Placebo Effects for Stroke Recovery

Recruiting in Palo Alto (17 mi)

Overseen by Felipe Fregni, MD, PhD, MPH

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Spaulding Rehabilitation Hospital

Disqualifiers: Prefrontal lesion, Unstable conditions, Pregnancy, others

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment rTMS for stroke recovery?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can help with motor recovery after a stroke, and placebo rTMS has also been found to have a positive effect on post-stroke motor rehabilitation. This suggests that both the actual treatment and the placebo can contribute to recovery, highlighting the importance of the placebo effect in this context. ^{1 2 3 4 5}

Is repetitive transcranial magnetic stimulation (rTMS) safe for humans?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is generally safe and well-tolerated in humans, with some studies specifically evaluating its safety in stroke patients. While some people may experience mild side effects like headaches or scalp discomfort, serious side effects are rare. ^{1 2 3 6 7}

How does the treatment Active rTMS differ from other treatments for stroke recovery?

Active rTMS (repetitive transcranial magnetic stimulation) is unique because it uses magnetic fields to stimulate nerve cells in the brain, which can help improve motor function after a stroke. Unlike traditional treatments, it involves non-invasive brain stimulation and can have significant placebo effects, which may enhance its therapeutic impact. ^{1 3 4 5 8}

Research Team

Felipe Fregni, MD, PhD, MPH

Principal Investigator

Spaulding Rehabilitation Hospital/Harvard Medical School

Eligibility Criteria

This trial is for adults over 18 who've had a stroke at least 6 months ago, resulting in one-sided weakness but still have some arm movement. They should not be severely disabled before the stroke and must understand instructions. People with joint pain, certain brain injuries from their stroke, pregnancy, unstable health conditions or electronic implants near the brain can't join.

Inclusion Criteria

I had a stroke more than 6 months ago.

You had difficulty with daily activities before the stroke.

Your upper arm and hand movement score on the Fugl-Meyer scale is between 11 and 56.

Exclusion Criteria

I had a stroke affecting the front part of my brain, confirmed by EEG.

Pregnancy

I have joint pain that could affect my ability to participate in assessments.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized into one of four groups: open placebo, sham rTMS, no intervention, or active rTMS, and undergo 2 weeks of daily intervention visits

2 weeks

10 sessions (in-person)

Follow-up

Participants are monitored for changes in motor function and brain activity after the treatment phase

2 weeks

Treatment Details

Interventions

• Active rTMS (Procedure)
• Open Placebo (Other)
• Sham rTMS (Procedure)

Trial Overview The study tests if different types of placebo (openly given as a placebo or disguised) and active repetitive Transcranial Magnetic Stimulation (rTMS), which is a non-invasive brain stimulation technique, affect recovery in chronic stroke patients differently.

Participant Groups

Group I: No Intervention Active Control 1 Intervention

It consists of treatment-as-usual group.

Group II: Active rTMS Active Control 1 Intervention

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 III: Sham rTMS Placebo Group 1 Intervention

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 IV: Open Placebo Placebo Group 1 Intervention

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Spaulding Hospital Cambridge Cambridge, MA

Who Is Running the Clinical Trial?

Spaulding Rehabilitation Hospital

Lead Sponsor

Trials

143

Patients Recruited

11,200+

Findings from Research

The new real electro-magnetic placebo (REMP) device effectively simulates the scalp sensations of real repetitive transcranial magnetic stimulation (rTMS) while ensuring that it does not produce any biologically active electric fields, making it a more reliable sham for clinical trials.

In tests, naive subjects were more likely to mistake the REMP-attenuated TMS for real rTMS compared to other sham methods, indicating that the REMP device provides a superior placebo experience, which is crucial for accurately assessing the efficacy of rTMS treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real electro-magnetic placebo (REMP) device for sham transcranial magnetic stimulation (TMS). Rossi, S., Ferro, M., Cincotta, M., et al.[2021]

Sham transcranial magnetic stimulation (TMS) is commonly used in research to differentiate real effects from side effects, but it has limitations in accurately controlling for placebo and sensory effects.

The authors argue that sham TMS cannot fully serve as a control condition because it does not adequately demonstrate the specificity of TMS effects, suggesting that it should be used alongside other control strategies in TMS studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rethinking the role of sham TMS. Duecker, F., Sack, AT.[2020]

In a meta-analysis of 93 randomized controlled trials involving repetitive transcranial magnetic stimulation (TMS), the overall incidence of adverse events (AEs) was found to be higher in the active TMS group (29.3%) compared to the placebo group (13.6%), indicating a 2.60 times greater risk of experiencing AEs with active treatment.

Despite the higher incidence of AEs, TMS is considered a safe and well-tolerated intervention, with common side effects including headache and dizziness, highlighting the importance of recognizing nocebo effects in both clinical trials and practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Nocebo Phenomena During Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis of Placebo-Controlled Clinical Trials. Zis, P., Shafique, F., Hadjivassiliou, M., et al.[2022]

The study found that healthy volunteers who believed they received an effective treatment (TENS) showed increased force output and enhanced excitability in the corticospinal system, indicating a placebo effect on motor performance.

Using transcranial magnetic stimulation (TMS), researchers demonstrated that this placebo effect was linked to cognitive factors, as the excitability changes occurred even when all subjects exerted the same force, suggesting a top-down influence on motor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo-induced changes in excitatory and inhibitory corticospinal circuits during motor performance. Fiorio, M., Emadi Andani, M., Marotta, A., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

A real electro-magnetic placebo (REMP) device for sham transcranial magnetic stimulation (TMS). [2021]

2. England pubmed.ncbi.nlm.nih.gov

Effectiveness of repetitive transcranial magnetic stimulation (rTMS) after acute stroke: A one-year longitudinal randomized trial. [2021]

3. Italy pubmed.ncbi.nlm.nih.gov

Placebo effect of rTMS on post-stroke motor rehabilitation: a meta-analysis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

On the importance of placebo timing in rTMS studies for pain relief. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Rethinking the role of sham TMS. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Nocebo Phenomena During Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis of Placebo-Controlled Clinical Trials. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

A sham-controlled trial of a 5-day course of repetitive transcranial magnetic stimulation of the unaffected hemisphere in stroke patients. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Placebo-induced changes in excitatory and inhibitory corticospinal circuits during motor performance. [2022]