StrokeNCT05832567
Mechanisms of Open and Hidden Placebo in Stroke Recovery
A study testing Active rTMS in people with Stroke and Hemiparesis, run by Spaulding Rehabilitation Hospital at 1 site in United States.
Trial summary
This trial aims to investigate whether placebo in isolation (open and hidden) has a specific neural signature in stroke subjects thus providing a novel mechanism to explain placebo effects that can be used to ultimately enhance stroke rehabilitation therapies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke, Hemiparesis
- What is being tested?
- Active rTMS
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Sep 2023to 30 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults with hemiparesis due to chronic stroke
- Stroke duration of 6 months or more
- Fugl-Meyer scale upper extremity motor assessment score of > 11 and ≤ 56
- Pre-stroke disability (defined as a score of < 3 on the Modified Rankin Scale)
- Age 18 or older
Who cannot join
- Stroke of anterior cerebral artery territory with prefrontal lesion and stroke-related decreased EEG power in the prefrontal cortex
- Unable to understand instructions
- TMS contraindications: electronic hardware in close contact to the discharging coil such as cochlear implant, internal pulse generator or medical pump
- Concurrent unstable medical conditions
- A score of 24 or higher on the Hamilton Depression Rating Scale (HDRS)
- Joint or paretic extremity pain likely to interfere with assessments
- Pregnancy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Spaulding Hospital Cambridge
Cambridge, Massachusetts, 02138
Elly Pichardo, MD, 617-952-6158, epichardo@partners.org
Felipe Fregni, MD, PhD, MPH
About this study
This trial aims to investigate whether placebo in isolation (open and hidden) has a specific neural signature in stroke subjects thus providing a novel mechanism to explain placebo effects that can be used to ultimately enhance stroke rehabilitation therapies.
Read the detailed description
Placebo effect leads to significant effects on brain excitability and connectivity, ultimately influencing clinical outcomes, including motor learning in stroke. This trial will provide critical mechanistic data to improve the understanding of placebo in stroke clinical trials, as to solve methodological and ethical dilemma in research designs, and to improve its clinical outcomes. It aims to investigate whether placebo in isolation (open and hidden) has a specific neural signature in stroke subjects. For this purpose, the investigators plan to recruit 56 chronic stroke participants, that will be randomized using blocked randomization in a 2:2:2:1 proportion to one of the following groups, respectively: 1) open placebo (OP) alone (16 subjects); 2) sham rTMS alone (16 subjects); 3) no intervention (16 subjects); or 4) active rTMS alone (8 subjects). All four groups will undergo 2 weeks of daily intervention visits (10 sessions).
- Conditions
- Stroke, Hemiparesis
- Being tested
- Active rTMS, Sham rTMS, Open Placebo
- Keywords
- stroke, placebo
- Medical subject headings
- Stroke, Paresis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active rTMSDevice
Subjects will undergo repetitive transcranial magnetic stimulation, each session lasting 20 minutes.
Sham rTMSDevice
Subjects will undergo sham repetitive transcranial magnetic stimulation, each session lasting 20 minutes.
Open PlaceboDietary supplement
The open placebo will consist of an inactive substance pill commonly used in clinical trials and given to the subject in a regular pill dispenser.
| Study group | Role | What they receive |
|---|---|---|
| Active rTMS | Active comparator | The participant will receive a session of low frequency rTMS to the contralesional primary motor cortex. Low frequency rTMS stimulation will be applied according to the following parameter: intensity of 80% MT (intensity could be adjusted if not comfortable to the subject), frequency of 1 Hz, 1200 pulses as a single, continuous train lasting 20 minutes. Receives: Device: Active rTMS |
| Sham rTMS | Sham comparator | The investigators will place the coil in the same location, usually used for the active stimulation with the same stimulation parameters. However, the investigators will replace the active coil with a sham coil to ensure no stimulation is provided. Receives: Device: Sham rTMS |
| Open Placebo | Placebo comparator | The open placebo will consist of typical prescription medicine bottle of placebo pills with a label clearly marked "placebo pills" "take 2 pills twice daily." The placebo pills are made from Microcrystalline Cellulose. Receives: Dietary Supplement: Open Placebo |
| No Intervention | No intervention | It consists of treatment-as-usual group. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Electroencephalography (EEG): Frontal alpha asymmetry
The FAA score will be calculated by subtracting the natural log-transformed alpha power in the left frontal region (F3, F7, Fp1) from the natural log-transformed power in the right frontal region (F4, F8, Fp2).
Measured: Change from 2 weeks to baseline
Secondary outcomes (2)
Fugl-Meyer motor scale (FM)
The investigators will use this tool for motor function after stroke. It is valid, responsive to change, and widely used for motor function and recovery assessment in stroke patients. Items are scored on a 3-point ordinal scale, being 0 the lowest and 2 the highest value. A higher score means a better outcome.
Measured: Change from 2 weeks to baseline
Premotor-M1 (PM-M1) connectivity
For the PM-M1 connectivity computation, the investigators will calculate the spectral coherence score, which indicates the functional connectivity in brain activity between two cortical regions and is calculated as a function of frequency.
Measured: Change from 2 weeks to baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2023
- Study start11 Sep 2023
- Primary completion1 Jun 2026
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Spaulding Rehabilitation Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Felipe Fregni, MD, PhD, MPH, Spaulding Rehabilitation Hospital
- Investigators
- Felipe Fregni, MD, PhD, MPH, Principal investigator, Spaulding Rehabilitation Hospital/Harvard Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05832567
- Sponsor's protocol ID
- 2023P000884
- Status last verified
- Jul 2026
- First submitted
- 24 Mar 2023
- Last updated
- 14 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Ortega-Marquez J, Camargo L, Gianlorenco AC, Sosa W, Black-Schaffer R, Wang QM, Fregni F. Mechanisms of open and hidden placebo in stroke recovery: targeting neuroplasticity insights of the placebo effect - study protocol for a controlled, parallel, randomised clinical trial. BMJ Open. 2026 Jul 22;16(7):e113119. doi: 10.1136/bmjopen-2025-113119.
PubMed 42486522
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Open and Hidden Placebo in Stroke Recovery
- ClinicalTrials.gov ID
- NCT05832567
- Acronym / sponsor ID
- 2023P000884
- Conditions
- Stroke, Hemiparesis
- Keywords
- stroke, placebo
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- Spaulding Rehabilitation HospitalUniversity, hospital or other
- Study start
- 11 Sep 2023 (actual)
- Primary completion
- 1 Jun 2026 (actual)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 27 Apr 2023 (actual)
- 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.
This trial aims to investigate whether placebo in isolation (open and hidden) has a specific neural signature in stroke subjects thus providing a novel mechanism to explain placebo effects that can be used to ultimately enhance stroke rehabilitation therapies.
Detailed description
Placebo effect leads to significant effects on brain excitability and connectivity, ultimately influencing clinical outcomes, including motor learning in stroke. This trial will provide critical mechanistic data to improve the understanding of placebo in stroke clinical trials, as to solve methodological and ethical dilemma in research designs, and to improve its clinical outcomes. It aims to investigate whether placebo in isolation (open and hidden) has a specific neural signature in stroke subjects. For this purpose, the investigators plan to recruit 56 chronic stroke participants, that will be randomized using blocked randomization in a 2:2:2:1 proportion to one of the following groups, respectively: 1) open placebo (OP) alone (16 subjects); 2) sham rTMS alone (16 subjects); 3) no intervention (16 subjects); or 4) active rTMS alone (8 subjects). All four groups will undergo 2 weeks of daily intervention visits (10 sessions).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Active rTMS | Active comparator | Device: Active rTMSThe participant will receive a session of low frequency rTMS to the contralesional primary motor cortex. Low frequency rTMS stimulation will be applied according to the following parameter: intensity of 80% MT (intensity could be adjusted if not comfortable to the subject), frequency of 1 Hz, 1200 pulses as a single, continuous train lasting 20 minutes. |
| Sham rTMS | Sham comparator | Device: Sham rTMSThe investigators will place the coil in the same location, usually used for the active stimulation with the same stimulation parameters. However, the investigators will replace the active coil with a sham coil to ensure no stimulation is provided. |
| Open Placebo | Placebo comparator | Dietary Supplement: Open PlaceboThe open placebo will consist of typical prescription medicine bottle of placebo pills with a label clearly marked "placebo pills" "take 2 pills twice daily." The placebo pills are made from Microcrystalline Cellulose. |
| No Intervention | No intervention | –It consists of treatment-as-usual group. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adults with hemiparesis due to chronic stroke
- Stroke duration of 6 months or more
- Fugl-Meyer scale upper extremity motor assessment score of > 11 and ≤ 56
- Pre-stroke disability (defined as a score of < 3 on the Modified Rankin Scale)
- Age 18 or older
Key exclusion criteria (7 listed)
- Stroke of anterior cerebral artery territory with prefrontal lesion and stroke-related decreased EEG power in the prefrontal cortex
- Unable to understand instructions
- TMS contraindications: electronic hardware in close contact to the discharging coil such as cochlear implant, internal pulse generator or medical pump
- Concurrent unstable medical conditions
- A score of 24 or higher on the Hamilton Depression Rating Scale (HDRS)
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 rTMSSubjects will undergo repetitive transcranial magnetic stimulation, each session lasting 20 minutes. | Device | Active rTMS |
| Sham rTMSSubjects will undergo sham repetitive transcranial magnetic stimulation, each session lasting 20 minutes. | Device | Sham rTMS |
| Open PlaceboThe open placebo will consist of an inactive substance pill commonly used in clinical trials and given to the subject in a regular pill dispenser. | Dietary supplement | Open Placebo |
Primary outcome
Electroencephalography (EEG): Frontal alpha asymmetry
Time frame: Change from 2 weeks to baseline
The FAA score will be calculated by subtracting the natural log-transformed alpha power in the left frontal region (F3, F7, Fp1) from the natural log-transformed power in the right frontal region (F4, F8, Fp2).
2 secondary outcomes
Fugl-Meyer motor scale (FM)
Time frame: Change from 2 weeks to baseline
Premotor-M1 (PM-M1) connectivity
Time frame: Change from 2 weeks to baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2026.
- Derived from this study: PubMed 42486522Ortega-Marquez J, Camargo L, Gianlorenco AC, Sosa W, Black-Schaffer R, Wang QM, Fregni F. Mechanisms of open and hidden placebo in stroke recovery: targeting neuroplasticity insights of the placebo effect - study protocol for a controlled, parallel, randomised clinical trial. BMJ Open. 2026 Jul 22;16(7):e113119. doi: 10.1136/bmjopen-2025-113119.
- Individual participant dataSharing planned: No
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Web-Based Tele-Rehabilitation Using Action Observation and Mirror Therapy for Subacute Stroke: A Randomized Controlled Trial
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Early Motor-Cognitive Integrative Training on Cognitive and Motor Performance in Patients With Aneurysmal Subarachnoid Hemorrhage
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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.
Felipe Fregni, MD, PhD, MPH principal investigator
Spaulding Rehabilitation Hospital/Harvard Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active rTMS in people with Stroke and Hemiparesis, run by Spaulding Rehabilitation Hospital 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 5 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 14 Jul 2026. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Felipe Fregni, MD, PhD, MPH (6179526156, fregni.felipe@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Electroencephalography (EEG): Frontal alpha asymmetry (time frame: Change from 2 weeks to baseline). 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 NCT05832567, which also lists 1 linked publication.
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 14 Jul 2026.