Closed-loop RTMS for Short-term Migraine Prevention

Double-blind, Randomized, Sham-controlled Study of Closed-loop Repetitive Transcranial Magnet Stimulation (rTMS) for the Short-term Prevention of Migraine

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.

Study Overview

• Status: Recruiting
• Conditions: Migraine Disorders
• Intervention / Treatment: Device: rTMS treatment; Device: Determination of motor hotspot and motor treshold

• Study Type: Interventional
• Enrollment (Estimated): 88
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Luca Ticini, PhD; Phone Number: 0043019470414; Email: luca.ticini@brightmind.ai
• Study Contact Backup: Name: Gregor Kowarik, PhD; Phone Number: 0043019470414; Email: gregor.kowarik@brightmind.ai

Study Locations

• Austria
  • Vienna, Austria, 1010
    • Recruiting
    • Univ.-Klinik für Neurologie, Medizinische Universität Wien
    • Contact: Christian Wöber, Prof. PhD; Phone Number: 31170 +43140400; Email: christian.woeber@meduniwien.ac.at
    • Contact: Christian Wöber, Prof

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active group; This group receives rTMS treatment.	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
Sham Comparator: Sham group; This group receives sham treatment.	Device: Determination of motor hotspot and motor treshold; Determination of motor hotspot and motor treshold

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monthly migraine days (MMD)	Mean number of MMD 4 weeks before and 4 weeks after rTMS treatment.	comparing 4 weeks before with 4 weeks after rTMS

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
50 percent responder rate	Responder rate as a reduction in MMD by 50 percent or more.	comparing 4 weeks before with 4 weeks after rTMS
Weekly Migraine days after stimulation.	Mean	comparing 4 weeks before with 4 weeks after rTMS
Monthly headache days	Mean number of monthly headache days before and after rTMS treatment.	comparing 4 weeks before with 4 weeks after rTMS
Monthly (4 weeks) days with use of acute medication	Mean number of monthly days with acute medication usage before and after rTMS treatment.	comparing 4 weeks before with 4 weeks after rTMS
Headache severity	Mean headache severity of migraine headaches before and after rTMS treatment.	comparing 4 weeks before with 4 weeks after rTMS
Duration of migraine attacks	Mean duration of migraine attacks before and after rTMS treatment.	comparing 4 weeks before with 4 weeks after rTMS

Collaborators and Investigators

• Sponsor: Brightmind.AI
• Collaborators: Medical University of Vienna
• Investigators: Principal Investigator: Christian Wöber, Prof., PhD, Medical University Vienna

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: December 6, 2024
• First Submitted That Met QC Criteria: December 11, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: 2145/2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No