Low-Intensity Focused Ultrasound Targeting the Dorsolateral Prefrontal Cortex for Preventive Treatment of Chronic Migraine

NCT07857109 | Not Yet Recruiting

• 1 other identifier: S2026-344-01
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic migraine is a disabling neurological disorder characterized by frequent headache attacks and significant impairment of quality of life. Low-intensity focused ultrasound (LIFUS) is a non-invasive neuromodulation technique that can precisely target deep brain regions. This study aims to evaluate the efficacy, safety, and tolerability of LIFUS targeting the left dorsolateral prefrontal cortex (DLPFC) for preventive treatment of chronic migraine in adults. This is a randomized, single-blind, sham-controlled clinical trial. Eligible participants with chronic migraine will be randomly assigned to receive either active LIFUS stimulation targeting the left DLPFC or sham stimulation. Participants will receive 10 stimulation sessions over 2 weeks and will be followed for 3 months after intervention. The primary outcome is the change in monthly migraine days from baseline to 1 month after intervention. Secondary and exploratory outcomes include headache-related disability, quality of life, psychological assessments, electrophysiological measurements, neuroimaging changes, and safety outcomes.

Conditions

Chronic Migraine Headache

Keywords

Migraine; Chronic Migraine; Low-Intensity Focused Ultrasound; Focused Ultrasound Neuromodulation

Outcome Measures

Primary Outcomes (1)

• Change in Monthly Migraine Days

  Change in monthly migraine days from baseline after intervention.

  Baseline and 1 month after intervention

Secondary Outcomes (14)

• Change in Acute Headache Medication Days

  Baseline and 1 month after intervention

• 50% Responder Rate Based on Monthly Migraine Days

  1 month after intervention

• 75% Responder Rate Based on Monthly Migraine Days

  1 month after intervention

• Change in Moderate/Severe Headache Days

  Baseline and 1 month after intervention

• Change in Visual Analog Scale (VAS) Score for Headache Intensity

  Immediately after each intervention session to 1 month after intervention

Other Outcomes (6)

• Long-term Change in Monthly Acute Headache Medication Days

  2 and 3 months after intervention

• Long-term Migraine Responder Rate (≥50%)

  2 and 3 months after intervention

• Long-term Change in Moderate/Severe Headache Days

  2 and 3 months after intervention

Study Arms (2)

DLPFC-LIFUS

EXPERIMENTAL

Device: Low-Intensity Focused Ultrasound Stimulation

DLPFC-Sham

SHAM COMPARATOR

Device: Sham Low-Intensity Focused Ultrasound Stimulation

Interventions

Low-Intensity Focused Ultrasound Stimulation DEVICE

Participants receive active low-intensity focused ultrasound stimulation targeting the left dorsolateral prefrontal cortex (DLPFC) for preventive treatment of chronic migraine.

DLPFC-LIFUS

Sham Low-Intensity Focused Ultrasound Stimulation DEVICE

Participants undergo sham stimulation procedures with identical positioning, coupling, and treatment duration as the active stimulation group, but without effective ultrasound output.

DLPFC-Sham

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants diagnosed with chronic migraine according to the International Classification of Headache Disorders, 3rd edition (ICHD-3), with a history of migraine for at least 12 months before screening.
• Migraine onset at or before 50 years of age.
• During the 3 months before screening, participants have headache occurring on at least 15 days per month, with migraine features or migraine-specific treatment on at least 8 days per month.
• During the baseline prospective electronic headache diary period, participants record at least 8 migraine days and 15 to 27 headache days.
• Participants are able to comply with electronic headache diary recording requirements, with data recorded for at least 24 of the 28 days during the screening period.
• Age between 18 and 65 years at screening visit.
• Participants are willing and able to provide written informed consent and comply with study procedures.

You may not qualify if:

• History of epilepsy, brain tumor, or traumatic brain injury.
• History of transcranial magnetic stimulation, transcranial direct current stimulation, or electroconvulsive therapy within the past 3 months.
• Presence of MRI-incompatible metallic implants, including but not limited to vascular stents, cardiac pacemakers, or ventriculoperitoneal shunts.
• Clinically significant comorbid chronic pain conditions, such as fibromyalgia, chronic low back pain, or complex regional pain syndrome.
• Diagnosis of acute or active temporomandibular disorder.
• History or diagnosis of other primary headache disorders, including chronic tension-type headache, hypnic headache, cluster headache, hemicrania continua, new daily persistent headache, or atypical migraine subtypes.
• Use of opioid-containing analgesics for more than 4 days within 1 month before baseline or during baseline period.
• Use of any migraine preventive medication within 1 month prior to screening.
• Use of devices or surgical interventions for migraine treatment within 1 month before baseline, including transcranial magnetic stimulation, greater occipital nerve block, or invasive/non-invasive neuromodulation procedures.
• History of malignant tumors within the past 5 years, except adequately treated localized basal cell carcinoma or carcinoma in situ of the cervix.
• History of severe psychiatric disorders, including schizophrenia, other psychotic disorders, bipolar disorder, obsessive-compulsive disorder, or post-traumatic stress disorder.
• Severe anxiety, depression, or manic symptoms according to predefined scale thresholds (SAS, SDS, and BRMS).
• Significant risk of self-harm or harm to others based on the Columbia Suicide Severity Rating Scale (C-SSRS) assessment or investigator judgment.
• History of myocardial infarction, stroke, transient ischemic attack, unstable angina, coronary artery bypass surgery, or other revascularization procedures within 12 months before screening.
• Pregnancy or breastfeeding.

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (1)

Chinese People's Liberation Army General Hospital, First Medical Center

Beijing, Beijing Municipality, China

Location

MeSH Terms

Conditions

Migraine Disorders

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Central Study Contacts

Zhao Dong, Doctor

CONTACT

(+86) 18910685535; dong_zhaozhao@126.com

Mingjie Zhang, Doctor

CONTACT

(+86) 18910276582; mjzhangnk@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 11, 2026
• First Posted: October 5, 2026
• Study Start: October 8, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): April 30, 2028
• Last Updated: October 5, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)