Closed-loop RTMS for Short-term Migraine Prevention

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.