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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
60
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.
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.
Translational Neurophysiology
Pavia, Italy
Number of monthly days with moderate-to-severe headache
Change in the mean number of monthly days with moderate-to-severe headache during the month following treatment
Time frame: 1 month post-treatment
Number of participants converting from chronic to episodic migraine
Conversion from chronic to episodic migraine (\<15 headache days/month) assessed by headache diary
Time frame: Up to 3 months post-treatment
Change in monthly number of acute headache medication intakes
Reduction in medication overuse assessed by patient diary
Time frame: Up to 3 months post-treatment
Acute headache medications
Monthly consumption of acute headache medications
Time frame: Up to 3 months post-treatment
Number of participants initiating preventive migraine therapy
Initiation of preventive migraine therapy during follow-up
Time frame: Up to 3 months post-treatment
Change in Quantitative Sensory Testing (QST)
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.
Time frame: Up to 3 months post-treatment
Change in plasma glutamate concentration
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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.
Changes in plasma levels of glutamate
Time frame: Up to 3 months post-treatment
Change in plasma serotonin concentration
Changes in plasma levels of serotonin
Time frame: Up to 3 months post-treatment
Change in plasma CGRP concentration
Changes in plasma levels of CGRP
Time frame: Up to 3 months post-treatment