Optimizing Parameters of Low-Intensity Focused Ultrasound for Pallidal Modulation in Huntington's Disease

NCT07513844 | Recruiting

• 1 other identifier: MRCTA,ECFAH of FMU[2025]738-1
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to determine the optimal pulse repetition frequency of low-intensity focused ultrasound that is safe and effective in improving motor symptoms in patients with Huntington's disease.

Conditions

Huntington Disease

Keywords

low intensity focused ultrasound; Huntington Disease; brain stimulation; ultrasonic stimulation

Outcome Measures

Primary Outcomes (3)

• Safety: Incidence of Dose-Limiting Toxicity (DLT)

  DLT refers to the occurrence of any of the following six events during LIFU treatment: 1. Second-degree scalp burn; 2. Clinical seizure; 3. Worsening of chorea or new movement disorder; 4. Significant deterioration of the patient's mood or mental status (e.g., anxiety, depression, hallucinations, excessive sleepiness); 5. Severe autonomic dysfunction, such as marked blood pressure fluctuations, abnormal heart rate, or respiratory distress; 6. Imaging-related safety events: new or significantly enlarged brain edema, new microbleeds, new infarcts, or structural abnormalities in the treatment area on post-treatment cranial MRI compared with baseline, deemed clinically significant by both radiologists and clinicians.

  At any point during or immediately following intervention on day of LIFUS application

• Efficacy: Change in Unified Huntington's Disease Rating Scale Total Motor Score (UHDRS-TMS)

  The Unified Huntington's Disease Rating Scale Total Motor Score (UHDRS-TMS) evaluates motor impairment in Huntington's disease. Score range: 0-124 Higher scores indicate more severe motor impairment Response is defined as a reduction of ≥4 points from baseline.

  Baseline and within 2 days after completing the 5-day LIFU treatment

• Comprehensive Benefit-Risk: Utility

  Utility is a composite measure integrating dose-limiting toxicity (DLT) and efficacy response to quantify the overall benefit-risk balance for each dose group. During the trial, the Utility value for each dose group is dynamically calculated using the U-BOIN design platform. In Stage II, the Utility value determines dose allocation for subsequent cohorts. At study completion, the dose group with the highest Utility value is identified as the optimal biological dose.

  Within 2 days after completing the 5-day LIFU treatment

Other Outcomes (11)

• Patient Global Impression of Change (PGI-C)

  Within 2 days after completing the 5-day LIFU treatment

• Clinical Global Impression of Change (CGI-C)

  Within 2 days after completing the 5-day LIFU treatment

• Change in Unified Huntington's Disease Rating Scale Chorea Score

  Baseline and within 2 days after completing the 5-day LIFU treatment

Study Arms (3)

10 Hz LIFU Group

EXPERIMENTAL

Low-Intensity Focused Ultrasound (LIFU), PRF 10 Hz

Device: Low-Intensity Focused Ultrasound Stimulation（LIFU）

50 Hz LIFU Group

EXPERIMENTAL

Low-Intensity Focused Ultrasound (LIFU), PRF 50 Hz

Device: Low-Intensity Focused Ultrasound Stimulation（LIFU）

100 Hz LIFU Group

EXPERIMENTAL

Low-Intensity Focused Ultrasound (LIFU), PRF 100 Hz

Device: Low-Intensity Focused Ultrasound Stimulation（LIFU）

Interventions

Low-Intensity Focused Ultrasound Stimulation（LIFU） DEVICE

This is not a traditional three-arm parallel trial but a Stage I/II dose-finding study using an adaptive design. Participants are dynamically assigned to three pulse repetition frequency levels (10 Hz, 50 Hz, 100 Hz) based on predefined rules, rather than fixed randomization. The study adopts a two-stage utility-based Bayesian optimal interval (U-BOIN) design: Stage I: Dose decisions are based solely on dose-limiting toxicity (DLT) incidence. Participants are enrolled in cohorts of three. Based on observed DLTs, the next cohort's dose is determined (escalate/stay/de-escalate). Stage II: When any dose group reaches 6 participants or the highest dose is explored, safety and efficacy data are integrated to calculate a utility value. Subsequent cohorts are assigned to the dose group with the highest utility value. The study stops when any dose group reaches 12 participants or total enrollment reaches 24. Not all three dose levels may be utilized. Allocation is not fixed a priori.

10 Hz LIFU Group; 100 Hz LIFU Group; 50 Hz LIFU Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 75 years (inclusive)
• Genetically confirmed Huntington's disease with HTT CAG repeat length of 40 or greater
• Unified Huntington's Disease Rating Scale Total Maximal Chorea score of 8 or higher on a scale of 0 to 28, with higher scores indicating more severe chorea
• Huntington's Disease Integrated Staging System stage 2 or 3
• Willing to participate and provide informed consent
• Have a reliable caregiver available
• No severe cognitive impairment that would preclude reliable reporting of adverse events or efficacy during treatment

You may not qualify if:

• History of self-injury, aggressive behavior, or unstable psychiatric disorders
• History of head injury or neurosurgical procedure
• Presence of intracranial implants, metallic foreign bodies, cochlear implants, or cardiac pacemakers
• Severe systemic disease, pregnancy, or breastfeeding
• Contraindications to magnetic resonance imaging, ultrasound, or anesthesia
• Prior treatment with electroconvulsive therapy, transcranial magnetic stimulation, transcranial direct current stimulation, transcranial alternating current stimulation, or other neuromodulation therapies within the past 3 years
• Severe brain atrophy with unclear external globus pallidus structure on MRI
• Concurrent participation in another interventional clinical trial
• Any other condition that, in the opinion of the investigator, would preclude participation

Sponsors & Collaborators

• First Affiliated Hospital of Fujian Medical University: lead

Study Sites (1)

Department of Rehabilitation Medicine, The First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, China

RECRUITING

MeSH Terms

Conditions

Huntington Disease

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Xin-Yuan Chen

CONTACT

+86 15005065282; fychenxinyuan@fjmu.edu.cn

Li-Zhu Wu

CONTACT

+86 18459867658; 1809225097@qq.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending Physician

Study Record Dates

• First Submitted: March 24, 2026
• First Posted: April 7, 2026
• Study Start: April 20, 2026
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: April 29, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)