Brain Stimulation for Fibromyalgia

Overseen By Alexandre Dasilva, DDs,DMedSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Michigan

Must not be taking: Opioids, Marijuana, Stimulants, others

Disqualifiers: Autoimmune diseases, Head injury, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 16

Duration: 2 weeks

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This project is being conducted to evaluate the impact of explosive synchronization (ES) and its treatment with non-invasive brain stimulation in fibromyalgia (FM). The study design has three components, however, only 2 aims are enrolling participants. The first part (Aim1) is a cross sectional assessment of brain network explosive synchronization activity, connectivity, and response to pain in healthy controls and age and sex-matched fibromyalgia patients; the third part (Aim 3) is a longitudinal assessment of fibromyalgia patients undergoing one week of sham followed by high-definition transcranial direct current stimulation (HD-tDCS) of the motor cortex (M1) or one week of ES HD-tDCS of a brain region identified from computer modelling (Aim 2).

Will I have to stop taking my current medications?

The trial requires that you do not use stimulant medications or routine daily use of opioid analgesics. You also cannot use over-the-counter pain medications on the day of certain tests or opioid painkillers 48 hours before some scans. Other medications may be allowed, but you should not start any new treatments for fibromyalgia during the study.

Is brain stimulation for fibromyalgia safe for humans?

Transcranial direct current stimulation (tDCS), including its high-definition version (HD-tDCS), is generally considered safe and well tolerated in humans, although more research is needed, especially at higher intensities and in older adults. ^{1 2 3 4 5}

How is HD-tDCS treatment different from other treatments for fibromyalgia?

HD-tDCS (High-Definition Transcranial Direct Current Stimulation) is unique because it uses a more focused electrical stimulation to modulate brain activity, specifically targeting the primary motor cortex, which can help reduce pain in fibromyalgia patients. Unlike traditional treatments, it is non-invasive and can provide immediate and lasting pain relief without medication. ^{1 6 7 8 9}

What data supports the effectiveness of this treatment for fibromyalgia?

Research shows that transcranial direct current stimulation (tDCS) can reduce pain in fibromyalgia patients. Studies found that active tDCS over specific brain areas significantly decreased pain scores and improved disability compared to sham treatments. ^{1 2 6 7 10}

Who Is on the Research Team?

Alexandre Dasilva, DDs,DMedsc

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for adults with fibromyalgia experiencing pain most days, and healthy right-handed controls with minimal pain. Participants must be able to visit the study site regularly and not start new treatments during the study. Exclusions include severe psychiatric illnesses, certain medical conditions like autoimmune diseases, knowledge of HD-tDCS that could bias results, or safety risks for brain stimulation or imaging.

Inclusion Criteria

My average pain level in the past week was 3 or more on a scale of 10.

I have been diagnosed with Fibromyalgia according to the 2011 criteria.

Healthy control participants must be capable of giving written informed consent

Exclusion Criteria

I do not use opioids or marijuana daily and have no history of substance abuse.

I will not take OTC pain meds on the day of my EEG/MRI.

I don't use opioids, marijuana daily, or have a history of substance abuse.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Run-in Observation

Participants undergo a run-in observational period with EEG, QST, and MRI assessments

Up to 33 days

3 visits (in-person)

Treatment

Participants receive two weeks of HD-tDCS or Sham treatment with 5 daily sessions per week

2 weeks

10 visits (in-person)

Follow-up

Participants are monitored for changes in brain connectivity and EEG metrics after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• HD-tDCS treatments
• Sham HD-tDCS treatments

Trial Overview The trial examines how a type of brain activity called explosive synchronization relates to chronic pain in fibromyalgia. It tests whether targeted non-invasive brain stimulation (HD-tDCS) can alter this activity and reduce pain. The study includes assessments using EEG and fMRI neuroimaging before and after sham or actual HD-tDCS treatment.

How Is the Trial Designed?

Group I: Aim 3- HD-tDCS of ES Experimental Treatment 4 Interventions

There will be two weeks of treatment in which participants will have 5 daily sessions of focused HD-tDCS or Sham per week.

Group II: Aim 3 - HD-tDCS of M1 Experimental Treatment 4 Interventions

There will be two weeks of treatment in which participants will have 5 daily sessions of focused HD-tDCS or Sham per week.

Group III: Aim 1 - Healthy control Experimental Treatment 2 Interventions

Participants will have three visits for this part along with a run-in observation period. An EEG with Quantitative Sensory Testing (QST) will be performed at visit 1 along with other measures. Additionally, the an MRI will be done at visit 2 along with other measures.

Group IV: Aim 1 - Fibromyalgia participant Experimental Treatment 2 Interventions

Participants will have three visits for this part along with a run-in observation period. An EEG with Quantitative Sensory Testing (QST) will be performed at visit 1 along with other measures. Additionally, the an MRI will be done at visit 2 along with other measures.

Group V: Aim 3 - Sham Placebo Group 4 Interventions

There will be two weeks of treatment in which participants will have 5 daily sessions of focused HD-tDCS or Sham per week.

HD-tDCS treatments is already approved in United States, European Union, Canada for the following indications:

Approved in United States as HD-tDCS for:

• Chronic pain
• Fibromyalgia
• Neuropathic pain

Approved in European Union as HD-tDCS for:

• Chronic pain
• Fibromyalgia
• Neuropathic pain

Approved in Canada as HD-tDCS for:

• Chronic pain
• Fibromyalgia
• Neuropathic pain

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

National Center for Complementary and Integrative Health (NCCIH)

Collaborator

Trials

886

Recruited

677,000+

Published Research Related to This Trial

In a randomized clinical trial involving 35 women with fibromyalgia, ten sessions of active transcranial direct current stimulation (tDCS) significantly reduced pain levels immediately after treatment and maintained these improvements for up to 90 days.

The active tDCS group also experienced enhancements in quality of life and reductions in fatigue, indicating that this non-invasive treatment could be a beneficial option for managing fibromyalgia symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Anodal Transcranial Direct Current Stimulation on the Primary Motor Cortex in Women With Fibromyalgia: A Randomized, Triple-Blind Clinical Trial. Loreti, EH., Freire, AM., Alexandre da Silva, A., et al.[2023]

Transcranial direct current stimulation (tDCS) targeting the primary motor cortex significantly reduced pain in fibromyalgia patients compared to sham stimulation, with effects lasting for at least 3 weeks after treatment.

The treatment was generally safe, with only mild adverse events reported, and cognitive function remained stable across all treatment groups, suggesting that tDCS could be a promising noninvasive option for managing fibromyalgia symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, sham-controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia. Fregni, F., Gimenes, R., Valle, AC., et al.[2022]

In a randomized controlled trial with 23 fibromyalgia patients, daily sessions of anodal transcranial direct current stimulation (tDCS) combined with multidisciplinary rehabilitation led to a significant reduction in pain perception as measured by the SF-36 pain domain.

While patients tolerated the tDCS treatment well without adverse effects, the overall improvements in quality of life and other pain measures were not statistically significant, suggesting that while tDCS may help with pain, its effectiveness in broader treatment contexts remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of transcranial direct current stimulation coupled with a multidisciplinary rehabilitation program for the treatment of fibromyalgia. Riberto, M., Marcon Alfieri, F., Monteiro de Benedetto Pacheco, K., et al.[2022]

Anodal transcranial direct current stimulation (tDCS) applied to the primary motor cortex significantly improved pain and overall function in patients with fibromyalgia, based on a meta-analysis of six randomized controlled trials involving 192 participants.

No significant adverse effects were reported, indicating that this treatment is safe, although it did not improve the pressure pain threshold compared to sham stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effiectiveness and safety of transcranial direct current stimulation in fibromyalgia: A systematic review and meta-analysis. Zhu, CE., Yu, B., Zhang, W., et al.[2022]

Home-based active transcranial direct current stimulation (a-tDCS) significantly reduced pain scores in patients with fibromyalgia, with a 36.53% reduction for the left dorsolateral prefrontal cortex (l-DLPFC) and 45.89% for the primary motor cortex (M1) compared to sham stimulation.

a-tDCS over M1 not only improved pain scores but also enhanced the function of the descending pain inhibitory system and increased the heat pain threshold, indicating its potential as an effective therapeutic approach for managing fibromyalgia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Home-Based Transcranial Direct Current Stimulation Over the Primary Motor Cortex and Dorsolateral Prefrontal Cortex in the Disability Due to Pain in Fibromyalgia: A Factorial Sham-Randomized Clinical Study. Caumo, W., Lopes Ramos, R., Vicuña Serrano, P., et al.[2023]

High-Definition transcranial Direct Current Stimulation (HD-tDCS) at amplitudes up to 4 mA was well tolerated by 292 older adults, with no safety-related adverse events reported and mostly mild sensations experienced during sessions.

The study demonstrated effective blinding for both participants and researchers, indicating that the sham stimulation was convincing, which supports the use of higher amplitudes for potentially greater therapeutic effects in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and blinding of high-definition transcranial direct current stimulation among older adults at intensities of up to 4 mA per electrode. El Jamal, C., Harrie, A., Rahman-Filipiak, A., et al.[2023]

Transcranial direct current stimulation (tDCS) significantly reduced pain levels in 46 Korean patients with fibromyalgia, showing improvements in visual analogue scale (VAS) pain scores after treatment, indicating its potential as an effective add-on therapy.

The treatment was safe, with no serious adverse events reported, and it also led to improvements in fatigue and depression scores, although it did not significantly affect anxiety or sleep quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of add-on transcranial direct current stimulation on pain in Korean patients with fibromyalgia. Kang, JH., Choi, SE., Park, DJ., et al.[2021]

High Definition transcranial direct current stimulation (HD-tDCS) is safe and well-tolerated in older adults, with no serious adverse events reported during a study involving 101 participants at stimulation intensities of 2 mA and 3 mA.

The study demonstrated effective blinding, as participants could not accurately distinguish between active and sham stimulation, indicating that HD-tDCS can be reliably used in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and blinding of 4x1 high-definition transcranial direct current stimulation (HD-tDCS) at two and three milliamps. Reckow, J., Rahman-Filipiak, A., Garcia, S., et al.[2020]

In a study involving 38 fibromyalgia patients, high-definition transcranial alternating current stimulation (HD-tACS) showed a significant reduction in the fibromyalgia impact questionnaire (FIQ) scores after two weeks, indicating potential benefits in managing symptoms.

Despite the positive findings, there were no significant differences in pain intensity compared to sham stimulation, and while most side effects were mild, one serious adverse event (a suicide attempt) raises safety concerns that need to be addressed in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using High-Definition Transcranial Alternating Current Stimulation to Treat Patients with Fibromyalgia: A Randomized Double-Blinded Controlled Study. Lin, AP., Chiu, CC., Chen, SC., et al.[2023]

In a study involving 18 fibromyalgia patients, both anodal and cathodal high-definition transcranial direct current stimulation (HD-tDCS) significantly reduced perceived pain compared to sham stimulation, showing immediate effects after cathodal stimulation and lasting effects for both types 30 minutes post-treatment.

The HD-tDCS technique was well tolerated by patients and also resulted in increased mechanical detection thresholds, indicating potential benefits beyond pain reduction, suggesting its usefulness in both research and clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focal modulation of the primary motor cortex in fibromyalgia using 4×1-ring high-definition transcranial direct current stimulation (HD-tDCS): immediate and delayed analgesic effects of cathodal and anodal stimulation. Villamar, MF., Wivatvongvana, P., Patumanond, J., et al.[2022]

Citations

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

Effects of Anodal Transcranial Direct Current Stimulation on the Primary Motor Cortex in Women With Fibromyalgia: A Randomized, Triple-Blind Clinical Trial. [2023]

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

A randomized, sham-controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia. [2022]

3. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Efficacy of transcranial direct current stimulation coupled with a multidisciplinary rehabilitation program for the treatment of fibromyalgia. [2022]

4. Sweden pubmed.ncbi.nlm.nih.gov

Effiectiveness and safety of transcranial direct current stimulation in fibromyalgia: A systematic review and meta-analysis. [2022]

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

Efficacy of Home-Based Transcranial Direct Current Stimulation Over the Primary Motor Cortex and Dorsolateral Prefrontal Cortex in the Disability Due to Pain in Fibromyalgia: A Factorial Sham-Randomized Clinical Study. [2023]

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

Tolerability and blinding of high-definition transcranial direct current stimulation among older adults at intensities of up to 4 mA per electrode. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Effects of add-on transcranial direct current stimulation on pain in Korean patients with fibromyalgia. [2021]

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

Tolerability and blinding of 4x1 high-definition transcranial direct current stimulation (HD-tDCS) at two and three milliamps. [2020]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Using High-Definition Transcranial Alternating Current Stimulation to Treat Patients with Fibromyalgia: A Randomized Double-Blinded Controlled Study. [2023]

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

Focal modulation of the primary motor cortex in fibromyalgia using 4×1-ring high-definition transcranial direct current stimulation (HD-tDCS): immediate and delayed analgesic effects of cathodal and anodal stimulation. [2022]