Chronic Migraine, Medication Overuse Headache
Conditions
Keywords
Migraine, Non-Invasive Brain Stimulation, Medication Overuse Headache, Transcranial Magnetic Stimulation, rTMS
Brief summary
This randomized, double-blind, sham-controlled clinical trial aims to evaluate the efficacy of non-invasive brain stimulation as an add-on treatment to standard detoxification therapy in patients with chronic migraine and medication overuse. The study also seeks to identify sensory and biochemical biomarkers predictive of treatment response.
Detailed description
The main study is a randomized controlled trial enrolling patients with chronic migraine and medication overuse (MoH). Participants will undergo a standardized in-hospital detoxification protocol and will be randomly assigned to one of three parallel groups to receive either sham stimulation, active repetitive transcranial magnetic stimulation (rTMS) applied over the motor cortex face representation, or active rTMS applied over the motor cortex forearm representation. Stimulation will be delivered for five consecutive days. Clinical, sensory (Quantitative Sensory Testing, QST), and biochemical measures (plasma glutamate, serotonin, and calcitonin gene-related peptide, CGRP) will be collected at baseline and during follow-up.
Interventions
OTHERActive rTMS Motor Cortex Face
Participants will undergo a standardized in-hospital detoxification protocol for medication overuse and will receive high-frequency (10 Hz) active repetitive transcranial magnetic stimulation (rTMS) applied over the primary motor cortex corresponding to the face representation. Stimulation will be administered once daily for five consecutive days during hospitalization.
OTHERActive rTMS - Motor Cortex Forearm
Participants will undergo a standardized in-hospital detoxification protocol for medication overuse and will receive high-frequency (10 Hz) active repetitive transcranial magnetic stimulation (rTMS) applied over the primary motor cortex corresponding to the forearm representation. Stimulation will be administered once daily for five consecutive days during hospitalization.
OTHERSham rTMS
Participants will undergo a standardized in-hospital detoxification protocol for medication overuse and will receive sham high-frequency (10 Hz) repetitive transcranial magnetic stimulation (rTMS). Sham stimulation will be delivered using identical stimulation parameters and session duration as active rTMS, with the coil positioned to avoid effective cortical stimulation. Treatment will be administered once daily for five consecutive days during hospitalization.
Sponsors
IRCCS National Neurological Institute "C. Mondino" Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of chronic migraine and medication overuse according to ICHD-3 criteria * Ability to provide written informed consent
Exclusion criteria
* Major psychiatric disorders (e.g., major depressive disorder) * Changes in preventive migraine therapy within the last 3 months * Ongoing treatment with monoclonal antibodies for migraine prevention * Other significant neurological or systemic diseases * Pregnancy * Contraindications to transcranial magnetic stimulation (for main study participants)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of monthly days with moderate-to-severe headache | 1 month post-treatment | Change in the mean number of monthly days with moderate-to-severe headache during the month following treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants converting from chronic to episodic migraine | Up to 3 months post-treatment | Conversion from chronic to episodic migraine (\<15 headache days/month) assessed by headache diary |
| Change in monthly number of acute headache medication intakes | Up to 3 months post-treatment | Reduction in medication overuse assessed by patient diary |
| Acute headache medications | Up to 3 months post-treatment | Monthly consumption of acute headache medications |
| Number of participants initiating preventive migraine therapy | Up to 3 months post-treatment | Initiation of preventive migraine therapy during follow-up |
| Change in Quantitative Sensory Testing (QST) | Up to 3 months post-treatment | Changes in sensory and pain thresholds assessed by QST. QST is a panel of diagnostic tests used to assess somatosensory function. The panel of tests examine a broad range of different sensations, including hot, cold, touch, vibration. It has both positive and negative tests (can test for increased or reduced sensitivity). QST reflects a formalisation of existing neurological tests into a standardised battery designed to detect subtle changes in sensory function. |
| Change in plasma glutamate concentration | Up to 3 months post-treatment | Changes in plasma levels of glutamate |
| Change in plasma serotonin concentration | Up to 3 months post-treatment | Changes in plasma levels of serotonin |
| Change in plasma CGRP concentration | Up to 3 months post-treatment | Changes in plasma levels of CGRP |
Countries
Italy
Contacts
PRINCIPAL_INVESTIGATORGiuseppe Cosentino, MD
Translational Neurophysiology
Outcome results
None listed