TMS and Exercise for Post-stroke Pain

Feasibility of Combination Exercise and Neuromodulation Rehabilitation to Improve Post-stroke Chronic Pain

There are over 7 million people living with stroke in the United States. Per year, approximately 17,000 Veterans are admitted to the VA for acute stroke. Chronic pain after stroke can occur between 10-50% of stroke survivors. Post-stroke pain (PSP) can lead to further complications in a stroke survivor's recovery. Exercise has improved PSP and associated symptoms such as mobility, fatigue, and quality of life. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique using electromagnetic induction for cortical neurostimulation. The use of rTMS has been explored shown to be effective in treating chronic PSP but is limited in effect duration. Our proposal will test the hypothesis that rTMS is feasible and safe to be paired with exercise. Additionally, the investigators believe a complementary effect can develop to enhance the neurostimulation duration of rTMS.

Study Overview

• Status: Completed
• Conditions: Chronic Post-stroke Headache
• Intervention / Treatment: Device: Active rTMS and exercise; Combination product: Sham rTMS+Exercise

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233-1927
      • Birmingham VA Medical Center, Birmingham, AL

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female Veteran of US military 19 years of age
• Signed informed consent
• Minimum of 3-months since time of stroke and medically stable
• Headache has persisted for >3 months after stabilization of the stroke
• Ability to walk or tolerate recumbent cycle ergometry for 10 mins without assistance
• Stable pain medication regimen for 1 month prior to study
• Females of child-bearing potential (i.e. not postmenopausal or surgically sterile) must be using a medically acceptable method of birth control and should not be pregnant nor have plans for pregnancy or breastfeeding during the study
• Completed diagnostic, maximal graded exercise test including 12-lead ECG and indirect calorimetry (i.e. oxygen uptake, minute ventilation, respiratory exchange ratio, etc.)
• Minimum pain intensity of 30 on the Mechanical Visual Analogue Scale on average with pain symptoms.

Exclusion Criteria:

• Moderate to severe cognitive impairment (Montreal Cognitive Assessment score <16/30)
• Pre-stroke modified Rankin >2
• History of seizures
• Presence of any standard TMS or MRI contraindications (see human subjects)
• Current diagnosis of DSM-5-defined bipolar disorder I, schizophrenia, schizoaffective disorder, or obsessive-compulsive disorder
• Diagnosis of moderate or severe substance use disorder (except for caffeine and nicotine) during the preceding 3 months (Participants must agree to abstain from illicit drugs during the study)
• Increased risk of suicide that necessitates inpatient treatment or warrants additional therapy excluded by the protocol; and/or intensity of suicidal ideation (Type 4 or Type 5) or any suicidal behavior in the past 3 months on Columbia Suicide Severity Rating Scale (C-SSRS)

• Litigating for compensation for a psychiatric disorder

  • Veterans who are in the process of applying for or receiving VA service-connected disability are eligible
• Current enrollment in another intervention trial for pain or stroke
• Persons imprisoned, of minor age, diagnosed with terminal illness, or require surrogate for consent
• Fails baseline exercise screening activities
• Persistent post-stroke headaches not better accounted for by another diagnosis
• Is unable to reliably attend intervention sessions i.e. planning to move, transportation issues
• Neurological disorder pre- or post- stroke affecting subject's ability to follow study directions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: active rTMS+Exercise; active rTMS	Device: Active rTMS and exercise; active
Sham Comparator: sham rTMS+Exercise; sham rTMS	Combination product: Sham rTMS+Exercise; sham

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Modified Rankin Scale From Baseline to Follow-up 30 Days After Last Intervention	The modified Ranking scale (mRS) is a single-item, global, Likert-type scale ranging from 0-6 (higher scores mean a worse outcome) to categorize level of functional independence with comparison to pre-stroke function, accounting for activities of daily living. Participants were scored at baseline and 30 days after last intervention.	From baseline to follow-up 30 days after last intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified Rankin Scale	Measures the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. Score Description: 0 No symptoms at all; No significant disability despite symptoms; able to carry out all usual duties and activities; Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance; Moderate disability; requiring some help, but able to walk without assistance; Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance; Severe disability; bedridden, incontinent and requiring constant nursing care and attention; Dead	through study completion, an average of 12 weeks

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Chen Lin, MD, Birmingham VA Medical Center, Birmingham, AL

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2022
• Primary Completion (Actual): December 30, 2024
• Study Completion (Actual): December 30, 2024

Study Registration Dates

• First Submitted: December 11, 2020
• First Submitted That Met QC Criteria: December 11, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Actual): June 15, 2025
• Last Update Submitted That Met QC Criteria: June 13, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Vascular Headaches; post-stroke headache
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Headache
• Other Study ID Numbers: B3612-P; I21RX003612 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No