Anshen Buxin Liuwei Pills for the Treatment of Cardiac Neurosis

Study Overview
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Brief Summary
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This study aims to assess the effect and safety of the traditional Mongolian medicine Anshen Buxin Liuwei Pill for the treatment of cardiac neurosis.

Detailed Description
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Cardiac neurosis is a group of symptoms characterized by the coexistence of cardiovascular disease related symptoms and nervous system disorders. Anshen Buxin Liuwei Pill is a kind of traditional Mongolian medicine for the treatment of cardiac neurosis. This study aims to evaluate the effect and safety of Anshen Buxin Liuwei Pill for cardiac neurosis in a prospective, randomized, double-blind, placebo-controlled clinical trial.

Official Title
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An Adaptive Enrichment Designed, Multi-center, Randomized, Double-blind, Placebo-controlled Clinical Trial of Anshen Buxin Liuwei Pills in the Treatment of Cardiac Neurosis

Conditions
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Cardiac Neurosis

Intervention / Treatment
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* Drug: Anshen Buxin Liuwei Pill
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years old, ≤75 years old; Meet the diagnostic criteria for cardiac neurosis: the patient has palpitations, precordial pain, chest tightness, shortness of breath, dyspnea, dizziness, insomnia and dreaminess, cold hands and feet, hyperhidrosis and other cardiovascular symptoms and neurological disorders; Meet the diagnostic criteria of Heyisheng type palpitations in Mongolian medicine; There is no objective diagnosis of coronary heart disease (in accordance with any of the following): ①The activity flat test is negative; ② Coronary angiography or coronary CTA suggests that the lumen stenosis is ≤50%; ③ Exercise or drug load radionuclide examination results suggest no myocardial ischemia; The patient did not take anti-anxiety and depression drugs or psychotropic drugs within 2 weeks before enrollment; agrees to voluntarily participate in the study and signs an informed consent form . Exclusion Criteria: Accompanied by organic heart disease, severe cardiopulmonary insufficiency; Poor hypertension control (systolic blood pressure ≥160mmHg or diastolic blood pressure ≥100mmHg after treatment); Those with malignant arrhythmia; Those who use pacemakers; Patients with hyperthyroidism; Combined with severe liver and kidney damage (ALT, AST or TBIL> 2 times the upper limit of the normal reference value, or Cr> 1.5 times the upper limit of the normal reference value); People with serious primary diseases such as hematopoietic system or mental illness; SAS≥70; SDS≥73; Accompanying any other serious diseases or conditions such as malignant tumors; Women during pregnancy and lactation; People with allergies or allergies to the known ingredients of the research drug; Participated in other clinical research in the past 3 months; According to the judgment of the investigator, the subject is not suitable for research observation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anshen Buxin Liuwei Pills<br>15 pills/time, 2 times/day, orally，for 8 weeks | Drug: Anshen Buxin Liuwei Pill<br>* 15 capsules/time, 2 times/day, orally.<br>|
| Placebo Comparator: Placebo<br>15 pills/time, 2 times/day, orally. for 8 weeks | Drug: Placebo<br>* Placebo simulated as the Anshen Buxin Liuwei Pills with same appearance，smell and taste,15 capsules/time, 2 times/day, orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Palpitation with Heyisheng Type Symptoms Scale in Mongolian Medicine | The scale is to record the symptoms of palpitation with Heyisheng Type in Mongolian Medicine, which is also usually seen in cardiac neurosis. This scale includes two domain: the primary symptoms and the secondary symptoms. The domain of the primary symptoms includes palpitations, chest tightness, chest pain, insomnia, and restlessness using the evaluating 4-Grade scales (Normal:0; Mild:3; Moderate:6 and Severe:9), while the domain of the secondary symptoms includes dizziness, like to sigh, easy to startle, tinnitus, blurred vision, fatigue, sweating, irritability, using the evaluating 4-Grade scales (Normal:0; Mild:1; Moderate:2 and Severe:3). | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac autonomic nervous function | The cardiac autonomic nervous function was evaluated by detecting the difference in heart rate per minute between standing and lying positions using RR interval in lead Ⅱ ECG. | Baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks. | 
| Cardiac Neurosis Symptom Self-rating Scale | This self-rating scale was used to evaluate the main symptoms in cardiac neurosis, including palpitations, chest tightness, chest pain, hyperhidrosis, insomnia, irritability, with each symptom evaluated via a 4-grading scale (normal:0 points, mild: 1 point, moderate: 2 points, severe:3 points | Baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks. | 
| Self-rating depression scale (SDS) | The Self-Rating Depression Scale (SDS) which was designed by Zung was adopted to assess participants' symptoms of depression during the past week. The SDS assesses depressive symptoms on a four-point scale ranging from a little of the time (value = 1) to most of the time (value = 4). The standard score is equal to the integer portion of 1.25 times the total score. The standard score of SDS is interpreted as: normal (≤52), mild (53-62), moderate (63-72), and severe (≥73). | Baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks. | 
| Self-rating Anxiety Scale (SAS) | The SAS is a 20-item measure developed to assess the frequency of anxiety symptoms based on diagnostic conceptualizations. It consists primarily of somatic symptoms. The respondent indicates how often he or she has experienced each symptom on a 4-point Likert scale consisting of one or a little of the time (coded as 1), some of the time (coded as 2), good part of the time (coded as 3), and most or all of the time (coded as 4). Items 5, 9, 13, 16, and 19 are reversed scored and total scores on the SAS range from 0 to 80. | Baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks. | 
| Pittsburgh Sleep Scale Score | The PSQI comprises 19 self-evaluation items, among which 18 items generate 7 components. Each component is graded from 0 to 3, and the cumulative score of each component is the total score of PSQI, which ranges from 0 to 21. | Baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks. | 
| Consumption of estazolam | If the patient has a moderate or above anxiety and depression state and is intolerable, he could be given a short-term sedative and hypnotic drug,estazolam, and the frequency and dose of estazolam should be recorded in the patient's diary | Baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks. | 
| hypersensitive C-reactive protein (hs-CRP) | hs-CRP is used to evaluate the level of systemic inflammation in the patients with cardiac neurosis. | Baseline, 4 weeks, 8 weeks | 
| The level of serotonin | The decrease of serotonin is reported in the patients with cardiac neurosis. The level of serotonin could be used to evaluate the effect for cardiac neurosis. | Baseline, 4 weeks, 8 weeks |