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

Official title

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

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.

Interventions

• Device Individualized location-based Repetitive Transcranial Magnetic Stimulation
  Enhancing targeting accuracy through personalized target localization to improve the analgesic response rate of rTMS.
• 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.

Primary outcome measures

• Change in the monthly average number of migraine days [Time frame: from baseline to 1 month after treatment completion.]

Secondary outcome measures (12)

• Change in the monthly average number of migraine days [Time frame: 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.]
• 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.]
• Mean Change From Baseline in the Headache Impact Test-6 (HIT-6 ) [Time frame: 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.]
• Mean Change From Baseline in the Patient Global Impression of Change(PGIC ) [Time frame: 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.]
• 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.]
• Metabolomics (Tryptophan and Kynurenine) [Time frame: Treatment completion (2 weeks) vs. baseline.]
• Mean Change From Baseline in Inflammatory Biomarker Levels. [Time frame: Treatment completion (2 weeks) vs. baseline.]
• Mean Change From Baseline in Glutamate, Endocannabinoids and Related Lipids [Time frame: Treatment completion (2 weeks) vs. baseline.]
• Mean Change From Baseline in Gut Microbiota Composition [Time frame: Treatment completion (2 weeks) vs. baseline.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou

Identifiers

NCT: NCT07086274 · [2025C]IIT. No. 013

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗