Brain Stimulation for Migraine

Overseen By Jacqueline Dobson, BA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Michigan

Must not be taking: Opioids, Dopaminergics, Ergotamines, others

Disqualifiers: Psychotic disorders, Neurological disorders, others

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

Compensation: Varies

Number of Visits: 23

Duration: 4 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether a type of brain stimulation called HD-tDCS (High-Definition Transcranial Direct Current Stimulation) can reduce migraine pain. Participants will be divided into groups to receive either real or "sham" (placebo-like) brain stimulation. Some participants with episodic migraines will also be observed without receiving any treatment. Individuals who have experienced migraines for at least six months with frequent headaches may be suitable candidates. Participants should be willing to avoid starting new treatments during the study. As an unphased trial, this study offers participants the chance to contribute to innovative research that could lead to new migraine treatments.

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

The trial does not specify if you must stop taking your current medications, but you should be willing to limit the introduction of new treatments and medications during the study period.

What prior data suggests that this brain stimulation technique is safe for migraine patients?

Research shows that transcranial direct current stimulation (tDCS) can safely treat migraines. Studies have found that most people tolerate tDCS well, with few reports of major side effects. Most side effects are minor, such as slight tingling or itching where the electrodes are placed. In trials, participants who received real tDCS experienced no serious safety issues compared to those who received a placebo treatment. This suggests that tDCS is a low-risk option for people with migraines. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about high-definition transcranial direct current stimulation (HD-tDCS) for migraines because it offers a non-invasive approach without the need for medication. Unlike standard treatments like triptans or preventive medications such as beta-blockers and antiepileptics, HD-tDCS uses targeted electrical currents to potentially relieve migraine symptoms. This method is unique because it can be applied bilaterally or unilaterally, offering flexibility in treatment based on patient needs. Additionally, the use of sham protocols in the study helps ensure that any improvements are due to the treatment itself, not placebo effects, which could pave the way for more precise and effective migraine therapies.

What evidence suggests that this trial's treatments could be effective for migraine?

Research has shown that high-definition transcranial direct current stimulation (HD-tDCS) can help reduce migraine pain. In this trial, participants will receive either active HD-tDCS treatment or a sham treatment. Studies have found that those who received active HD-tDCS experienced less migraine pain and improved daily functioning compared to those who received a sham treatment. One study discovered that using HD-tDCS for several weeks reduced the intensity and duration of migraines. Another study showed benefits for individuals with frequent migraines. These findings suggest that HD-tDCS could effectively ease migraine symptoms. ^{5 6 7 8 9}

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 aged 18-65 with episodic migraines that began before age 50. Participants should be willing to avoid new treatments during the study and not have a history of neurological disorders, major illnesses, psychiatric conditions, or substance abuse. Pregnant or breastfeeding individuals are excluded.

Inclusion Criteria

Willing to limit the introduction of new treatments and medications during the study period.

I started having migraines before I was 50 and now get them often.

Exclusion Criteria

I do not have any serious illnesses other than migraines.

My most severe pain is not in my head.

I do not have a severe mental health condition like major depression or schizophrenia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Baseline

Baseline visit with MRI and PET session

1 day

1 visit (in-person)

Treatment

Participants receive HD-tDCS brain stimulation treatments for 20 days

4 weeks

20 visits (in-person, M-F)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person) with MRI and PET session

What Are the Treatments Tested in This Trial?

Interventions

• HD-tDCS Active Protocol
• HD-tDCS Sham Protocol

Trial Overview The study tests if non-invasive brain stimulation can reduce migraine pain by administering it once daily for twenty days. Forty patients will receive either unilateral or bilateral treatment, while twenty will undergo a sham procedure without actual stimulation.

How Is the Trial Designed?

Group I: Active Bilateral Treatment Active Control 1 Intervention

Chronic migraine patients will be randomized (Taves method) to receive BILATERAL high-definition transcranial direct current stimulation (HD-tDCS\*) as 20 minute sessions, once daily for 20 days (M-F for 4 weeks).

Group II: No Treatment Active Control 1 Intervention

Episodic Migraine Patients will not receive study treatment. These patients will complete observational study components (Screening visit, baseline visit, MRI and PET scan only).

Group III: Active Unilateral Treatment Active Control 1 Intervention

Chronic migraine patients will be randomized (Taves method) to receive UNILATERAL high-definition transcranial direct current stimulation (HD-tDCS\*) as 20 minute sessions, once daily for 20 days (M-F for 4 weeks).

Group IV: Sham Treatment Placebo Group 1 Intervention

Chronic migraine patients will be randomized (Taves method) to receive SHAM high-definition transcranial direct current stimulation (HD-tDCS\*) as 30-second administrations at the beginning and end of each 20 minute session, once daily for 20 days (M-F for 4 weeks).

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

Transcranial direct current stimulation (tDCS) significantly reduced the number of monthly migraine days in patients with chronic migraine and medication overuse headache, showing better results compared to sham stimulation after 1 and 6 months.

EEG recordings indicated that tDCS increased alpha rhythm activity in the brain, suggesting it may enhance cortico-thalamic connections, which could be linked to the observed clinical improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anodal transcranial direct current stimulation in chronic migraine and medication overuse headache: A pilot double-blind randomized sham-controlled trial. De Icco, R., Putortì, A., De Paoli, I., et al.[2021]

Transcranial direct current stimulation (tDCS) is generally considered safe, with mild and transient adverse effects reported in clinical trials, but the frequency and relationship of these effects with clinical variables remain unclear due to selective reporting bias.

Out of 209 studies reviewed, 117 mentioned adverse effects, with common issues like itching and tingling reported more frequently in the active tDCS group, although these differences were not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. Brunoni, AR., Amadera, J., Berbel, B., et al.[2022]

Transcranial Direct Current Stimulation (tDCS) has been shown to be safe, with no reports of Serious Adverse Effects or irreversible injuries across over 33,200 sessions involving more than 1,000 subjects, including vulnerable populations.

Safety assessments indicate that the current densities used in conventional tDCS (≤4 milliamperes) are significantly lower than those that could potentially cause brain injury, suggesting that tDCS protocols are well within safe limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Bikson, M., Grossman, P., Thomas, C., et al.[2022]

Transcranial direct current stimulation (tDCS) applied over 4 weeks significantly reduces migraine pain intensity and duration, based on a meta-analysis of 5 randomized controlled trials involving 104 patients.

Both anodal and cathodal tDCS stimulation are effective in alleviating migraine pain, with benefits lasting for at least 4 weeks after treatment completion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review and Meta-Analysis on the Efficacy of Repeated Transcranial Direct Current Stimulation for Migraine. Cai, G., Xia, Z., Charvet, L., et al.[2022]

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]

Transcranial Direct Current Stimulation (tDCS) is generally considered safe, but there are concerns that it could lead to significant negative effects in healthy individuals.

The scientific community needs to be alerted about the potential risks of tDCS, emphasizing the importance of protecting healthy volunteers from possible harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcranial direct current stimulation in healthy participants. Boccard-Binet, S., Sen, A.[2021]

In a study involving 30 patients over 6 weeks, cathodal transcranial direct current stimulation (tDCS) significantly reduced the intensity of migraine pain and the duration of attacks compared to baseline, indicating its potential as a prophylactic therapy.

Compared to a sham stimulation group, only the intensity of pain was significantly reduced in the cathodal tDCS group, and importantly, no severe adverse effects were reported, highlighting the safety of this non-invasive treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cathodal transcranial direct current stimulation of the visual cortex in the prophylactic treatment of migraine. Antal, A., Kriener, N., Lang, N., et al.[2022]

Transcranial Direct Current Stimulation (tDCS) applied to the right primary motor cortex or sensory cortex significantly reduced migraine pain frequency, duration, and intensity in a study of 45 patients over 22 sessions across 10 weeks.

Both episodic and chronic migraine patients experienced significant improvements compared to a sham group, indicating that c-tDCS can be an effective prophylactic and therapeutic option for migraine treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of cathodal tDCS of the primary motor or sensory cortex in migraine: A randomized controlled trial. Rahimi, MD., Fadardi, JS., Saeidi, M., et al.[2020]

Anodal transcranial direct current stimulation (tDCS) over the visual cortex significantly reduced migraine frequency, duration, and medication intake in episodic migraine patients, demonstrating its potential as an effective preventive treatment.

The study showed that tDCS increased habituation to visual stimuli in both healthy volunteers and migraine patients, suggesting it can correct the low preactivation levels in the visual cortex associated with migraines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation (tDCS) of the visual cortex: a proof-of-concept study based on interictal electrophysiological abnormalities in migraine. Viganò, A., D'Elia, TS., Sava, SL., et al.[2021]

Microdermabrasion significantly reduced skin resistance by about 32%, allowing for higher doses of transcranial direct current stimulation (tDCS) without increasing skin sensations or device limitations.

The study found that while microdermabrasion increased perceived sensations slightly when not combined with sonication, overall, it enabled safer and more effective delivery of tDCS by lowering the voltage needed to achieve the same current.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microdermabrasion facilitates direct current stimulation by lowering skin resistance. Chhatbar, PY., Liu, S., Ramakrishnan, V., et al.[2023]

In a study involving 25 episodic migraine patients, high-definition transcranial direct current stimulation (HD-tDCS) over the primary motor cortex showed potential benefits for those with higher-frequency migraine attacks (more than 3 per month), improving clinical outcomes such as headache days and intensity.

The treatment was associated with increased availability of endogenous µ-opioid receptors, suggesting that the efficacy of HD-tDCS may be linked to enhanced pain modulation through these receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of High-Definition Transcranial Direct Current Stimulation on Headache Severity and Central µ-Opioid Receptor Availability in Episodic Migraine. DaSilva, AF., Kim, DJ., Lim, M., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37497372/

Effect of High-Definition Transcranial Direct Current ... Conclusion: The 10-daily M1 HD-tDCS can improve clinical outcomes in episodic migraineurs with a higher baseline frequency of migraine attacks ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1388245723002407

Efficacy of tDCS in chronic migraine: A multiprotocol ... This study investigated how high-definition transcranial direct current stimulation (HD-tDCS) over the primary motor cortex (M1) affects brain signal ...

3. frontiersin.org frontiersin.org/journals/pain-research/articles/10.3389/fpain.2024.1353987/full

Transcranial direct current stimulation for chronic ... Results: Significant improvements in both daily function and pain levels were observed in participants treated with active tDCS, compared to sham tDCS. Effects ...

4. mdpi.com mdpi.com/2076-3271/13/3/84

Transcranial Direct Current Stimulation in Episodic Migraine A random effect meta-analysis was conducted to evaluate the effects of cathodal and anodal tDCS on migraine frequency (days per month and attacks per month).

5. tandfonline.com tandfonline.com/doi/full/10.2147/JPR.S295704

A Systematic Review and Meta-Analysis on the Efficacy of ... tDCS treatment repeated over days for a period of 4 weeks or more is effective in reducing migraine pain intensity and duration of migraine episode.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9160451/

Transcranial direct current stimulation for migraine tDCS is a promising method for migraine treatment. In this study, we investigated the efficacy and safety of tDCS for migraine by conducting a systematic ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5007190/

Safety of transcranial Direct Current Stimulation: Evidence ... This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and ...

8. headachejournal.onlinelibrary.wiley.com headachejournal.onlinelibrary.wiley.com/doi/10.1111/head.14887

The safety and feasibility of transcranial direct current ... We found tDCS + ET was safe, feasible, and tolerable. Secondary outcomes suggested active tDCS + ET was superior to sham tDCS + ET when ...

9. epain.org epain.org/journal/view.html?uid=1917&vmd=Full

Effects of Transcranial Direct Current Stimulation on pain ... Conclusions: Our findings suggest that tDCS might be effective for fibromyalgia, migraine, and neuropathic pain associated with spinal cord ...