Non-Invasive Brain Stimulation as Add-on Treatment in Chronic Migraine With Medication Overuse

February 26, 2026 updated by: IRCCS National Neurological Institute "C. Mondino" Foundation

Identification of Predictors of Treatment Response and Innovative Therapeutic Strategies Based on Non-Invasive Brain Stimulation in Patients With Chronic Migraine and Medication Overuse

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Pavia, Italy, 27100
        • Translational Neurophysiology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Active rTMS - Motor Cortex Face Representation
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.
Other: Active 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.
Experimental: Active rTMS - Motor Cortex Forearm Representation
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.
Other: Active 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.
Sham Comparator: Sham 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.
Other: Sham 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of monthly days with moderate-to-severe headache
Time Frame: 1 month post-treatment
Change in the mean number of monthly days with moderate-to-severe headache during the month following treatment
1 month post-treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants converting from chronic to episodic migraine
Time Frame: Up to 3 months post-treatment
Conversion from chronic to episodic migraine (<15 headache days/month) assessed by headache diary
Up to 3 months post-treatment
Change in monthly number of acute headache medication intakes
Time Frame: Up to 3 months post-treatment
Reduction in medication overuse assessed by patient diary
Up to 3 months post-treatment
Acute headache medications
Time Frame: Up to 3 months post-treatment
Monthly consumption of acute headache medications
Up to 3 months post-treatment
Number of participants initiating preventive migraine therapy
Time Frame: Up to 3 months post-treatment
Initiation of preventive migraine therapy during follow-up
Up to 3 months post-treatment
Change in Quantitative Sensory Testing (QST)
Time Frame: 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.
Up to 3 months post-treatment
Change in plasma glutamate concentration
Time Frame: Up to 3 months post-treatment
Changes in plasma levels of glutamate
Up to 3 months post-treatment
Change in plasma serotonin concentration
Time Frame: Up to 3 months post-treatment
Changes in plasma levels of serotonin
Up to 3 months post-treatment
Change in plasma CGRP concentration
Time Frame: Up to 3 months post-treatment
Changes in plasma levels of CGRP
Up to 3 months post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS National Neurological Institute "C. Mondino" Foundation

Investigators

  • Principal Investigator: Giuseppe Cosentino, MD, Translational Neurophysiology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 2, 2024

Primary Completion (Actual)

January 30, 2026

Study Completion (Actual)

January 30, 2026

Study Registration Dates

First Submitted

February 19, 2026

First Submitted That Met QC Criteria

February 26, 2026

First Posted (Actual)

March 2, 2026

Study Record Updates

Last Update Posted (Actual)

March 2, 2026

Last Update Submitted That Met QC Criteria

February 26, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • COSENTINO-MIGRAINE-TMS-2026

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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