NCT07442916

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Jan 2024

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 2, 2024

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 30, 2026

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 30, 2026

Completed
20 days until next milestone

First Submitted

Initial submission to the registry

February 19, 2026

Completed
11 days until next milestone

First Posted

Study publicly available on registry

March 2, 2026

Completed
Last Updated

March 2, 2026

Status Verified

February 1, 2026

Enrollment Period

2.1 years

First QC Date

February 19, 2026

Last Update Submit

February 26, 2026

Conditions

Chronic MigraineMedication Overuse Headache

Keywords

MigraineNon-Invasive Brain StimulationMedication Overuse HeadacheTranscranial Magnetic StimulationrTMS

Outcome Measures

Primary Outcomes (1)

  • 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

    1 month post-treatment

Secondary Outcomes (8)

  • Number of participants converting from chronic to episodic migraine

    Up to 3 months post-treatment

  • Change in monthly number of acute headache medication intakes

    Up to 3 months post-treatment

  • Acute headache medications

    Up to 3 months post-treatment

  • Number of participants initiating preventive migraine therapy

    Up to 3 months post-treatment

  • Change in Quantitative Sensory Testing (QST)

    Up to 3 months post-treatment

  • +3 more secondary outcomes

Study Arms (3)

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.

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.

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.

Other: Sham rTMS

Interventions

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 Face Representation
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.

Active rTMS - Motor Cortex Forearm Representation
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.

Sham rTMS

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosis of chronic migraine and medication overuse according to ICHD-3 criteria
  • Ability to provide written informed consent

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Translational Neurophysiology

Pavia, 27100, Italy

Location

Related Publications (3)

  • 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.

    PMID: 15546593BACKGROUND

  • Knotkova 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.

    PMID: 34062145BACKGROUND

  • Rossi 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.

    PMID: 19833552BACKGROUND

MeSH Terms

Conditions

Headache Disorders, SecondaryMigraine Disorders

Condition Hierarchy (Ancestors)

Headache DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesHeadache Disorders, Primary

Study Officials

  • Giuseppe Cosentino, MD

    Translational Neurophysiology

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 19, 2026

First Posted

March 2, 2026

Study Start

January 2, 2024

Primary Completion

January 30, 2026

Study Completion

January 30, 2026

Last Updated

March 2, 2026

Record last verified: 2026-02

Data Sharing

IPD Sharing
Will not share

Locations

IT(1)