Clinical trial NCT06735768: Closed-loop RTMS for Short-term Migraine Prevention
Official title: Double-blind, Randomized, Sham-controlled Study of Closed-loop Repetitive Transcranial Magnet Stimulation (rTMS) for the Short-term Prevention of Migraine
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Migraine Disorders
Lead sponsor: Brightmind.AI
Sponsor class: INDUSTRY
Collaborators: name: Medical University of Vienna
First posted: 2024-12-16
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Migraine is a prevalent and debilitating primary headache disorder, where patients suffer from disabling symptoms that usually consist of a moderate to severe headache lasting 4 to 72 hours, nausea and/or vomiting, phonophobia and photophobia. Transcranial magnetic stimulation (TMS) is a noninvasive technique that is considered to be safe. Repetitive TMS (rTMS) might be useful for migraine prophylaxis. However, available studies on the use of rTMS for preventive treatment of migraine are limited. Currently, rTMS is not recommended in the recent guidelines for the treatment of migraine published by the German Neurological Society in 2022.

Therefore, the aim of the current study is to provide reliable data on the short-term effect of rTMS for the prevention of migraine. The investigators will follow the Guidelines of the International Headache Society for controlled trials of acute treatment of migraine attacks in adults: Fourth edition, with the exception of study duration, which will be limited to four weeks of baseline, three sessions of rTMS within a 10-day timeframe and 4 weeks of follow-up as our study aims to examine short-term efficacy.


Eligibility criteria: Inclusion criteria:

* Provision of signed and dated informed consent form
* Stated willingness to comply with all study procedures and availability for the duration of the study
* Male or female, aged 18-65
* Migraine without aura, migraine with aura or chronic migraine according to the diagnostic criteria of the third edition of the International Classification of Headache Disorders (ICHD-3) - Age of onset before 50 years of age
* At least 4 migraine days in each of three subsequent 4- week periods preceding the screening period. (Subsequently, the investigators use month synonymous for 4-week periods)
* At least 4 migraine days during one month of baseline prior to treatment.
* Ability to distinguish migraine headaches from other headache types (e.g., tension-type headaches)
* Willing to adhere to the rTMS regimen and able to monitor MD in Migraine diary
* No changes in medication usage/regime for three months before the start of treatment (incl. use of acute abortion / rescue medication). In case of Erenumab, Fremanezumab, Galcanezumab no changes in usage/regime for six months before the start of treatment. Every medication is reported and documented.
* No changes in medication usage/regime during the entire study period (i.e., keeping acute intervention protocol as previously handled for the past three months; not introducing new approaches in intervention/ prevention during this time period (such as anti-nausea drugs not previously taken)). Every medication is reported \& documented.
* Use of a single drug for migraine prophylaxis is permitted as long as the dosage has not been altered within 3 months of starting the study and the dosage must not be altered for the entire duration of the study.
* No other stimulation techniques.
* No change in acupuncture, relaxation training, biofeedback, behavioral therapy or other psychological or psychotherapeutic interventions for three months preceding the study and during the entire study period investigator.
* Ability to read and understand the written information (patient information, migraine diary, CRF and Adverse Events (AE) collecting form)
* Completed baseline headache diary with missing data on not more than 5 of 28 days.

Exclusion criteria:

* More than 26 headache days in any of three subsequent months preceding the screening visit.
* More than 26 headache days during baseline
* Pregnant persons
* Usage of Onabotulinumtoxin A for managing chronic migraines.
* Medication-overuse according to ICHD-3
* Presence of metals or implanted devices that can be in close proximity the of device (i.e., above the neckline) and can be adversely affected by magnetic fields including:

  * Stents
  * Implanted stimulators
  * Implanted vagus nerve or brain implants incl. deep brain stimulators
  * Implanted electrical devices
  * Cochlear implants for hearing
  * Any magnetic implants
  * Bullet fragments
  * Grenade fragments
* Presence of heart pacemakers, defibrillator, intracardiac lines or medication pumps
* Known severe adverse reactions in response to rTMS
* Patients diagnosed with bipolar disorder, substance use disorders or psychosis
* Patients with a known medical history, as well as a family history, of seizures.
* Patients experiencing chronic sleep deprivation
* Patients with structural CNS disorders such as a brain tumor, stroke, or traumatic brain injury.
* Patients with chronic tinnitus in the judgement of the investigator
* Patients with other disorders interfering with the study in the judgement of the investigator.
* Treatment with another investigational drug or other intervention until the end of the study
* Botulinum toxin-based infusions for cosmetic reasons at the forehead within a period of six months prior to study inclusion until the final visit.
* Other clinically relevant pain syndromes
* Depression or anxiety in the judgement of the investigator as assessed by means of BDI-II (score 20 or above) and DASS-21 (score 14 or above).
* Severe health risks in the judgement of the investigator. In particular this includes assessing the risk associated with a history of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.

Primary outcomes:
measure: Monthly migraine days (MMD)
timeFrame: comparing 4 weeks before with 4 weeks after rTMS
Secondary outcomes:
measure: 50 percent responder rate
timeFrame: comparing 4 weeks before with 4 weeks after rTMS
measure: Weekly Migraine days after stimulation.
timeFrame: comparing 4 weeks before with 4 weeks after rTMS
measure: Monthly headache days
timeFrame: comparing 4 weeks before with 4 weeks after rTMS
measure: Monthly (4 weeks) days with use of acute medication
timeFrame: comparing 4 weeks before with 4 weeks after rTMS
measure: Headache severity
timeFrame: comparing 4 weeks before with 4 weeks after rTMS
measure: Duration of migraine attacks
timeFrame: comparing 4 weeks before with 4 weeks after rTMS
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Univ.-Klinik für Neurologie, Medizinische Universität Wien
Study officials:
affiliation: Medical University Vienna
name: Christian Wöber, Prof., PhD
role: PRINCIPAL_INVESTIGATOR
References: