Chronic Post-stroke HeadachePhase 1NCT04672044
TMS and Exercise for Post-stroke Pain
A Phase 1 study testing Active rTMS and exercise in people with Chronic Post-stroke Headache, run by VA Office of Research and Development at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Chronic Post-stroke Headache
- What is being tested?
- Active rTMS and exercise
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jan 2022to 30 Dec 2024
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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)
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Birmingham VA Medical Center, Birmingham, AL
Birmingham, Alabama, 35233-1927
About this study
Official title: 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.
- Conditions
- Chronic Post-stroke Headache
- Being tested
- Active rTMS and exercise, Sham rTMS+Exercise
- Keywords
- Vascular Headaches, post-stroke headache
- Medical subject headings
- Vascular Headaches
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active rTMS and exerciseDevice
active
Sham rTMS+ExerciseCombination product
sham
| Study group | Role | What they receive |
|---|---|---|
| active rTMS+Exercise | Active comparator | active rTMS Receives: Device: Active rTMS and exercise |
| sham rTMS+Exercise | Sham comparator | sham rTMS Receives: Combination Product: Sham rTMS+Exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From baseline to follow-up 30 days after last intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2020
- Study start14 Jan 2022
- Primary completion30 Dec 2024
- Study completion30 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Post-stroke HeadacheStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Feasibility of a double-blind sham-controlled intervention
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Chen Lin, MD, Principal investigator, Birmingham VA Medical Center, Birmingham, AL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04672044
- Sponsor's protocol ID
- B3612-P
- Other IDs
- I21RX003612
- Status last verified
- Jun 2025
- First submitted
- 11 Dec 2020
- Last updated
- 15 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Dagli C, Morgan CJ, McGregor K, Lin C. Pain Outcomes and Exercise Data from the EXERT-Stroke Pilot Clinical Trial on Post-Stroke Headaches. Restor Neurol Neurosci. 2026 Sep 10:9226028261486597. doi: 10.1177/09226028261486597. Online ahead of print.
PubMed 42720582Lin 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.
PubMed 40343185
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility of Combination Exercise and Neuromodulation Rehabilitation to Improve Post-stroke Chronic Pain
- ClinicalTrials.gov ID
- NCT04672044
- Acronym / sponsor ID
- B3612-P
- Conditions
- Chronic Post-stroke Headache
- Keywords
- Vascular Headaches, post-stroke headache
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 14 Jan 2022 (actual)
- Primary completion
- 30 Dec 2024 (actual)
- Study completion
- 30 Dec 2024 (actual)
- First posted
- 17 Dec 2020 (actual)
- Results
- Posted 15 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Feasibility of a double-blind sham-controlled intervention
| Arm | Type | Receives |
|---|---|---|
| active rTMS+Exercise | Active comparator | Device: Active rTMS and exerciseactive rTMS |
| sham rTMS+Exercise | Sham comparator | Combination Product: Sham rTMS+Exercisesham rTMS |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active rTMS and exerciseactive | Device | active rTMS+Exercise |
| Sham rTMS+Exercisesham | Combination product | sham rTMS+Exercise |
Primary outcome
Change in Modified Rankin Scale From Baseline to Follow-up 30 Days After Last Intervention
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42720582Dagli C, Morgan CJ, McGregor K, Lin C. Pain Outcomes and Exercise Data from the EXERT-Stroke Pilot Clinical Trial on Post-Stroke Headaches. Restor Neurol Neurosci. 2026 Sep 10:9226028261486597. doi: 10.1177/09226028261486597. Online ahead of print.
- Derived from this study: PubMed 40343185Lin 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chen Lin, MD principal investigator
Birmingham VA Medical Center, Birmingham, AL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Active rTMS and exercise in people with Chronic Post-stroke Headache, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Modified Rankin Scale From Baseline to Follow-up 30 Days After Last Intervention (time frame: From baseline to follow-up 30 days after last intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04672044, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2025.