Mechanisms of Open and Hidden Placebo in Stroke Recovery

NCT ID: NCT05832567

Last Updated: 2025-09-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-11
• Study Completion Date: 2026-06-30

Brief 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Active rTMS

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.

Group Type: ACTIVE_COMPARATOR

Active rTMS

Intervention Type: DEVICE

Subjects will undergo repetitive transcranial magnetic stimulation, each session lasting 20 minutes.

Sham rTMS

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.

Group Type: SHAM_COMPARATOR

Sham rTMS

Intervention Type: DEVICE

Subjects will undergo sham repetitive transcranial magnetic stimulation, each session lasting 20 minutes.

Open Placebo

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.

Group Type: PLACEBO_COMPARATOR

Open Placebo

Intervention Type: DIETARY_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.

No Intervention

It consists of treatment-as-usual group.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Active rTMS

Subjects will undergo repetitive transcranial magnetic stimulation, each session lasting 20 minutes.

Intervention Type: DEVICE

Sham rTMS

Subjects will undergo sham repetitive transcranial magnetic stimulation, each session lasting 20 minutes.

Intervention Type: DEVICE

Open Placebo

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.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

1. Adults with hemiparesis due to chronic stroke

2. Stroke duration of 6 months or more

3. Fugl-Meyer scale upper extremity motor assessment score of > 11 and ≤ 56

4. Pre-stroke disability (defined as a score of < 3 on the Modified Rankin Scale)

5. Age 18 or older

Exclusion Criteria

1. Stroke of anterior cerebral artery territory with prefrontal lesion and stroke-related decreased EEG power in the prefrontal cortex

2. Unable to understand instructions

3. TMS contraindications: electronic hardware in close contact to the discharging coil such as cochlear implant, internal pulse generator or medical pump

4. Concurrent unstable medical conditions

5. A score of 24 or higher on the Hamilton Depression Rating Scale (HDRS)

6. Joint or paretic extremity pain likely to interfere with assessments

7. Pregnancy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Spaulding Rehabilitation Hospital

OTHER

Sponsor Role: lead

Responsible Party

Felipe Fregni, MD, PhD, MPH

Director of Spaulding Neuromodulation Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Felipe Fregni, MD, PhD, MPH

Role: PRINCIPAL_INVESTIGATOR

Spaulding Rehabilitation Hospital/Harvard Medical School

Locations

Spaulding Hospital Cambridge

Cambridge, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Felipe Fregni, MD, PhD, MPH

Role: CONTACT

fregni.felipe@mgh.harvard.edu

6179526156

Elly Pichardo, MD

Role: CONTACT

epichardo@partners.org

6179526154

Facility Contacts

Elly Pichardo, MD

Role: primary

epichardo@partners.org

617-952-6158

Other Identifiers

2023P000884

Identifier Type: -

Identifier Source: org_study_id