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

Trial Summary

What is the purpose of this trial?

This study investigates whether unilateral and bilateral non-invasive brain stimulation, given for 20 minutes/once per day for twenty days (M-F) can reduce migraine pain. Fourty patients will receive treatment (20 unilateral treatment, and 20 bilateral treatment), while twenty will receive a "sham" procedure. Another 20 Episodic Migraine patients will be recruited for the observational aim of the study which does not include brain stimulation.

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 data supports the effectiveness of the treatment HD-tDCS for migraine?

Research suggests that transcranial direct current stimulation (tDCS), including high-definition tDCS (HD-tDCS), may help reduce migraine pain and frequency. Some studies show it can improve headache severity and influence brain systems related to pain, although results are mixed and more research is needed to confirm its effectiveness. ^{1 2 3 4 5}

Is transcranial direct current stimulation (tDCS) safe for humans?

Transcranial direct current stimulation (tDCS) is generally considered safe, with mild side effects like itching, tingling, and headaches reported. Serious adverse effects have not been observed in human trials, even in potentially vulnerable groups like children and the elderly. ^{6 7 8 9 10}

How does brain stimulation differ from other migraine treatments?

Brain stimulation, specifically transcranial direct current stimulation (tDCS), is unique because it is a non-invasive technique that modulates brain activity by applying a small electrical current to specific areas of the brain, such as the motor or sensory cortex. Unlike traditional migraine medications, which often have low efficacy and tolerability, tDCS offers a novel approach by targeting the brain's cortical areas directly to reduce migraine frequency and intensity. ^{1 3 4 5 11}

Research Team

Alexandre Dasilva, DDs,DMedsc

Principal Investigator

University of Michigan

Eligibility Criteria

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

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

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

Exclusion Criteria

My most severe pain is not in my head.

I do not have any serious illnesses other than migraines.

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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) 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]

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) 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]

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]

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

A Systematic Review and Meta-Analysis on the Efficacy of Repeated Transcranial Direct Current Stimulation for Migraine. [2022]

2. New Zealand 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. [2023]

3. Netherlands 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. [2021]

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

Effectiveness of cathodal tDCS of the primary motor or sensory cortex in migraine: A randomized controlled trial. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Cathodal transcranial direct current stimulation of the visual cortex in the prophylactic treatment of migraine. [2022]

6. England pubmed.ncbi.nlm.nih.gov

A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. [2022]

7. 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]

8. England pubmed.ncbi.nlm.nih.gov

Microdermabrasion facilitates direct current stimulation by lowering skin resistance. [2023]

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

Safety of transcranial direct current stimulation in healthy participants. [2021]

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

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. [2022]

11. England 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. [2021]