Motor and Neurophysiological Changes After Ischemic Conditioning in Healthy and Individuals With Stroke

Sponsor

University of Illinois at Chicago (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05906602

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The goal of this clinical trial is to test ischemic conditioning (blood flow restriction) as a cortical priming modality to improve gait function in stroke. Cortical priming, a procedure that augments excitability in the brain prior to or during motor training, is emerging as a promising adjunct strategy to facilitate changes in brain activity and improve motor behavior following a neurological injury such as stroke.

The main questions it aims to answer are:

At what time point during a single session of ischemic conditioning do neuromodulatory effects in the lower limb motor cortex take place?
Can ischemic conditioning be used as a cortical priming modality to improve walking function in stroke when compared to aerobic exercise?

Participants will take part in two sessions of ischemic conditioning where a cuff (similar to ones that measure blood pressure) will be placed on the thigh and inflated to one of two blood flow restriction pressures (real or sham). Each participant will experience measures of brain activity before, during, and after both sessions of ischemic conditioning. Individuals with stroke will participate in one additional session of aerobic exercise.

Researchers will compare ischemic conditioning and aerobic exercise as cortical priming modalities in stroke to see if they produce similar changes in brain activity and similar performances on subsequent motor behavior tasks.

Condition or Disease	Intervention/Treatment	Phase
Stroke	Device: Real Ischemic Conditioning Device: Sham Ischemic Conditioning Other: Aerobic Exercise	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

Single (Participant)

Masking Description:

Participants will be masked to the type of ischemic conditioning they receive (real or sham). Session order will be randomized.

Primary Purpose:

Treatment

Official Title:

Motor and Neurophysiological Changes After Ischemic Conditioning in Healthy and Individuals With Stroke

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Individuals with Stroke Will participate in ischemic conditioning and aerobic exercise.	Device: Real Ischemic Conditioning While seated, a rapid inflation cuff, similar to those used to measure blood pressure, will be placed on the nondominant or paretic thigh to perform real ischemic conditioning. The pressure of the cuff will be increased for 5 minutes followed by no pressure for 5 minutes, repeated 5 times for a total of 50 minutes. Device: Sham Ischemic Conditioning While seated, a rapid inflation cuff, similar to those used to measure blood pressure, will be placed on the nondominant or paretic thigh to perform sham or fake ischemic conditioning. The pressure of the cuff will be increased for 5 minutes followed by no pressure for 5 minutes, repeated 5 times for a total of 50 minutes. Other: Aerobic Exercise Pending the results of a screening session to determine the proper exercise modality for participants' physical abilities, participants will perform interval-based aerobic exercise either on a treadmill or recumbent stepper. During aerobic exercise sessions, participants will perform intervals of intense exercise interleaved with rest/ active recovery.
Experimental: Young Healthy Adults Will participate in ischemic conditioning.	Device: Real Ischemic Conditioning While seated, a rapid inflation cuff, similar to those used to measure blood pressure, will be placed on the nondominant or paretic thigh to perform real ischemic conditioning. The pressure of the cuff will be increased for 5 minutes followed by no pressure for 5 minutes, repeated 5 times for a total of 50 minutes. Device: Sham Ischemic Conditioning While seated, a rapid inflation cuff, similar to those used to measure blood pressure, will be placed on the nondominant or paretic thigh to perform sham or fake ischemic conditioning. The pressure of the cuff will be increased for 5 minutes followed by no pressure for 5 minutes, repeated 5 times for a total of 50 minutes.

Arm

Intervention/Treatment

Experimental: Individuals with Stroke

Will participate in ischemic conditioning and aerobic exercise.

Device: Real Ischemic Conditioning

While seated, a rapid inflation cuff, similar to those used to measure blood pressure, will be placed on the nondominant or paretic thigh to perform real ischemic conditioning. The pressure of the cuff will be increased for 5 minutes followed by no pressure for 5 minutes, repeated 5 times for a total of 50 minutes.

Device: Sham Ischemic Conditioning

While seated, a rapid inflation cuff, similar to those used to measure blood pressure, will be placed on the nondominant or paretic thigh to perform sham or fake ischemic conditioning. The pressure of the cuff will be increased for 5 minutes followed by no pressure for 5 minutes, repeated 5 times for a total of 50 minutes.

Other: Aerobic Exercise

Pending the results of a screening session to determine the proper exercise modality for participants' physical abilities, participants will perform interval-based aerobic exercise either on a treadmill or recumbent stepper. During aerobic exercise sessions, participants will perform intervals of intense exercise interleaved with rest/ active recovery.

Experimental: Young Healthy Adults

Will participate in ischemic conditioning.

Device: Real Ischemic Conditioning

Device: Sham Ischemic Conditioning

Outcome Measures

Primary Outcome Measures

Change in corticomotor excitability for young healthy adults [Changes in corticomotor excitability will be calculated within and between sessions at baseline, during IC intervals, immediate-post, and 30-minutes-post both IC sessions (real and sham).]
Excitability of the primary lower limb motor cortex will be assessed using single pulse transcranial magnetic stimulation (TMS) and motor evoked potentials (MEPs) will be recorded from the tibialis anterior muscles of the nondominant leg.
Change in corticomotor excitability for individuals with stroke [Changes in corticomotor excitability will be calculated within and between sessions at baseline, immediate-post, and 30-minutes-post one session of sham IC, real IC, and aerobic exercise.]
Excitability of the primary lower limb motor cortex will be assessed using single pulse transcranial magnetic stimulation (TMS) and motor evoked potentials (MEPs) will be recorded from the tibialis anterior muscles of the paretic leg.
Change in intracortical inhibition for young healthy adults [Changes in intracortical inhibition will be calculated within and between sessions at baseline, immediate-post, and 30-minutes-post both IC sessions (real and sham).]
Intracortical inhibition will be assessed using paired-pulse transcranial magnetic stimulation (TMS) and motor evoked potentials (MEPs) will be recorded from the tibialis anterior muscles of the nondominant leg.
Change in intracortical inhibition for individuals with stroke [Changes in intracortical inhibition will be calculated within and between sessions at baseline, immediate-post, and 30-minutes-post one session of sham IC, real IC, and aerobic exercise.]
Intracortical inhibition will be assessed using paired-pulse transcranial magnetic stimulation (TMS) and motor evoked potentials (MEPs) will be recorded from the tibialis anterior muscles of the paretic leg.
Change in transcallosal inhibition for young healthy adults [Changes in transcallosal inhibition will be calculated within and between sessions at baseline, immediate-post, and 30-minutes-post both IC sessions (real and sham).]
Inhibition from the stimulated hemisphere to the non-stimulated hemisphere will be quantified as a measure of the ipsilateral silent period (iSP) using single pulse transcranial magnetic stimulation (TMS) and motor evoked potentials (MEPs) will be recorded from the tibialis anterior muscle of the leg ipsilateral to TMS stimulation.
Change in transcallosal inhibition for individuals with stroke [Changes in transcallosal inhibition will be calculated within and between sessions at baseline, immediate-post, and 30-minutes-post one session of sham IC, real IC, and aerobic exercise.]
Inhibition from the stimulated hemisphere to the non-stimulated hemisphere will be quantified as a measure of the ipsilateral silent period (iSP) using single pulse transcranial magnetic stimulation (TMS) and motor evoked potentials (MEPs) will be recorded from the tibialis anterior muscle of the leg ipsilateral to TMS stimulation.
Change in gait speed for individuals with stroke [Changes in gait speed will be calculated within and between sessions at baseline, immediate-post, and 30-minutes-post one session of sham IC, real IC, and aerobic exercise.]
For individuals with stroke only, self-selected and fast walking will be measured as the average of 3 trials of the 10-meter walk test (10MWT).
Change in ankle motor control for individuals with stroke [Changes in ankle motor control will be calculated within and between sessions at baseline, immediate-post, and 30-minutes-post one session of sham IC, real IC, and aerobic exercise.]
For individuals with stroke only, reaction time will be measured using a choice reaction time task involving rapid ankle dorsiflexion and plantarflexion movements in a custom built ankle-tracking device.
Change in lower limb strength for individuals with stroke [Changes in strength will be calculated within and between sessions at baseline, immediate-post, and 30-minutes-post one session of sham IC, real IC, and aerobic exercise.]
For individuals with stroke only, participants will perform 3 trials each of maximum ankle dorsiflexion and plantarflexion strength.

Secondary Outcome Measures

Numerical Rating Scale (NRS) for Pain [During each real and sham ischemic conditioning session, pain scores will be reported for each participant during intervals of blow flow restriction and reperfusion through study completion, an average of 1 year.]
For young healthy adults and individuals with stroke, subjective measures of pain will be reported during ischemic conditioning using a Numerical Rating Scale (NRS) from 0 (no pain) to 10 (worst pain).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Young Healthy Adults:

Inclusion Criteria:

18 - 35 years of age
No history of neurological impairment

Exclusion Criteria:

Pre-existing neurological condition
Contraindications to TMS or IC

Individuals with Stroke:

Inclusion Criteria:

Single, monohemispheric stroke > 3 months since onset
Residual hemiparetic gait deficits (e.g., abnormal gait pattern)
Able to walk on the treadmill or cycle on the recumbent stepper

Exclusion Criteria:

Lesions affecting the brainstem or cerebellum
Severe osteoporosis
Other neurological disorders that may interfere with motor function
Presence of uncontrolled medical conditions (I.e., uncontrolled hypertension, untreated cardiac/ heart disease, or untreated pulmonary/ lung disease)
Diagnosis of severe renal (kidney) or hepatic (liver) disease
Unhealed decubiti, persistent infections that may interfere with ability to perform test procedures
Failure to pass the Physical Activity Readiness Questionnaire
Significant cognitive or communication impairment which could impede the understanding of the purpose of study procedures
Contraindications to TMS or IC

TMS General Exclusion Criteria:

Previous adverse reaction to TMS
Skull abnormalities or fractures
Concussion within the last 6 months
Unexplained, recurring headaches
Implanted cardiac pacemaker
Metal implants in the head or face
History of seizures or epilepsy
Use of medications that could alter cortical excitability or increase risk of seizure (e.g., antidepressants, antipsychotics, anxiolytics, anticonvulsants)
Current pregnancy

IC General Exclusion Criteria:

Deep vein thrombosis
Peripheral arterial grafts in the lower extremity
Blood clots in the leg, or any condition in which compression of the thigh or short-term blood flow restriction is contraindicated (e.g., open wounds in the leg)
Presence of uncontrolled hypertension, peripheral vascular disease, or hematological disease

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

University of Illinois at Chicago

Investigators

Principal Investigator: Sangeetha Madhavan, PT, PhD, University of Illinois at Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Sangeetha Madhavan, Professor, Physical Therapy, University of Illinois at Chicago

ClinicalTrials.gov Identifier:

NCT05906602

Other Study ID Numbers:

2022-1620

First Posted:

Jun 18, 2023

Last Update Posted:

Jun 18, 2023

Last Verified:

Jun 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Stroke

Study Results

No Results Posted as of Jun 18, 2023