Mechanisms of Open and Hidden Placebo in Stroke Recovery

Stroke Clinical Trial

Official title:

Mechanisms of Open and Hidden Placebo in Stroke Recovery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05832567
• Other study ID #: 2023P000884
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2023
• Est. completion date: June 30, 2025

Study information

• Verified date: December 2023
• Source: Spaulding Rehabilitation Hospital
• Contact: Felipe Fregni, MD, PhD, MPH
• Phone: 6179526156
• Email: fregni.felipe[@]mgh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 56
• Est. completion date: June 30, 2025
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hemiparesis
• Paresis
• Stroke

Intervention

Device:
• Active rTMS
Subjects will undergo repetitive transcranial magnetic stimulation, each session lasting 20 minutes.
• Sham rTMS
Subjects will undergo sham repetitive transcranial magnetic stimulation, each session lasting 20 minutes.

Dietary Supplement:
• 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.

Locations

Country	Name	City	State
United States	Spaulding Hospital Cambridge	Cambridge	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Spaulding Rehabilitation Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Change from 2 weeks to baseline
Secondary	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.	Change from 2 weeks to baseline