StrokeEarly Phase 1NCT03020433
Novel Brain Stimulation Therapies in Stroke Guided Expressions of Plasticity
A Early Phase 1 study testing rTMS Contralesional M1, rTMS Contralesional PMC and rTMS Ipsilesional PMC in people with Stroke and Cerebrovascular Disorders, run by The Cleveland Clinic at 1 site in United States.
Trial summary
The investigators ultimate goal is to personalize brain stimulation for stroke so outcomes of the upper limb can be maximized for each individual patient. Several groups including the investigators have recently theorized that personalizing stimulation so as to selectively stimulate iM1 in mild, and cPMd in patients… Read more about this study
- Who is it for?
- Ages 21 years and olderHealthy volunteers can take part
- Conditions the study is for
- Stroke, Cerebrovascular Disorders, Nervous System Diseases
- What is being tested?
- rTMS Contralesional M1, rTMS Contralesional PMC and rTMS Ipsilesional PMC
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2016to Dec 2019
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 21 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- greater than 21 years old
- more than 6 months from first, unilateral index stroke
- unilateral paresis of the upper limb indexed as greater than or equal to 20% slowness in functional reaching compared to non-paretic limb
- UEFM less than or equal to 61 out of 66.
Who cannot join
- subjects who cannot perform reaching with shoulder
- severe cognitive deficit (less than or equal to 24 on Mini-Mental State examination.
- contraindication to TMS or MRI including: seizures, ongoing use of certain neuro- or psycho-active medications, implants, or pacemaker.
- currently receiving outpatient therapy.
Trial locations and contacts
1 site in 1 country.
About this study
The investigators ultimate goal is to personalize brain stimulation for stroke so outcomes of the upper limb can be maximized for each individual patient. Several groups including the investigators have recently theorized that personalizing stimulation so as to selectively stimulate iM1 in mild, and cPMd in patients with greater severity would help generalize benefits of stimulation. The investigator premise that variances in expressions of plasticity can explain how to best stratify patients for robust, personalized stimulation.
Read the detailed description
AIMS: The ultimate goal is to personalize brain stimulation for stroke so outcomes of the upper limb can be maximized for each individual patient. Even though stimulation is one of the most well studied methods to augment plasticity and boost recovery, it is still not approved for outpatient therapy. Benefits of stimulation are weak and variable especially in patients who suffer from greater damage and disability. The key limitation of the standard approach is its generic assumptions about plasticity. The current standard assumes that ipsilesional primary motor cortex (iM1) can impact recovery for patients in all ranges of severity, and intact, contralesional cortices always compete with iM1 to inhibit recovery. But, these long-standing assumptions fail to consider that iM1 or its pathways are damaged in a majority (58-83%) of patients. As such, the potential of iM1 would be weak and variable, and patients will have little option but to rely on plasticity of intact, contralesional cortices that are more likely to survive. Of all surviving cortices, contralesional dorsal premotor cortex (cPMd) expresses plasticity most consistently. cPMd is activated in movement of the paretic limb when activating iM1 is less likely. cPMd even reduces its competition with iM1 and offers its ipsilateral pathways instead to support recovery of the proximal paretic limb when pathways from iM1 are largely damaged.
Several groups including the investigator have recently theorized that personalizing stimulation so as to selectively stimulate iM1 in mild, and cPMd in patients with greater severity would help generalize benefits of stimulation. These theoretical claims, however, remain untested since several gaps exist. For instance, what is the cut-off level of severity that stratifies those who respond to stimulation of iM1 from those who respond to stimulation of cPMd? Even then, are substrates for 'personalized' stimulation same as the substrates that express plasticity in recovery, i.e. if patients benefit from stimulation of cPMd, do they express contralesional plasticity in recovery? Here, the investigator premise that variances in expressions of plasticity can explain how to best stratify patients for robust, personalized stimulation.
- Conditions
- Stroke, Cerebrovascular Disorders, Nervous System Diseases, Brain Diseases, Cardiovascular Diseases, Vascular Diseases
- Being tested
- rTMS Contralesional M1, rTMS Contralesional PMC, rTMS Ipsilesional PMC, rTMS sham at Ipsilesional M1
- Keywords
- Stroke, rehab, rehabilitation, paresis, paralysis, stroke therapy, CVA, cerebrovascular accident, brain diseases, TMS, transcranial magnetic stimulation, CIMT, constraint induced movement therapy, MRI
- Medical subject headings
- Stroke, Cerebrovascular Disorders, Nervous System Diseases, Brain Diseases, Cardiovascular Diseases, Vascular Diseases, Central Nervous System Diseases, Paresis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rTMS Contralesional M1Device
1Hz Contalesional M1 repetitive transcranial magnetic stimulation (1500 pulses, 25 minutes, 90% AMT
rTMS Contralesional PMCDevice
5Hz Contralesional PMC repetitive transcranial magnetic stimulation (1500 pulses, 10 minutes, 5 trains of 300 pulses each with 1 minute rest in between, 90% AMT)
rTMS Ipsilesional PMCDevice
5HZ Ipsilesional PMC repetitive transcranial magnetic stimulation (1500 pulses, 10 minutes, 5 trains of 300 pulses each with 1 minute rest in between, 90% AMT)
rTMS sham at Ipsilesional M1Device
1Hz Ipsilesional M1 sham repetitive transcranial magnetic stimulation (1500 pulses, 25 minutes, 50% MSO)
| Study group | Role | What they receive |
|---|---|---|
| rTMS Contralesional M1 Inhibition | Active comparator | Not described Receives: Device: rTMS Contralesional M1 |
| rTMS Contralesional PMC facilitation | Active comparator | Not described Receives: Device: rTMS Contralesional PMC |
| rTMS Ipsilesional PMC facilitation | Active comparator | Not described Receives: Device: rTMS Ipsilesional PMC |
| rTMS Sham at Ipsilesional M1 | Sham comparator | Not described Receives: Device: rTMS sham at Ipsilesional M1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Aim 1: Change in time (seconds) to perform functional reaching
Patients will be seated with test arm resting on a table. Three buttons (labeled 1, 2, 3) will be arranged in a semi-circle at 80% of reaching distance of the paretic limb. A number (1, 2, or 3) will cue patients to reach and push the designated button as fast as possible using shoulder flexion-abduction and elbow extension while their trunk is stabilized. Three blocks of 20 trials will be tested pre- and post-rTMS.
Measured: Change in functional reaching from baseline to post rTMS, assessed for approximately 4-6 hours.
Secondary outcomes (1)
Aim 2:Change in plasticity evoked with rTMS.
Expressions of plasticity will be noted for ipsilesional vs. contralesional pathways and inhibition imposed on ipsilesional cortices from contralesional cortices. Subjects will be stratified based on which stimulation location evoked the most plasticity from each of the arms.
Measured: Change in neurophysiology from baseline to post rTMS assessed for approximately 4-6 hours.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2017 (estimated)
- Study startMar 2016
- Primary completionDec 2019
- Study completionDec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe 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
- Early Phase 1
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ela B. Plow, The Cleveland Clinic
- Investigators
- Ela Plow, PhD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03020433
- Sponsor's protocol ID
- 16-128
- Other IDs
- 16GRNT27720019
- Status last verified
- Jul 2020
- First submitted
- 6 Sep 2016
- Last updated
- 16 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Brain Stimulation Therapies in Stroke Guided Expressions of Plasticity
- ClinicalTrials.gov ID
- NCT03020433
- Acronym / sponsor ID
- 16-128
- Conditions
- Stroke, Cerebrovascular Disorders, Nervous System Diseases, Brain Diseases, Cardiovascular Diseases, Vascular Diseases
- Keywords
- Stroke, rehab, rehabilitation, paresis, paralysis, stroke therapy, CVA, cerebrovascular accident
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Study start
- Mar 2016 (actual)
- Primary completion
- Dec 2019 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 13 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators ultimate goal is to personalize brain stimulation for stroke so outcomes of the upper limb can be maximized for each individual patient. Several groups including the investigators have recently theorized that personalizing stimulation so as to selectively stimulate iM1 in mild, and cPMd in patients with greater severity would help generalize benefits of stimulation. The investigator premise that variances in expressions of plasticity can explain how to best stratify patients for robust, personalized stimulation.
Detailed description
AIMS: The ultimate goal is to personalize brain stimulation for stroke so outcomes of the upper limb can be maximized for each individual patient. Even though stimulation is one of the most well studied methods to augment plasticity and boost recovery, it is still not approved for outpatient therapy. Benefits of stimulation are weak and variable especially in patients who suffer from greater damage and disability. The key limitation of the standard approach is its generic assumptions about plasticity. The current standard assumes that ipsilesional primary motor cortex (iM1) can impact recovery for patients in all ranges of severity, and intact, contralesional cortices always compete with iM1 to inhibit recovery. But, these long-standing assumptions fail to consider that iM1 or its pathways are damaged in a majority (58-83%) of patients. As such, the potential of iM1 would be weak and variable, and patients will have little option but to rely on plasticity of intact, contralesional cortices that are more likely to survive. Of all surviving cortices, contralesional dorsal premotor cortex (cPMd) expresses plasticity most consistently. cPMd is activated in movement of the paretic limb when activating iM1 is less likely. cPMd even reduces its competition with iM1 and offers its ipsilateral pathways instead to support recovery of the proximal paretic limb when pathways from iM1 are largely damaged.
Several groups including the investigator have recently theorized that personalizing stimulation so as to selectively stimulate iM1 in mild, and cPMd in patients with greater severity would help generalize benefits of stimulation. These theoretical claims, however, remain untested since several gaps exist. For instance, what is the cut-off level of severity that stratifies those who respond to stimulation of iM1 from those who respond to stimulation of cPMd? Even then, are substrates for 'personalized' stimulation same as the substrates that express plasticity in recovery, i.e. if patients benefit from stimulation of cPMd, do they express contralesional plasticity in recovery? Here, the investigator premise that variances in expressions of plasticity can explain how to best stratify patients for robust, personalized stimulation.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| rTMS Contralesional M1 Inhibition | Active comparator | Device: rTMS Contralesional M1 |
| rTMS Contralesional PMC facilitation | Active comparator | Device: rTMS Contralesional PMC |
| rTMS Ipsilesional PMC facilitation | Active comparator | Device: rTMS Ipsilesional PMC |
| rTMS Sham at Ipsilesional M1 | Sham comparator | Device: rTMS sham at Ipsilesional M1 |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- greater than 21 years old
- more than 6 months from first, unilateral index stroke
- unilateral paresis of the upper limb indexed as greater than or equal to 20% slowness in functional reaching compared to non-paretic limb
- UEFM less than or equal to 61 out of 66.
Key exclusion criteria (4 listed)
- subjects who cannot perform reaching with shoulder
- severe cognitive deficit (less than or equal to 24 on Mini-Mental State examination.
- contraindication to TMS or MRI including: seizures, ongoing use of certain neuro- or psycho-active medications, implants, or pacemaker.
- currently receiving outpatient therapy.
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 |
|---|---|---|
| rTMS Contralesional M11Hz Contalesional M1 repetitive transcranial magnetic stimulation (1500 pulses, 25 minutes, 90% AMT | Device | rTMS Contralesional M1 Inhibition |
| rTMS Contralesional PMC5Hz Contralesional PMC repetitive transcranial magnetic stimulation (1500 pulses, 10 minutes, 5 trains of 300 pulses each with 1 minute rest in between, 90% AMT) | Device | rTMS Contralesional PMC facilitation |
| rTMS Ipsilesional PMC5HZ Ipsilesional PMC repetitive transcranial magnetic stimulation (1500 pulses, 10 minutes, 5 trains of 300 pulses each with 1 minute rest in between, 90% AMT) | Device | rTMS Ipsilesional PMC facilitation |
| rTMS sham at Ipsilesional M11Hz Ipsilesional M1 sham repetitive transcranial magnetic stimulation (1500 pulses, 25 minutes, 50% MSO) | Device | rTMS Sham at Ipsilesional M1 |
Primary outcome
Aim 1: Change in time (seconds) to perform functional reaching
Time frame: Change in functional reaching from baseline to post rTMS, assessed for approximately 4-6 hours.
Patients will be seated with test arm resting on a table. Three buttons (labeled 1, 2, 3) will be arranged in a semi-circle at 80% of reaching distance of the paretic limb. A number (1, 2, or 3) will cue patients to reach and push the designated button as fast as possible using shoulder flexion-abduction and elbow extension while their trunk is stabilized. Three blocks of 20 trials will be tested pre- and post-rTMS.
1 secondary outcome
Aim 2:Change in plasticity evoked with rTMS.
Time frame: Change in neurophysiology from baseline to post rTMS assessed for approximately 4-6 hours.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2020.
- 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.
Ela Plow, PhD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing rTMS Contralesional M1, rTMS Contralesional PMC and rTMS Ipsilesional PMC in people with Stroke and Cerebrovascular Disorders, run by The Cleveland Clinic 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 4 inclusion and 4 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 16 Jul 2020. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Aim 1: Change in time (seconds) to perform functional reaching (time frame: Change in functional reaching from baseline to post rTMS, assessed for approximately 4-6 hours.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Jul 2020.