Individualized Location-based rTMS for Migraine Treatment: A Multicenter Clinical Study (individua rTMS)

July 18, 2025 updated by: First Affiliated Hospital of Zhejiang University

Efficacy of Individualized Location-based Repetitive Transcranial Magnetic Stimulation in the Treatment of Migraine: a Prospective Clinical Study

For migraine patients experiencing at least four attack days per month and undergoing transcranial magnetic stimulation (TMS) treatment, a randomized, double-blind controlled trial is conducted, dividing participants into a traditional targeting group and an individualized targeting group. Patients in both groups are followed up before treatment and at 1, 2, and 3 months post-treatment, evaluating the following parameters: migraine diaries, the number of migraine days, rescue medication usage, headache intensity, the number of moderate-to-severe migraine days, and the proportion of patients achieving a ≥50% reduction in migraine days. Further assessments include changes in the Migraine Disability Assessment (MIDAS), Headache Impact Test-6 (HIT-6), Migraine-Specific Quality of Life Questionnaire (MSQ), Pittsburgh Sleep Quality Index (PSQI), Patient Global Impression of Change (PGIC), 24-item Hamilton Depression Scale (HAMD-24), and 14-item Hamilton Anxiety Scale (HAMA-14). Biomarker and metabolic analyses include tryptophan and kynurenine metabolism, calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), substance P, endothelin-1, inflammatory cytokines (IL-1β, IL-6, TNF-α, TGF-β1), glutamate, endocannabinoids and related lipids, as well as gut microbiota composition. Additionally, changes in resting-state functional magnetic resonance imaging (rs-fMRI) before and after treatment are analyzed. This study aims to compare the efficacy of TMS treatment under different targeting strategies in migraine patients, providing theoretical support for clinical applications.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
152

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China
        • The First Affiliated Hospital, Zhejiang University School of Medicine
        • Contact:

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Aged between 18 and 65 years; both men and women.
  • Diagnosis of migraine according to the International Classification of Headache Disorders, 3rd edition (ICHD-III), with first onset before age 50 and a history of migraine for more than 1 year.
  • Migraine frequency of ≥4 days per month during both the 3 months prior to the screening period and the screening period itself.
  • Informed consent documents are signed, and subjects are cooperative with the evaluation and rTMS treatment, having been informed of known and potential risks and available alternative treatments.

Exclusion Criteria:

  • Patients with contraindications to TMS (e.g., metal implants, pacemakers).
  • Severe anxiety or depression (HAMD score >35, HAMA score >29).
  • History of migraine prophylactic drug adjustment during the screening and treatment period.
  • Aphasia or cognitive dysfunction (MMSE score ≤23).
  • Pregnancy or lactation.
  • Clinicians assess severe comorbidities that are not treatable.

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: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Individualized location-based Repetitive Transcranial Magnetic Stimulation
Enhancing targeting accuracy through personalized target localization to improve the analgesic response rate of rTMS.
Device: Individualized location-based Repetitive Transcranial Magnetic Stimulation
Enhancing targeting accuracy through personalized target localization to improve the analgesic response rate of rTMS.
Active Comparator: Traditional location-based Repetitive Transcranial Magnetic Stimulation
Recent studies have shown that the dorsolateral prefrontal cortex (DLPFC) plays an inhibitory role in the human pain pathway. High-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the left DLPFC has been found to improve chronic migraine.
Device: Traditional location-based Repetitive Transcranial Magnetic Stimulation
Recent studies have shown that the dorsolateral prefrontal cortex (DLPFC) plays an inhibitory role in the human pain pathway. High-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the left DLPFC has been found to improve chronic migraine.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in the monthly average number of migraine days
Time Frame: from baseline to 1 month after treatment completion.
A migraine day: any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache: a migraine with or without aura, lasting for ≥30 minutes, and meeting at least 1 of the following criteria (a and/or b): a) ≥2 of the following: unilateral location, pulsating quality, moderate to severe pain intensity, aggravation by or causing avoidance of routine physical activity; b) ≥1 of the following: nausea and/or vomiting, photophobia, and phonophobia. If the participant took a migraine-specific medication during aura or to treat headache on a calendar day, it was counted as a migraine day regardless of the duration and pain features/associated symptoms.
from baseline to 1 month after treatment completion.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in the monthly average number of migraine days
Time Frame: from baseline to 2.3 month after treatment completion.
A migraine day was any calendar day in which the participant experienced a qualified migraine headache (as previously described). If the participant took a migraine-specific medication during aura or to treat headache on a calendar day, it was counted as a migraine day regardless of the duration and pain features/associated symptoms. A moderate or severe migraine day was a migraine day of moderate or severe pain intensity. Months were defined as 28-day intervals.
from baseline to 2.3 month after treatment completion.
Mean Change From Baseline in the Migraine Disability Assessment (MIDAS) Total Score
Time Frame: Compared to baseline 3 months after treatment completion.
The Migraine Disability Assessment (MIDAS) is a retrospective, self-administered, 5-item questionnaire that measures headache-related disability as lost time due to headache from paid work or school, household work, and non-work activities. Participants provide the number of missed work or school days; missed household chores days; missed social or leisure activity days; and days at work or school, and separately at home, where productivity was reduced by half or more in the last 3 months (scale: 0 - 90 for each of 5 subscales). The 5 subscale scores are summed to compute the MIDAS total score (scale: 0 - 450). Lower scores indicate less headache-related disability.
Compared to baseline 3 months after treatment completion.
Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ)
Time Frame: from baseline to 1.2.3 month after treatment completion.
The Migraine Specific Quality of Life (MSQoL) is a self-administered, 14-item instrument that has been validated in 3 domains: role restriction, role prevention, and the emotional function. The role function-restrictive domain consists of 7 items that describe how migraine limits one's daily social and work-related activities. Participants respond to items using a 6-point scale: "none of the time," "a little bit of the time," "some of the time," "a good bit of the time," "most of the time," and "all of the time," which are assigned scores of 1 to 6, respectively. Item scores are recoded using (7 - original score). Next, raw dimension scores are computed as a sum of recoded item scores and rescaled from a 0 to 100 scale such that higher scores indicate better quality of life.
from baseline to 1.2.3 month after treatment completion.
Mean Change From Baseline in the Headache Impact Test-6 (HIT-6 )
Time Frame: from baseline to 1.2.3 month after treatment completion.
HIT-6 (Headache Impact Test-6) for Migraine: The HIT-6 is a widely used tool to assess the impact of headaches on a patient's quality of life. It consists of 6 questions, each rated on a 5-point scale ranging from "Never" to "Always." The total score is obtained by summing the individual item scores, with a higher score indicating a greater impact of migraine on the patient's daily functioning. A decrease in the HIT-6 score from baseline indicates an improvement in the patient's condition and a reduction in the impact of migraines on their life.
from baseline to 1.2.3 month after treatment completion.
Mean Change From Baseline in the Pittsburgh Sleep Quality Index(PSQI )
Time Frame: from baseline to 1.2.3 month after treatment completion.
PSQI (Pittsburgh Sleep Quality Index) for Sleep: The PSQI is a validated questionnaire used to assess the quality and patterns of sleep in the past month. It includes 19 items across 7 component areas: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction. Each component is scored on a 0 to 3 scale, and the total score ranges from 0 to 21, with higher scores indicating poorer sleep quality. A decrease in the PSQI score from baseline indicates an improvement in sleep quality.
from baseline to 1.2.3 month after treatment completion.
Mean Change From Baseline in the Patient Global Impression of Change(PGIC )
Time Frame: from baseline to 3 month after treatment completion.

PGIC (Patient Global Impression of Change): The PGIC is a single-item scale used to assess the patient's overall perception of change in their condition over time. The patient rates their perceived change in symptoms or overall health since the start of the study or treatment on a 7-point scale, where:

  1. = Very Much Improved
  2. = Much Improved
  3. = Minimally Improved
  4. = No Change
  5. = Minimally Worse
  6. = Much Worse
  7. = Very Much Worse

A higher score indicates a negative change in the patient's condition, while a lower score indicates improvement. The mean change from baseline reflects the overall perceived improvement or worsening of the patient's condition during the study period.
from baseline to 3 month after treatment completion.
Mean Change From Baseline in the HAMD-24 (Hamilton Depression Rating Scale, 24-item).
Time Frame: from baseline to 1.2.3 month after treatment completion.
HAMD-24 (Hamilton Depression Rating Scale, 24-item): The HAMD-24 is a clinician-administered scale used to assess the severity of depressive symptoms. It consists of 24 items, with each item scored on a 3 to 5-point scale based on the severity of the symptom (e.g., 0 = not present, 1 = mild, 2 = moderate, 3 = severe). The total score is calculated by summing the individual item scores, with higher scores indicating more severe depression. A reduction in the HAMD-24 score from baseline indicates improvement in the severity of depressive symptoms.
from baseline to 1.2.3 month after treatment completion.
Mean Change From Baseline in the HAMA-14 (Hamilton Anxiety Rating Scale, 14-item).
Time Frame: from baseline to 1.2.3 month after treatment completion.
HAMA-14 (Hamilton Anxiety Rating Scale, 14-item): The HAMA-14 is a clinician-administered scale used to assess the severity of anxiety symptoms. It includes 14 items that cover both psychic and somatic aspects of anxiety, such as tension, fear, insomnia, and somatic symptoms (e.g., gastrointestinal distress, dizziness). Each item is rated on a 5-point scale ranging from 0 (not present) to 4 (severe). The total score is calculated by summing the individual item scores, with higher scores indicating greater severity of anxiety. A reduction in the HAMA-14 score from baseline indicates a decrease in anxiety symptoms.
from baseline to 1.2.3 month after treatment completion.
Metabolomics (Tryptophan and Kynurenine)
Time Frame: Treatment completion (2 weeks) vs. baseline.

Tryptophan and Kynurenine:

Measurement Method: Liquid Chromatography-Mass Spectrometry (LC-MS) or High-Performance Liquid Chromatography (HPLC) with UV detection.

Units: µmol/L or nmol/mL.
Treatment completion (2 weeks) vs. baseline.
Mean Change From Baseline in Inflammatory Biomarker Levels.
Time Frame: Treatment completion (2 weeks) vs. baseline.

CGRP (Calcitonin Gene-Related Peptide), PACAP (Pituitary Adenylate Cyclase-Activating Polypeptide), VIP (Vasoactive Intestinal Peptide), NPY (Neuropeptide Y), Substance P, Endothelin-1:

Measurement Method: Enzyme-Linked Immunosorbent Assay (ELISA), Radioimmunoassay (RIA), or Luminex xMAP technology.

Units: pg/mL or ng/mL.

Inflammatory Factors (IL-1β, IL-6, TNF-α, TGF-β1):

Measurement Method: ELISA. Units: pg/mL or ng/mL.
Treatment completion (2 weeks) vs. baseline.
Mean Change From Baseline in Glutamate, Endocannabinoids and Related Lipids
Time Frame: Treatment completion (2 weeks) vs. baseline.

Glutamate:

Measurement Method:High-Performance Liquid Chromatography (HPLC) with fluorescence detection or LC-MS/MS.

Units:µmol/L or nmol/mL.

Endocannabinoids:

Measurement Method:Liquid Chromatography-Mass Spectrometry (LC-MS) or Gas Chromatography-Mass Spectrometry (GC-MS).

Units: pg/mL or nmol/L.

Related Lipids:

Measurement Method: LC-MS/MS or Gas Chromatography-Mass Spectrometry (GC-MS). Units:ng/mL or µg/mL.
Treatment completion (2 weeks) vs. baseline.
Mean Change From Baseline in Gut Microbiota Composition
Time Frame: Treatment completion (2 weeks) vs. baseline.

Gut Microbiota:

Measurement Method: 16S rRNA Gene Sequencing (Next-Generation Sequencing, NGS) or Metagenomic Sequencing.

Units: Relative abundance (percentage of total microbiota composition) or Operational Taxonomic Unit (OTU) counts.
Treatment completion (2 weeks) vs. baseline.
Changes in pain-related brain regions and connectivity in resting-state functional magnetic resonance imaging (rs-fMRI)
Time Frame: Treatment completion (2 weeks) vs. baseline.

Resting-State fMRI (rs-fMRI): This imaging technique assesses brain activity in the absence of an explicit task. It measures spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signal, which is an indicator of neural activity.

Analysis Focus:The primary focus is on pain-related brain regions such as the somatosensory cortex, anterior cingulate cortex (ACC), insula, thalamus, and prefrontal cortex , as well as changes in the functional connectivity between these regions.

Connectivity Analysis:Functional connectivity will be evaluated by examining seed-based analysis or independent component analysis (ICA) to identify altered networks related to pain processing and perception.
Treatment completion (2 weeks) vs. baseline.

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
First Affiliated Hospital of Zhejiang University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Red Cross Hospital, Hangzhou, China
The Third Affiliated hospital of Zhejiang Chinese Medical University
The Affiliated Hospital of Hangzhou Normal University

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 (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 25, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 25, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 25, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 17, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 18, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 25, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 18, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • [2025C]IIT. No. 013

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Time Frame

mar-15-2025. jun-15-2027

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

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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