TMS and Exercise for Post-stroke Pain

NCT ID: NCT04672044

Last Updated: 2025-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-14
• Study Completion Date: 2024-12-30

Brief Summary

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.

Conditions

Chronic Post-stroke Headache

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

active rTMS+Exercise

active rTMS

Group Type: ACTIVE_COMPARATOR

Active rTMS and exercise

Intervention Type: DEVICE

active

sham rTMS+Exercise

sham rTMS

Group Type: SHAM_COMPARATOR

Sham rTMS+Exercise

Intervention Type: COMBINATION_PRODUCT

sham

Interventions

Active rTMS and exercise

active

Intervention Type: DEVICE

Sham rTMS+Exercise

sham

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

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

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chen Lin, MD

Role: PRINCIPAL_INVESTIGATOR

Birmingham VA Medical Center, Birmingham, AL

Locations

Birmingham VA Medical Center, Birmingham, AL

Birmingham, Alabama, United States

Countries

United States

References

Lin C, Morgan CJ, Fortenberry ELS, Androulakis XM, McGregor K. The safety and feasibility of a pilot randomized clinical trial using combined exercise and neurostimulation for post-stroke pain: the EXERT-Stroke study. Front Neurol. 2025 Apr 24;16:1524004. doi: 10.3389/fneur.2025.1524004. eCollection 2025.

Reference Type: DERIVED

PMID: 40343185 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

I21RX003612

Identifier Type: NIH

Identifier Source: secondary_id

View Link

B3612-P

Identifier Type: -

Identifier Source: org_study_id