improvements in clinical function. Do ideal intervention parameters vary across individuals, or do they need to be customized?

We will take a systematic approach with people who have chronic cervical SCI to determine each person's best combination of SCAP with task-oriented hand exercise. Participants will undergo roughly 50 intervention, verification, and follow-up sessions over 6 to 10 months each. We will measure clinical and physiological responses of hand and arm muscles to each intervention.

Regaining control over hand function represents the top priority for individuals with cervical SCI. Furthermore, this approach could be compatible with other future interventions, including medications and cell-based treatments.

Condition or Disease	Intervention/Treatment	Phase
Spinal Cord Injuries	Procedure: Synaptic Pairing Interval Procedure: Frequency Procedure: Bouts Procedure: Spacing Procedure: Exercise Procedure: SCAP plus Exercise	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Each participant will undergo multiple conditions and verifications in an "n-of-1" design.Each participant will undergo multiple conditions and verifications in an "n-of-1" design.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Optimizing Spinal Cord Associative Plasticity to Enhance Response to Hand Training in Cervical Spinal Cord Injury

Anticipated Study Start Date :

Jan 1, 2024

Anticipated Primary Completion Date :

Nov 1, 2026

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: All participants Each participant will undergo varying conditions in separate phases to determine optimal: Pairing interval; Frequency; Number of bouts, Inter-bout spacing, and the order of SCAP when given in conjunction with task-oriented hand exercise.	Procedure: Synaptic Pairing Interval Optimize interstimulus pairing between brain and spinal cord stimulation. Procedure: Frequency Compare 2 Hz continuous to intermittent theta burst frequency Procedure: Bouts Compare effects of 1, 2, or 4 bouts of SCAP Procedure: Spacing Compare 6 versus 12 minutes of rest in between bouts of SCAP Procedure: Exercise Task-oriented hand exercises Procedure: SCAP plus Exercise Compare interleaved versus serial bouts of SCAP and exercise.

Arm

Intervention/Treatment

Experimental: All participants

Each participant will undergo varying conditions in separate phases to determine optimal: Pairing interval; Frequency; Number of bouts, Inter-bout spacing, and the order of SCAP when given in conjunction with task-oriented hand exercise.

Procedure: Synaptic Pairing Interval

Optimize interstimulus pairing between brain and spinal cord stimulation.

Procedure: Frequency

Compare 2 Hz continuous to intermittent theta burst frequency

Procedure: Bouts

Compare effects of 1, 2, or 4 bouts of SCAP

Procedure: Spacing

Compare 6 versus 12 minutes of rest in between bouts of SCAP

Procedure: Exercise

Task-oriented hand exercises

Procedure: SCAP plus Exercise

Compare interleaved versus serial bouts of SCAP and exercise.

Outcome Measures

Primary Outcome Measures

Amplitude of motor evoked potential at the first dorsal interosseous muscle. [2 hours]
The primary neurophysiological outcome will be corticospinal excitability measured at the FDI muscle. TMS recruitment curves will be collected. The amplitude of FDI muscle response at "S50" (the recruitment curve's half-maximal point) will be compared after the various interventions.

Secondary Outcome Measures

Pinch and grip strength [2 hours]
Maximal isometric pinch strength will be measured in key-pinch (lateral edge of the index finger and the thumb) and tip-to-tip (tips of first and third finger) configurations using a pinch dynamometer. Grip strength will be measured using a hand dynamometer. For each type of pinch or grip, three trials will be conducted by holding the dynamometer with maximal volitional force for 3-5 seconds, with at least 30 seconds or more between trials. The highest achieved value will be used for analysis.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age between 18-85 years.
Must have stable prescription medication for 30 days prior to screening.
Must be able to abstain from alcohol, smoking and heavy caffeine consumption on the day of each experiment.
Must be able to commit to study requirements (i.e., 53 visits over 6-10 months).

provide informed consent.

Score of 1-4 (out of 5) on manual muscle testing of finger extension, finger flexion, or finger abduction in left or right hand.

Exclusion Criteria:

Personal or extensive family history of seizures;
Ventilator dependence or patent tracheostomy site;
Use of medications that significantly lower seizure threshold, such as amphetamines, neuroleptics, dalfampridine, and bupropion;
History of stroke, brain tumor, brain abscess, or multiple sclerosis;
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 implanted brain/spine/nerve stimulators, aneurysm clips, ferromagnetic metallic implants in the head (except for inside mouth); cochlear implants; cardiac pacemaker/defibrillator; intracardiac lines; currently increased intracranial pressure; or other contraindications to brain or spine stimulation;
Significant coronary artery or cardiac conduction disease; recent history of myocardial infarction and heart failure with an ejection fraction of less than 30% or with a New York Heart Association Functional Classification of Class III or IV;
Recent history (within past 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 heart rate, accompanied by symptoms such as headache, facial flushing, sweating, nasal congestion, and blurry vision (this will be closely monitored during all screening and testing procedures);
History of significant hearing problems;
History of bipolar disorder;
History of suicide attempt;
Active psychosis;
Recent history (>1 year) of chemical substance dependency or significant psychosocial disturbance;
Heavy alcohol consumption (greater than equivalent of 5oz of liquor) within previous 48 hours;
Open skin lesions over the face, neck, shoulders, or arms;
Pregnancy; and
Unsuitable for study participation as determined by study physician.