Mechanisms of Open and Hidden Placebo in Stroke Recovery

Mass General Brigham

Status: Enrolling

Conditions: Stroke; Hemiparesis

Treatments: Device: Sham rTMS; Device: Active rTMS; Dietary Supplement: Open Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05832567

2023P000884

Details and patient eligibility

About

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.

Full 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).

Enrollment: 56 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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56 participants in 4 patient groups, including a placebo group

Active rTMS

Active Comparator group

Description:

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.

Treatment:

Device: Active rTMS

Sham rTMS

Sham Comparator group

Description:

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.

Treatment:

Device: Sham rTMS

Open Placebo

Placebo Comparator group

Description:

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.

Treatment:

Dietary Supplement: Open Placebo

No Intervention

No Intervention group

Description:

It consists of treatment-as-usual group.