Chronic MigraineNCT07442916
Non-Invasive Brain Stimulation as Add-on Treatment in Chronic Migraine With Medication Overuse
A study testing Active rTMS Motor Cortex Face and Active rTMS - Motor Cortex Forearm in people with Chronic Migraine and Medication Overuse Headache, run by IRCCS National Neurological Institute "C. Mondino" Foundation at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Chronic Migraine, Medication Overuse Headache
- What is being tested?
- Active rTMS Motor Cortex Face and Active rTMS - Motor Cortex Forearm
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteItaly
- Study dates
- 2 Jan 2024to 30 Jan 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of chronic migraine and medication overuse according to ICHD-3 criteria
- Ability to provide written informed consent
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Chronic Migraine, Medication Overuse Headache
- Being tested
- Active rTMS Motor Cortex Face, Active rTMS - Motor Cortex Forearm, Sham rTMS
- Keywords
- Migraine, Non-Invasive Brain Stimulation, Medication Overuse Headache, Transcranial Magnetic Stimulation, rTMS
- Medical subject headings
- Headache Disorders, Secondary, Migraine Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active rTMS Motor Cortex FaceOther
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.
Active rTMS - Motor Cortex ForearmOther
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 rTMSOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Active rTMS - Motor Cortex Face Representation | Experimental | 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. Receives: Other: Active rTMS Motor Cortex Face |
| Active rTMS - Motor Cortex Forearm Representation | Experimental | 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. Receives: Other: Active rTMS - Motor Cortex Forearm |
| Sham rTMS | Sham comparator | 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. Receives: Other: Sham rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 1 month post-treatment
Secondary outcomes (8)
Number of participants converting from chronic to episodic migraine
Conversion from chronic to episodic migraine (<15 headache days/month) assessed by headache diary
Measured: Up to 3 months post-treatment
Change in monthly number of acute headache medication intakes
Reduction in medication overuse assessed by patient diary
Measured: Up to 3 months post-treatment
Acute headache medications
Monthly consumption of acute headache medications
Measured: Up to 3 months post-treatment
Number of participants initiating preventive migraine therapy
Initiation of preventive migraine therapy during follow-up
Measured: 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.
Measured: Up to 3 months post-treatment
Change in plasma glutamate concentration
Changes in plasma levels of glutamate
Measured: Up to 3 months post-treatment
Change in plasma serotonin concentration
Changes in plasma levels of serotonin
Measured: Up to 3 months post-treatment
Change in plasma CGRP concentration
Changes in plasma levels of CGRP
Measured: Up to 3 months post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2026
- Study start2 Jan 2024
- Primary completion30 Jan 2026
- Study completion30 Jan 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Chronic MigraineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS National Neurological Institute "C. Mondino" Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Giuseppe Cosentino, MD, Principal investigator, Translational Neurophysiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07442916
- Sponsor's protocol ID
- COSENTINO-MIGRAINE-TMS-2026
- Status last verified
- Feb 2026
- First submitted
- 19 Feb 2026
- Last updated
- 2 Mar 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Brighina F, Piazza A, Vitello G, Aloisio A, Palermo A, Daniele O, Fierro B. rTMS of the prefrontal cortex in the treatment of chronic migraine: a pilot study. J Neurol Sci. 2004 Dec 15;227(1):67-71. doi: 10.1016/j.jns.2004.08.008.
PubMed 15546593Knotkova H, Hamani C, Sivanesan E, Le Beuffe MFE, Moon JY, Cohen SP, Huntoon MA. Neuromodulation for chronic pain. Lancet. 2021 May 29;397(10289):2111-2124. doi: 10.1016/S0140-6736(21)00794-7.
PubMed 34062145Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.
PubMed 19833552
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of Predictors of Treatment Response and Innovative Therapeutic Strategies Based on Non-Invasive Brain Stimulation in Patients With Chronic Migraine and Medication Overuse
- ClinicalTrials.gov ID
- NCT07442916
- Acronym / sponsor ID
- COSENTINO-MIGRAINE-TMS-2026
- Conditions
- Chronic Migraine, Medication Overuse Headache
- Keywords
- Migraine, Non-Invasive Brain Stimulation, Medication Overuse Headache, Transcranial Magnetic Stimulation, rTMS
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- IRCCS National Neurological Institute "C. Mondino" FoundationUniversity, hospital or other
- Study start
- 2 Jan 2024 (actual)
- Primary completion
- 30 Jan 2026 (actual)
- Study completion
- 30 Jan 2026 (actual)
- First posted
- 2 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Active rTMS - Motor Cortex Face Representation | Experimental | Other: Active rTMS Motor Cortex FaceParticipants 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. |
| Active rTMS - Motor Cortex Forearm Representation | Experimental | Other: Active rTMS - Motor Cortex ForearmParticipants 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 rTMS | Sham comparator | Other: Sham rTMSParticipants 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Diagnosis of chronic migraine and medication overuse according to ICHD-3 criteria
- Ability to provide written informed consent
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active rTMS Motor Cortex FaceParticipants 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 Representation |
| Active rTMS - Motor Cortex ForearmParticipants 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 Representation |
| Sham rTMSParticipants 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 |
Primary outcome
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
8 secondary outcomes
Number of participants converting from chronic to episodic migraine
Time frame: Up to 3 months post-treatment
Change in monthly number of acute headache medication intakes
Time frame: Up to 3 months post-treatment
Acute headache medications
Time frame: Up to 3 months post-treatment
Number of participants initiating preventive migraine therapy
Time frame: Up to 3 months post-treatment
Change in Quantitative Sensory Testing (QST)
Time frame: Up to 3 months post-treatment
Change in plasma glutamate concentration
Time frame: Up to 3 months post-treatment
Change in plasma serotonin concentration
Time frame: Up to 3 months post-treatment
Change in plasma CGRP concentration
Time frame: Up to 3 months post-treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2026.
- Background: PubMed 15546593Brighina F, Piazza A, Vitello G, Aloisio A, Palermo A, Daniele O, Fierro B. rTMS of the prefrontal cortex in the treatment of chronic migraine: a pilot study. J Neurol Sci. 2004 Dec 15;227(1):67-71. doi: 10.1016/j.jns.2004.08.008.
- Background: PubMed 34062145Knotkova H, Hamani C, Sivanesan E, Le Beuffe MFE, Moon JY, Cohen SP, Huntoon MA. Neuromodulation for chronic pain. Lancet. 2021 May 29;397(10289):2111-2124. doi: 10.1016/S0140-6736(21)00794-7.
- Background: PubMed 19833552Rossi S, Hallett M, Rossini PM, Pascual-Leone A; Safety of TMS Consensus Group. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol. 2009 Dec;120(12):2008-2039. doi: 10.1016/j.clinph.2009.08.016. Epub 2009 Oct 14.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Giuseppe Cosentino, MD principal investigator
Translational Neurophysiology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active rTMS Motor Cortex Face and Active rTMS - Motor Cortex Forearm in people with Chronic Migraine and Medication Overuse Headache, run by IRCCS National Neurological Institute "C. Mondino" Foundation at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of monthly days with moderate-to-severe headache (time frame: 1 month post-treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07442916, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2026.