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

Overview

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.

Interventions

• Device rTMS treatment
  Brightmind.AI´s rTMS protocol is applied
• Device Determination of motor hotspot and motor treshold
  Determination of motor hotspot and motor treshold

Primary outcome measures

• Monthly migraine days (MMD) [Time frame: comparing 4 weeks before with 4 weeks after rTMS]

Secondary outcome measures (6)

• 50 percent responder rate [Time frame: comparing 4 weeks before with 4 weeks after rTMS]
• Weekly Migraine days after stimulation. [Time frame: comparing 4 weeks before with 4 weeks after rTMS]
• Monthly headache days [Time frame: comparing 4 weeks before with 4 weeks after rTMS]
• Monthly (4 weeks) days with use of acute medication [Time frame: comparing 4 weeks before with 4 weeks after rTMS]
• Headache severity [Time frame: comparing 4 weeks before with 4 weeks after rTMS]
• Duration of migraine attacks [Time frame: comparing 4 weeks before with 4 weeks after rTMS]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Prevention

Study locations

Austria · 1 center

• Univ.-Klinik für Neurologie, Medizinische Universität Wien — Vienna

Identifiers

NCT: NCT06735768 · 2145/2023

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗