Right Dorsolateral Prefrontal Cortex Closed-loop Neurofeedback for Anxiety in High-ischaemic-risk Chronic Coronary Syndrome

NCT07543185 | Not Yet Recruiting DMC

• 1 other identifier: HEART-SET-3
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective, randomized, sham-controlled, participant- and assessor-blinded, parallel-group clinical trial designed to evaluate the clinical efficacy, mechanistic effects, and safety of right dorsolateral prefrontal cortex (DLPFC) closed-loop functional near-infrared spectroscopy brain-computer interface (fNIRS-BCI) neurofeedback in patients with high-ischaemic-risk chronic coronary syndrome (CCS) and comorbid anxiety disorder. Participants will be randomly assigned in a 1:1 ratio to active neurofeedback or sham feedback. The intervention consists of 4 weeks of treatment, with 20 sessions in total (1 session per weekday, approximately 20 minutes per session). The primary endpoint is the between-group difference in Hamilton Anxiety Rating Scale (HAMA) score at 3 months after treatment. Secondary endpoints include HAMA score and HAMA response rate at the end of treatment, as well as neurophysiological measures collected during Session 1, including right DLPFC activation, heart rate (HR), and heart rate variability (HRV). Exploratory long-term follow-up will assess cardiovascular and bleeding outcomes through 4 years after randomization.

Conditions

Chronic Coronary Syndrome; Anxiety Disorder; High Ischemic Risk

Keywords

closed-loop neurofeedback; fNIRS-BCI; right dorsolateral prefrontal cortex; psycho-cardiology

Outcome Measures

Primary Outcomes (1)

• Hamilton Anxiety Rating Scale (HAMA) total score at 3 months after treatment

  Between-group difference in Hamilton Anxiety Rating Scale (HAMA) total score at 3 months after treatment. Lower scores indicate less severe anxiety symptoms.

  3 months after completion of the 4-week treatment period

Secondary Outcomes (6)

• Hamilton Anxiety Rating Scale (HAMA) total score at end of treatment

  At the end of Week 4 of treatment

• HAMA response rate at end of treatment

  At the end of Week 4 of treatment

• HAMA response rate at 3 months after treatment

  3 months after completion of the 4-week treatment period

• Baseline-corrected heart rate change during the first treatment day

  Day 1 of Week 1 of the 4-week treatment period

• Right dorsolateral prefrontal cortex HbO activation during the first treatment day

  Day 1 of Week 1 of the 4-week treatment period

Other Outcomes (8)

• Indirect effect of treatment group on heart rate change mediated by right DLPFC activation

  Day 1 of Week 1 of the 4-week treatment period

• Indirect effect of treatment group on anxiety improvement mediated by heart rate change

  3 months after completion of the 4-week treatment period

• Time to first major adverse cardiovascular event composite endpoint

  From randomization through 4 years after randomization

Study Arms (2)

Active closed-loop neurofeedback

EXPERIMENTAL

Participants assigned to this arm receive active right dorsolateral prefrontal cortex (DLPFC) closed-loop fNIRS-BCI neurofeedback. Treatment consists of 20 sessions over 4 weeks (1 session per weekday, approximately 20 minutes per session). The feedback signal is meaningfully coupled to real-time right DLPFC activity. Session 1 includes synchronized ECG recording for HR and HRV assessment.

Device: Active right DLPFC closed-loop fNIRS-BCI neurofeedback

Sham neurofeedback

SHAM COMPARATOR

Participants assigned to this arm undergo procedures identical to the active arm, including the same visit schedule, auditory cues, training duration, interface appearance, and follow-up assessments. Treatment consists of 20 sessions over 4 weeks (1 session per weekday, approximately 20 minutes per session). The feedback signal is not meaningfully coupled to real-time right DLPFC activity. Session 1 includes synchronized ECG recording for HR and HRV assessment.

Device: Sham right DLPFC closed-loop fNIRS-BCI neurofeedback

Interventions

Active right DLPFC closed-loop fNIRS-BCI neurofeedback DEVICE

A closed-loop functional near-infrared spectroscopy brain-computer interface (fNIRS-BCI) neurofeedback intervention targeting the right dorsolateral prefrontal cortex (DLPFC). Participants receive 20 sessions over 4 weeks, delivered once daily on weekdays, with each session lasting approximately 20 minutes. The training uses a 60-second cycle consisting of 20 seconds of rest and 40 seconds of auditory cueing, with a 1 Hz sinusoidally amplitude-modulated pure tone as the main cue. During training, the system provides real-time feedback coupled to right DLPFC hemodynamic activity to guide intentional downregulation.

Active closed-loop neurofeedback

Sham right DLPFC closed-loop fNIRS-BCI neurofeedback DEVICE

A sham closed-loop functional near-infrared spectroscopy brain-computer interface (fNIRS-BCI) neurofeedback condition delivered with procedures identical to the active intervention, including the same visit schedule, auditory cues, training duration, interface appearance, and follow-up assessments. Participants receive 20 sessions over 4 weeks, delivered once daily on weekdays, with each session lasting approximately 20 minutes. The feedback signal is not meaningfully coupled to real-time right DLPFC activity.

Sham neurofeedback

Eligibility Criteria

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

You may qualify if:

• Participants will be aged 18 years or older and will provide written informed consent.
• Participants will have chronic coronary syndrome (CCS) with prior coronary stent implantation more than 6 months before enrollment.
• Participants will meet high ischemic risk (HIR) criteria by either of the following:
• Percutaneous coronary intervention (PCI) performed more than 6 months earlier for acute coronary syndrome (ACS), including unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction, with implantation of at least 1 coronary stent; or
• PCI performed more than 6 months earlier for a non-ACS indication, together with at least 1 of the following risk factors:
• diabetes mellitus;
• diffuse multivessel coronary artery disease involving all 3 major coronary vessels;
• chronic kidney disease with creatinine clearance less than 50 mL/min (recommended to be calculated using the Cockcroft-Gault formula);
• prior stent thrombosis;
• peripheral arterial disease;
• complex PCI, defined by at least 1 of the following:
• only patent remaining coronary vessel or left main coronary artery stenting;
• implantation of at least 3 stents or treatment of at least 3 lesions;
• bifurcation lesion treated with a 2-stent strategy;
• total stent length greater than 60 mm;

You may not qualify if:

• Participants will be excluded if they have severe congestive heart failure (New York Heart Association class IV).
• Participants will be excluded if they have moderate-to-severe valvular heart disease.
• Participants will be excluded if they have a history of atrial fibrillation.
• Participants will be excluded if they have unstable blood pressure, defined as systolic blood pressure greater than 180 mmHg or less than 90 mmHg.
• Participants will be excluded if they are pregnant or breastfeeding.
• Participants will be excluded if they have active or recent (within 6 months) severe systemic disease, including any of the following:
• cerebrovascular disease, including stroke or transient ischemic attack;
• dementia or severe cognitive impairment;
• hyperthyroidism;
• active pulmonary disease;
• active malignant tumor.
• Participants will be excluded if they have suicidal or homicidal risk based on clinical interview.
• Participants will be excluded if they have other severe psychiatric disorders, including but not limited to:
• psychotic disorders, such as hallucinations or delusions;
• bipolar disorder.

Sponsors & Collaborators

• Shenyang Medical College: lead

Study Sites (1)

Second Affiliated Hospital of Shenyang Medical College

Shenyang, Liaoning, 110001, China

Location

MeSH Terms

Conditions

Anxiety Disorders

Condition Hierarchy (Ancestors)

Mental Disorders

Study Officials

• Lin Tao, Assoc.Prof.

  Shenyang Medical College

  PRINCIPAL INVESTIGATOR

• Yun-En Liu, MD

  Shenyang Medical College

  STUDY CHAIR

Central Study Contacts

Yun-En Liu, MD

CONTACT

86-24-62215130; lye9901@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants and outcome assessors are masked to treatment assignment. The intervention operator may know the assigned condition only to administer the neurofeedback system correctly, but does not perform outcome assessment or statistical analysis. Both groups undergo identical visit schedules, auditory cues, training duration, interface appearance, and follow-up procedures; the only difference is whether the feedback signal is meaningfully coupled to real-time right DLPFC activity.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc.Prof.

Model Details: Eligible participants with high-ischaemic-risk chronic coronary syndrome and comorbid anxiety disorder are randomized 1:1 to active right DLPFC closed-loop fNIRS-BCI neurofeedback or sham feedback. The intervention consists of 20 sessions delivered over 4 weeks. The primary endpoint is the between-group difference in HAMA score at 3 months after treatment. Long-term cardiovascular and bleeding outcomes are followed exploratorily through Year 4 after randomization.

Study Record Dates

• First Submitted: April 14, 2026
• First Posted: April 21, 2026
• Study Start: April 19, 2026
• Primary Completion (Estimated): June 20, 2027
• Study Completion (Estimated): February 20, 2031
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

CN (1)