Mechanisms of Open and Hidden Placebo in Stroke Recovery

NCT05832567 | Recruiting DMC FDA Device

• 1 other identifier: 2023P000884
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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.

Conditions

Stroke; Hemiparesis

Keywords

stroke; placebo

Outcome Measures

Primary Outcomes (1)

• 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).

  Change from 2 weeks to baseline

Secondary Outcomes (2)

• Fugl-Meyer motor scale (FM)

  Change from 2 weeks to baseline

• Premotor-M1 (PM-M1) connectivity

  Change from 2 weeks to baseline

Study Arms (4)

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.

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.

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.

Dietary Supplement: Open Placebo

No Intervention

NO INTERVENTION

It consists of treatment-as-usual group.

Interventions

Active rTMS DEVICE

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

Active rTMS

Sham rTMS DEVICE

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

Sham rTMS

Open Placebo 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.

Open Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Spaulding Rehabilitation Hospital: lead

Study Sites (1)

Spaulding Hospital Cambridge

Cambridge, Massachusetts, 02138, United States

RECRUITING

MeSH Terms

Conditions

Stroke; Paresis

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Felipe Fregni, MD, PhD, MPH

  Spaulding Rehabilitation Hospital/Harvard Medical School

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Felipe Fregni, MD, PhD, MPH

CONTACT

6179526156; fregni.felipe@mgh.harvard.edu

Elly Pichardo, MD

CONTACT

6179526154; epichardo@partners.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Spaulding Neuromodulation Center

Study Record Dates

• First Submitted: March 24, 2023
• First Posted: April 27, 2023
• Study Start: September 11, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: September 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)