Stigma and Efficacy of Zhizhu Kuanzhong Capsules

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

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.

Study Overview

• Status: Recruiting
• Conditions: Dyspepsia; Functional Gastrointestinal Disorders; Psychosomatic Disorder
• Intervention / Treatment: Drug: Zhizhu Kuanzhong capsules (ZZKZ); Drug: Doxepin Hydrochloride (Doxepin)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 76
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sheng-Liang Chen, PhD; Phone Number: 021-53882113; Email: chenshengliang011774@renji.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • RenJi Hospital
      • Contact: Chen, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zhizhu Kuanzhong（ZZKZ） group; 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); FD patients were treated with ZZKZ and omeprazole for 4 weeks.; Other Names: Traditional Chinese medicine
Active Comparator: Doxepin group; 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); FD patients were treated with doxepin and omeprazole for 4 weeks.; Other Names: Antidepressants; Neuromodulators

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Investigators: Principal Investigator: Sheng-Liang Chen, PhD, Division of Gastroenterology and Hepatology, Renji Hospital

Publications and helpful links

General Publications

• Xiao Y, Li Y, Shu J, Li Y, Xu J, Ren J, Liu D, Wang J, Zhou L, Li Y, Tang G, Tian D, Zhang S, Hou X, Wang H, Li Z, Lv N, Chen M. The efficacy of oral Zhizhu Kuanzhong, a traditional Chinese medicine, in patients with postprandial distress syndrome. J Gastroenterol Hepatol. 2019 Mar;34(3):526-531. doi: 10.1111/jgh.14467. Epub 2018 Oct 12.
• Gwee KA, Holtmann G, Tack J, Suzuki H, Liu J, Xiao Y, Chen MH, Hou X, Wu DC, Toh C, Lu F, Tang XD. Herbal medicines in functional dyspepsia-Untapped opportunities not without risks. Neurogastroenterol Motil. 2021 Feb;33(2):e14044. doi: 10.1111/nmo.14044. Epub 2020 Nov 30.
• Yan XJ, Luo QQ, Qiu HY, Ji CF, Chen SL. The impact of stigma on medication adherence in patients with functional dyspepsia. Neurogastroenterol Motil. 2021 Feb;33(2):e13956. doi: 10.1111/nmo.13956. Epub 2020 Jul 27.
• Feingold JH, Drossman DA. Deconstructing stigma as a barrier to treating DGBI: Lessons for clinicians. Neurogastroenterol Motil. 2021 Feb;33(2):e14080. doi: 10.1111/nmo.14080. Epub 2021 Jan 23.
• Holtmann G, Talley NJ. Herbal medicines for the treatment of functional and inflammatory bowel disorders. Clin Gastroenterol Hepatol. 2015 Mar;13(3):422-32. doi: 10.1016/j.cgh.2014.03.014. Epub 2014 Mar 25.
• Black CJ, Drossman DA, Talley NJ, Ruddy J, Ford AC. Functional gastrointestinal disorders: advances in understanding and management. Lancet. 2020 Nov 21;396(10263):1664-1674. doi: 10.1016/S0140-6736(20)32115-2. Epub 2020 Oct 10.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Anticipated): August 1, 2022
• Study Completion (Anticipated): September 1, 2022

Study Registration Dates

• First Submitted: September 26, 2021
• First Submitted That Met QC Criteria: October 23, 2021
• First Posted (Actual): November 4, 2021

Study Record Updates

• Last Update Posted (Actual): August 10, 2022
• Last Update Submitted That Met QC Criteria: August 8, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Neurologic Manifestations; Signs and Symptoms, Digestive; Dyspepsia; Disease; Somatoform Disorders; Gastrointestinal Diseases; Digestive System Diseases; Psychophysiologic Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Psychotropic Drugs; Hypnotics and Sedatives; Antidepressive Agents, Tricyclic; Sleep Aids, Pharmaceutical; Histamine Antagonists; Histamine Agents; Doxepin; Antidepressive Agents; Neurotransmitter Agents
• Other Study ID Numbers: RJYYTCM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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