TMS and Exercise for Post-stroke Pain

• ClinicalTrials.gov Identifier: NCT04672044
• Recruitment Status: Recruiting
• First Posted: December 17, 2020
• Last Update Posted: December 12, 2023
• Sponsor: VA Office of Research and Development
• Information provided by (Responsible Party): VA Office of Research and Development

Tracking Information

• First Submitted Date: December 11, 2020
• First Posted Date: December 17, 2020
• Last Update Posted Date: December 12, 2023
• Actual Study Start Date: January 14, 2022
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 11, 2020)

Visual Analogue Scale for Pain [ Time Frame: through study completion, an average of 12 weeks ]

The visual analog scale (VAS) is a validated, subjective measure for pain. Scores are based on self-reported measures of symptoms that are recorded with a single handwritten mark placed at one point along the length of a 10-cm line that represents a continuum between the two ends of the scale-"no pain" on the left end (0 cm) of the scale and the "worst pain" on the right end of the scale (10 cm)

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: December 11, 2020)

modified Rankin Scale [ Time Frame: through study completion, an average of 12 weeks ]

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

1. No significant disability despite symptoms; able to carry out all usual duties and activities
2. Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
3. Moderate disability; requiring some help, but able to walk without assistance
4. Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance
5. Severe disability; bedridden, incontinent and requiring constant nursing care and attention
6. Dead

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: TMS and Exercise for Post-stroke Pain
• Official Title: Feasibility of Combination Exercise and Neuromodulation Rehabilitation to Improve Post-stroke Chronic Pain
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Feasibility of a double-blind sham-controlled intervention

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Double-blind

Primary Purpose: Treatment

• Condition: Chronic Post-stroke Headache

Intervention

• Device: Active rTMS and exercise
  active
• Combination Product: Sham rTMS+Exercise
  sham

Study Arms

• Active Comparator: active rTMS+Exercise
  active rTMS
  Intervention: Device: Active rTMS and exercise
• Sham Comparator: sham rTMS+Exercise
  sham rTMS
  Intervention: Combination Product: Sham rTMS+Exercise

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 11, 2020): 32
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2024
• Estimated Primary Completion Date: June 30, 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 19 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Chen Lin, MD; (205) 933-8101; Chen.Lin@va.gov

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04672044
• Other Study ID Numbers: B3612-P; I21RX003612 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: VA Office of Research and Development
• Original Responsible Party: Same as current
• Current Study Sponsor: VA Office of Research and Development
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Chen Lin, MD; Birmingham VA Medical Center, Birmingham, AL

• PRS Account: VA Office of Research and Development
• Verification Date: December 2023