Low-Intensity Focused Ultrasound Targeting the Stellate Ganglion for Regulating Autonomic Nerve Function and Sleep Quality in Perioperative Patients With Cardiovascular Diseases (US-REST)

Low-Intensity Focused Ultrasound Targeting the Stellate Ganglion for Regulating Autonomic Nerve Function and Sleep Quality in Perioperative Patients With Cardiovascular Diseases: A Multicenter, Double-Blind, Randomized Controlled Trial

The goal of this multicenter, double-blind, randomized controlled trial is to evaluate the efficacy and safety of low-intensity focused ultrasound (LIFU) stellate ganglion modulation for improving autonomic function and sleep quality in perioperative cardiovascular disease patients.

The main questions it aims to answer are:

1. Does LIFU improve heart rate variability and sleep characteristics from baseline at 3-7 days post-surgery compared to sham ultrasound?
2. Does LIFU improve serological markers, vital signs, Pittsburgh Sleep Quality Index (PSQI), and reduce >30-second perioperative arrhythmias?
3. What is the safety profile of LIFU in this population? 200 eligible patients will be randomized 1:1 to receive either active LIFU (2.0W, 1MHz, 50% duty cycle, 30min daily for 3-7 days) plus standard care, or identical sham ultrasound plus standard care. A four-party double-blind design (subjects, operators, assessors, analysts) will be implemented. The study will run from May 1, 2026 to April 1, 2027 at 6 centers in China.

Participants will:

1. Complete pre-surgery screening and baseline assessments (PSQI, 12h ECG/sleep monitoring, residual blood sample collection)
2. Receive daily assigned ultrasound intervention for 3-7 consecutive days post-surgery
3. Undergo 72h continuous ECG monitoring post-surgery, and repeat assessments at 3-7 days
4. Have all adverse events and arrhythmias recorded throughout the study
5. May withdraw voluntarily at any time without affecting routine medical care

Study Overview

• Status: Not yet recruiting
• Conditions: Diagnosed With Cardiovascular Diseases and Scheduled to Undergo Interventional Cardiology Procedures
• Intervention / Treatment: Device: Low-intensity focused ultrasound (LIFU) targeting the left stellate ganglion; Device: Sham low-intensity focused ultrasound targeting the left stellate ganglion

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Songyun Wang, MD; Phone Number: +86 13871262107; Email: wsy7982@126.com

Study Locations

• China
  • Hubei
    • Huangshi, Hubei, China, 430060
      • Huangshi Central Hospital
      • Contact: Kai Zhang, MD; Phone Number: +86 13907230225; Email: zk9620@163.com
    • Jingzhou, Hubei, China, 430060
      • Jingzhou Central Hospital
      • Contact: Keping Yang, MD; Phone Number: +86 18107168679; Email: 30461400@qq.com
    • Wuhan, Hubei, China, 430060
      • Renmin Hospital of Wuhan University
      • Contact: Songyun Wang, MD; Phone Number: +86 13871262107; Email: wsy7982@126.com
    • Wuhan, Hubei, China, 430060
      • Wuhan Central Hospital
      • Contact: Long Wang, MD; Phone Number: +86 15761600527; Email: 319921605@qq.com
    • Wuhan, Hubei, China, 430060
      • Wuhan Third Hospital
      • Contact: Dongsheng Li, MD; Phone Number: +86 18872288277; Email: lidongsheng693@sina.com
    • Xiangyang, Hubei, China, 430060
      • Xiangyang Central Hospital
      • Contact: Tongjian Zhu, MD; Phone Number: +86 15971160197; Email: whuzhutongjian@126.com
    • Yichang, Hubei, China, 430060
      • Yichang Central People's Hospital
      • Contact: Zhuli Guo, MD; Phone Number: +86 15271455251; Email: guozhuli@yczxyy.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosed with cardiovascular disease (CVD) and scheduled to undergo cardiology-related surgical treatment
2. Able to receive and tolerate the aforementioned cardiology-related surgical treatment
3. Aged between 18 and 79 years (inclusive), with no restriction on gender
4. Agree to accept random allocation of the treatment strategies
5. With clear consciousness, no severe mental disorders or cognitive impairment; voluntarily sign the written informed consent form (ICF) and are willing to actively cooperate with the study treatment

Exclusion Criteria:

1. Have used sedative-hypnotic drugs, antipsychotic drugs, opioid analgesics, antihistamines, non-steroidal anti-inflammatory drugs (NSAIDs), central nervous system (CNS) stimulant drugs, or any other medications that alter sleep architecture within the past 30 days
2. Have a history of cervical infection, trauma, severe cervical deformity, or prior cervical surgery
3. Unable to complete the daily study intervention as required by the trial protocol
4. Are participating in another clinical trial, or have participated in other clinical trials with interventions that may interfere with the results of this study
5. Have undergone major surgery or general anesthesia within the past 30 days
6. Have a history of alcohol abuse
7. Are female subjects who are pregnant or lactating, or plan to become pregnant during the study period
8. Have severe cognitive impairment, severe psychiatric disorders, epilepsy, or other related neurological disorders
9. Have concomitant malignant tumor or severe dysfunction of vital organs
10. Have active systemic infection
11. Have significant bleeding tendency, or renal failure undergoing regular hemodialysis
12. Are deemed unsuitable for the trial by the investigator for any other reason -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-Intensity Focused Ultrasound (LIFU) Intervention Arm; Subjects in this arm will receive low-intensity focused ultrasound (LIFU) intervention on the left stellate ganglion. Ultrasound parameters: power 2.0 W, frequency 1 MHz, 50% duty cycle, 30 minutes per session, once daily for 3-7 consecutive days. All subjects will receive guideline-concordant standard perioperative cardiovascular care, including surgery and indicated medications.	Device: Low-intensity focused ultrasound (LIFU) targeting the left stellate ganglion; The experimental group receives active low-intensity focused ultrasound (LIFU) treatment: the ultrasound probe is placed on the skin surface corresponding to the left stellate ganglion and fixed with a mechanical arm, with parameters set as power 2.0W, frequency 1MHz, duty cycle 50%, 30 minutes per session, once daily for 3-7 consecutive days. All enrolled subjects receive standard perioperative cardiovascular care simultaneously throughout the study period.
Placebo Comparator: Sham Ultrasound Control Arm (Placebo); Subjects in this arm will receive sham ultrasound intervention with identical operational procedures, device appearance, and parameter settings (no actual energy output) as the intervention arm. Sessions are once daily for 3-7 consecutive days. All subjects will receive the same guideline-concordant standard perioperative cardiovascular care as the intervention arm.	Device: Sham low-intensity focused ultrasound targeting the left stellate ganglion; The control group receives sham low-intensity focused ultrasound intervention: the ultrasound probe is placed on the skin surface corresponding to the left stellate ganglion and fixed with a mechanical arm, with the same instrument appearance, operation process, parameter setting display (power 2.0W, frequency 1MHz, duty cycle 50%), duration (30 minutes per session, once daily for 3-7 consecutive days) and subject experience as the experimental group, but no actual ultrasound energy is output. All enrolled subjects receive standard perioperative cardiovascular care simultaneously throughout the study period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SDNN	Standard deviation of all normal-to-normal intervals measured by wearable Holter monitor; Unit: ms; Measurement device: wearable Holter monitors.	Pre-operative 24 hours and Post-operative 72 hours
Total sleep duration	Total sleep time measured by wearable sleep monitor; Unit: hours; Measurement device: Wearable sleep monitor.	Pre-operative 24 hours and Post-operative 72 hours
SDANN	Standard deviation of the averages of NN intervals in all 5-minute segments; Unit: ms; Measurement device: wearable Holter monitors.	Pre-operative 24 hours and Post-operative 72 hours
SDNN Index	Mean of the standard deviations of all NN intervals for all 5-minute segments; Unit: ms; Measurement device: wearable Holter monitors.	Pre-operative 24 hours and Post-operative 72 hours
RMSSD	Root mean square of successive differences between normal heartbeats; Unit: ms; Measurement device: wearable Holter monitors.	Pre-operative 24 hours and Post-operative 72 hours
pNN50	Percentage of successive NN intervals that differ by more than 50 ms; Unit: %; Measurement device: wearable Holter monitors.	Pre-operative 24 hours and Post-operative 72 hours
LF power	Low frequency power of heart rate variability; Unit: ms²; Measurement device: wearable Holter monitors.	Pre-operative 24 hours and Post-operative 72 hours
HF power	High frequency power of heart rate variability; Unit: ms²; Measurement device: wearable Holter monitors.	Pre-operative 24 hours and Post-operative 72 hours
TP	Total power of heart rate variability; Unit: ms²; Measurement device: wearable Holter monitors.	Pre-operative 24 hours and Post-operative 72 hours
LF/HF ratio	Ratio of low frequency to high frequency power; Unit: ratio; Measurement device: wearable Holter monitors.	Pre-operative 24 hours and Post-operative 72 hours
Wakefulness percentage	Percentage of time awake during sleep period; Unit: %; Measurement device: Wearable sleep monitor.	Pre-operative 24 hours and Post-operative 72 hours
Insomnia percentage	Percentage of time with insomnia symptoms during sleep period; Unit: %; Measurement device: Wearable sleep monitor.	Pre-operative 24 hours and Post-operative 72 hours
REM sleep percentage	Percentage of rapid eye movement sleep during total sleep time; Unit: %; Measurement device: Wearable sleep monitor.	Pre-operative 24 hours and Post-operative 72 hours
N1 sleep stage percentage	Percentage of N1 sleep stage during total sleep time; Unit: %; Measurement device: Wearable sleep monitor.	Pre-operative 24 hours and Post-operative 72 hours
N2 and N3 sleep stages percentage	Combined percentage of N2 and N3 sleep stages during total sleep time; Unit: %; Measurement device: Wearable sleep monitor.	Pre-operative 24 hours and Post-operative 72 hours
Sleep efficiency	Ratio of total sleep time to time in bed; Unit: %; Measurement device: Wearable sleep monitor.	Pre-operative 24 hours and Post-operative 72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IL-1β level	Serum IL-1β concentration; Unit: pg/mL.	Pre-operative 24 hours and Post-operative 72 hours
Norepinephrine (NE) level	Serum norepinephrine concentration; Unit: pg/mL.	Pre-operative 24 hours and Post-operative 72 hours
Brain-derived neurotrophic factor (BDNF) level	Serum brain-derived neurotrophic factor concentration; Unit: pg/mL.	Pre-operative 24 hours and Post-operative 72 hours
Pittsburgh Sleep Quality Index (PSQI) score	Subjective sleep quality assessed using the Pittsburgh Sleep Quality Index questionnaire; Unit: Score on a 0-21 scale, where higher scores indicate worse sleep quality; Method of Measurement: Self-administered questionnaire.	Pre-operative 24 hours and Post-operative 72 hours
Number of atrial arrhythmias	Measurement: count of atrial arrhythmia episodes. Measurement device: wearable Holter monitors.	Pre-operative 24 hours and Post-operative 72 hours
Duration of atrial arrhythmias	Measurement: Duration of atrial arrhythmia episodes. Measurement device: wearable Holter monitors.	Pre-operative 24 hours and Post-operative 72 hours
TNF-α level	Serum TNF-α concentration; Unit: pg/mL.	Pre-operative 24 hours and Post-operative 72 hours
Neuropeptide Y (NPY) level	Serum neuropeptide Y concentration; Unit: pg/mL.	Pre-operative 24 hours and Post-operative 72 hours
Melatonin level	Serum melatonin concentration; Unit: pg/mL.	Pre-operative 24 hours and Post-operative 72 hours

Collaborators and Investigators

• Sponsor: Renmin Hospital of Wuhan University
• Collaborators: Yichang Central People's Hospital; Wuhan Central Hospital; Xiangyang Central Hospital; Wuhan Third Hospital; Jingzhou Central Hospital; Huangshi Central Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 5, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: April 28, 2026
• First Submitted That Met QC Criteria: May 12, 2026
• First Posted (Actual): May 19, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Cardiovascular Diseases; Sleep Quality; Stellate Ganglion; Low-Intensity Focused Ultrasound; Autonomic Nervous Function
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Cardiovascular Diseases; Sleep Initiation and Maintenance Disorders
• Other Study ID Numbers: WDRY2026-K085; 82570593 (Other Grant/Funding Number: National Natural Science Foundation of China (NSFC))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Due to considerations for protecting participant privacy, undetermined data ownership, or the absence of a detailed data-sharing policy.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No