Mechanisms of Open and Hidden Placebo in Stroke Recovery

December 15, 2023 updated by: Felipe Fregni, MD, PhD, MPH, Spaulding Rehabilitation Hospital
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.

Study Overview

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 Type

Interventional

Enrollment (Estimated)

56

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • Massachusetts
      • Cambridge, Massachusetts, United States, 02138
        • Recruiting
        • Spaulding Hospital Cambridge
        • Contact:
        • Principal Investigator:
          • Felipe Fregni, MD, PhD, MPH

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
Subjects will undergo repetitive transcranial magnetic stimulation, each session lasting 20 minutes.
Sham Comparator: 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.
Subjects will undergo sham repetitive transcranial magnetic stimulation, each session lasting 20 minutes.
Placebo Comparator: 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.
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: No Intervention
It consists of treatment-as-usual group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Change from 2 weeks to baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fugl-Meyer motor scale (FM)
Time Frame: Change from 2 weeks to baseline
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.
Change from 2 weeks to baseline
Premotor-M1 (PM-M1) connectivity
Time Frame: Change from 2 weeks to baseline
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.
Change from 2 weeks to baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Felipe Fregni, MD, PhD, MPH, Spaulding Rehabilitation Hospital/Harvard Medical School

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2023

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

June 30, 2025

Study Registration Dates

First Submitted

March 24, 2023

First Submitted That Met QC Criteria

April 24, 2023

First Posted (Actual)

April 27, 2023

Study Record Updates

Last Update Posted (Estimated)

December 21, 2023

Last Update Submitted That Met QC Criteria

December 15, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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