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

N/ANot Yet RecruitingNCT07086274

First Affiliated Hospital of Zhejiang University152 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

152

Interventions

Individualized location-based Repetitive Transcranial Magnetic StimulationDEVICE

Enhancing targeting accuracy through personalized target localization to improve the analgesic response rate of rTMS.

Traditional location-based Repetitive Transcranial Magnetic StimulationDEVICE

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Change in the monthly average number of migraine days

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.

Time frame: from baseline to 1 month after treatment completion.

Secondary Outcomes

Change in the monthly average number of migraine days

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.

Time frame: from baseline to 2.3 month after treatment completion.

Mean Change From Baseline in the Migraine Disability Assessment (MIDAS) Total Score

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.

Time frame: Compared to baseline 3 months after treatment completion.

Mean Change From Baseline in the Migraine-Specific Quality of Life Questionnaire (MSQ)

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.

Time frame: from baseline to 1.2.3 month after treatment completion.

Mean Change From Baseline in the Headache Impact Test-6 (HIT-6 )

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.

Time frame: from baseline to 1.2.3 month after treatment completion.

Mean Change From Baseline in the Pittsburgh Sleep Quality Index(PSQI )

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.

Time frame: from baseline to 1.2.3 month after treatment completion.

Mean Change From Baseline in the Patient Global Impression of Change(PGIC )

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.

Time frame: from baseline to 3 month after treatment completion.

Mean Change From Baseline in the HAMD-24 (Hamilton Depression Rating Scale, 24-item).

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.

Time frame: from baseline to 1.2.3 month after treatment completion.

Mean Change From Baseline in the HAMA-14 (Hamilton Anxiety Rating Scale, 14-item).

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.

Time frame: from baseline to 1.2.3 month after treatment completion.

Metabolomics (Tryptophan and Kynurenine)

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.