Stigma and Efficacy of Zhizhu Kuanzhong Capsules

Study Overview
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Brief Summary
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Antidepressants are effective in patients with functional dyspepsia (FD), however, the stigma related with FD and antidepressants could affect treatment adherence and efficacy. Zhi Zhu Kuan Zhong capsules (ZZKZ), a traditional Chinese medicine fomula, showed therapeutic potential for FD. The study was designed to investigate whether ZZKZ could alleviate stigma in FD and obtain identical effects in patients with refractory FD.

Detailed Description
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Patients with dyspepsia have poor quality of life and emotional distress. The pathophysiology of FD is complex and multifactorial, including factors related to central nervous system and peripheral sensory system. Abundant drugs have been trialed to treat FD patients, but the treatment options remain limited and far from optimal. Antidepressants were beneficial in the treatment of FD. But the antidepressant prescriptions often aggravate the stigma of patients with FD, hinder doctor-patient communication, and reduce treatment compliance. Some patients with strong stigmatized feelings towards antidepressants refused to take the medications, and stigma related with antidepressants could ultimately affect the efficacy of FD. Zhizhu Kuanzhong capsules (ZZKZ), a commonly used traditional Chinese medicine (TCM) formula, had shown effectiveness in relieving dyspeptic symptoms. It has a long culture and history in promoting the function of brain and GI tract in whole, which is widely accepted by populations who were familiar with TCM. The study was designed to observe whether ZZKZ could alleviate stigma of patients and obtain identical effects in patients with FD, therefore provide a new insight in the treatment of FD.

Official Title
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Stigma and Efficacy of Zhizhu Kuanzhong Capsules Versus Doxepin in the Treatment of Refractory Functional Dyspepsia: a Randomized Controlled Trial

Conditions
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Functional Gastrointestinal Disorders, Dyspepsia, Psychosomatic Disorder

Intervention / Treatment
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* Drug: Zhizhu Kuanzhong capsules (ZZKZ)
* Drug: Doxepin Hydrochloride (Doxepin)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The inclusion criteria includes: 18-70 years old; education level higher than middle school; met the Rome IV criteria for FD; absence of abnormalities on physical examination, laboratory tests (including a routine blood test, blood glucose, and liver function examination), and abdominal imaging and GI endoscopy within 6 months; absence of Helicobacter pylori infection; signed written informed consent for participation in the study. Exclusion Criteria: The exclusion criteria includes: evidence of organic digestive diseases; diabetes, cancer and other diseases might affect GI function; pregnancy, lactation or breastfeeding; a history of allergic reaction to any of the drugs used in the study; participation in other clinical trials in the previous 3 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Interventional Model Description: Zhizhu Kuanzhong (ZZKZ) group was treated with ZZKZ capsules with omeprazole. Antidepressant group was treated with doxepin with omeprazole.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zhizhu Kuanzhong（ZZKZ） group<br>Patients in ZZKZ group were given ZZKZ (2 capsules tid) plus omeprazole (20 mg bid). ZZKZ was applied after each meal. Omeprazole was applied twice daily, before breakfast and supper. | Drug: Zhizhu Kuanzhong capsules (ZZKZ)<br>* FD patients were treated with ZZKZ and omeprazole for 4 weeks.<br>* Other names: Traditional Chinese medicine;|
| Active Comparator: Doxepin group<br>Patients in doxepin group were given doxepin (25 mg tid) plus omeprazole (20 mg bid). Doxepin was applied after each meal. Omeprazole was applied twice daily, before breakfast and supper. | Drug: Doxepin Hydrochloride (Doxepin)<br>* FD patients were treated with doxepin and omeprazole for 4 weeks.<br>* Other names: Antidepressants;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of Leeds Dyspepsia Questionnaire (LDQ) scores at 4 weeks from baseline were obtained to assess the dyspepsia condition after treatment. | The LDQ scores of 0-4 were classified as very mild dyspepsia, 5-8 as mild dyspepsia, 9-15 as moderate dyspepsia, and >15 as severe or very severe dyspepsia. | 4 weeks | 
| Changes of Patient Health Questionnaire-9 (PHQ-9) scores at 4 weeks from baseline were obtained to assess the depression condition after treatment. | The PHQ-9 scores of 0-4 were classified as none or minimal depression, 5-9 as mild, 10-14 as moderate, 15-19 as moderately severe, and ≥20 as severe depression. | 4 weeks | 
| Changes of Generalized Anxiety Questionnaire-7 (GAD-7) scores at 4 weeks from baseline were obtained to assess the anxiety condition after treatment. | The GAD-7 scores of 0-4 were classified as the absence of anxiety, 5-9 as mild, 10-14 as moderate, and ≥15 as severe. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of Internalized stigma scale (ISS) scores at 4 weeks from baseline were obtained to assess the internalized stigma of patients after treatment. | The Internalized stigma scale (ISS) is a 24-item self-report questionnaire with items ranked on a 4-point Likert scale (strongly disagree = 1 to strongly agree = 4 points). The ISS scores are calculated by summing the values for each item and dividing by the number of questions answered for each scale. Higher scores indicate higher levels of ISS. The ISS scores of 1-2 were classifies as minimal, 2-2.5 as mild, 2.5-3 as moderate, 3-4 as severe. | 4 weeks | 
| Changes of Perceived stigma scale (PSS) scores at 4 weeks from baseline were obtained to assess the perceived stigma of patients after treatment. | The Perceived stigma scale (PSS) is a 10-item questionnaire with items ranked on a 5-point Likert scale (seldom = 1 to always = 5 points). The scores are calculated by summing the values for each item and dividing by the number of questions answered for each scale. Minimum to maximum score is 1 to 5 points. Higher scores indicate higher levels of PSS. The PSS scores of 1-2 were classifies as minimal, 2-3 as mild, 3-4 as moderate, 4-5 as severe. | 4 weeks |