Traditional Chinese Medicine on Gut Microbiota and Allergic Diseases

Effect of Traditional Chinese Medicine on Gut Microbiota, Physical Constitution, and Allergic Diseases

Allergic rhinitis is an importance disease in Taiwan with its high incidence about 20-30% and gradually increased annually. However, symptom relapse still bothered the majority of patients though there were certain advances in western medicine. In addition, side effects of western medicine, such as lethargy, mouth dryness were noted. Traditional Chinese medicine, especially qi-tonifying regimen has been used and proved benefit to the allergic diseases by many researchers.This study will provide the evidences of gut microbiota changes and immune-modulatory effects of BZYQT for the treatment of allergic rhinitis.

Study Overview

• Status: Unknown
• Conditions: Allergic Rhinitis
• Intervention / Treatment: Drug: Bu-Zhong-Yi-Qi-Tang; Drug: placebo

Detailed Description

Recently studies reported that gut microbiota is related to the human immunity modulation of allergic diseases. Investigators are interested to know weather qi-tonifying herbal medicine is through the changes of gut microbiota to modulate human immunity. In this study, a double-blinded, randomized, placebo control design is applied and total 60 perennial allergic rhinitis patients will be enrolled in our study. All subjects will be divided into Bu-Zhong-Yi-Qi-Tang (BZYQT) and placebo control groups, 40 and 20 subjects each. Subjects of BZYQT group will receive capsule of BZYQT, 4gm tid, 12gm a day, while control group will receive similar placebo capsule with same scheme. Total 2 months treatment course will be done. Gut microbiota will be assayed before and after 2 months treatment. Additionally, various parameters for immunologic response will be checked before and after the treatment, including the total IgE amount, the ratio of CD4/CD8 of T lymphocytes, the profile of cytokine such as IL-10 and IL-12 as well as functional change of dendritic cells and T cells. Results will be analyzed statistically including gender analysis. This study will provide the evidences of gut microbiota changes and immune-modulatory effects of BZYQT for the treatment of allergic rhinitis.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sien-hung Yang, Ph.D.; Phone Number: 2611 +886-3-3196200; Email: dryang@ms1.hinet.net
• Study Contact Backup: Name: Yi-Hsuan Lin, M.D.; Phone Number: 2611 +886-3-3196200; Email: cynthiajobo@gmail.com

Study Locations

• Taiwan
  • Taoyuan, Taiwan
    • Recruiting
    • Chang Gung Memorial Hospital
    • Contact: Yi-Hsuan Lin, M.D.; Phone Number: 2611 +886-3-3196200; Email: cynthiajobo@gmail.com
    • Principal Investigator: Sien-hung Yang, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. With at least one of the following clinical symptoms: itchy nose, sneeze, rhinorrhea, nasal congestion
2. Diagnosed as intermittent allergic rhinitis (Less than 4 days per week and for less than 4 weeks)
3. CAP panel :allergy to mite
4. Will to complete questionnaires and take medicine as schedule in this study
5. Volunteer for study enrollment and sign inform consent

Exclusion Criteria:

1. Under treatment of western medicine including steroid, antihistamine, leukotriene inhibitor, immunosuppressant or stop above medication less than one month
2. Under acute inflammatory disease such as pneumonia, sinusitis, bronchitis and so on
3. vasomotor type allergic rhinitis
4. history of allergy or adverse effect to Chinese herbs, poor compliance of herbal medicine
5. severe organ function impairment, such as heart failure, liver failure, renal failure (eGFR <60 mL/min/1.73 m2)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bu-Zhong-Yi-Qi-Tang (BZYQT); capsule of BZYQT, 4gm tid, 12gm a day for 2 months	Drug: Bu-Zhong-Yi-Qi-Tang; Qi-tonifying regimen of traditional Chinese herbal medicine
Placebo Comparator: placebo control; similar placebo capsule 4gm tid, 12gm a day for 2 months	Drug: placebo; placebo control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in allergic rhinitis symptom severity	Sino-nasal Outcome Test (SNOT-22)	Assessment of symptom severity on Day 0 and 2 months after completing treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of fatigue	Fatigue Severity Scale	Assessment of fatigue severity on Day 0 and 2 months after completing treatment
Improvement of life quality	SF-36	Assessment of life quality on Day 0 and 2 months after completing treatment
Detection of gut microbiota	use cecal stool DNA purification and quantification of cecal microbiota by quantitative PCR (qPCR). Using V3-V5 16S rRNA amplification; Processing of NGS data; Operational Taxonomic Units (OTUs) cluster; Taxonomic profiling	Assessment of gut microbiota on Day 0 and 2 months after completing treatment
Change in serum total and mite specific IgE	check serum total IgE and mite specific IgE (KIU/l)	Assessment of serologic markers on Day 0 and 2 months after completing treatment
T Cells measurement	check CD4 / CD8 by flowcytometry	Assessment of CD4/CD8 on Day 0 and 2 months after completing treatment
Measurement of cytokines produced by polymorphonuclear leukocytes	check sICAM-1,IL-8,PGE2, LTC4	Assessment of serologic markers on Day 0 and 2 months after completing treatment
Measurement of cytokines produced by monocytes and lymphocytes	IL-4、IL-5、IL-10、IL-13、IFN-γ	Assessment of serologic markers on Day 0 and 2 months after completing treatment
Detection of dendritic cell function	check IL-10 and IL-12 level	Assessment of serologic markers on Day 0 and 2 months after completing treatment

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Investigators: Study Director: Sien-hung Yang, Ph.D., Chang Gung Memorial Hospital, Taoyuan, Taiwan

Publications and helpful links

General Publications

• Yang SH, Hong CY, Yu CL. Decreased serum IgE level, decreased IFN-gamma and IL-5 but increased IL-10 production, and suppressed cyclooxygenase 2 mRNA expression in patients with perennial allergic rhinitis after treatment with a new mixed formula of Chinese herbs. Int Immunopharmacol. 2001 Jun;1(6):1173-82. doi: 10.1016/s1567-5769(01)00051-0.
• Yang SH, Hong CY, Yu CL. The stimulatory effects of nasal discharge from patients with perennial allergic rhinitis on normal human neutrophils are normalized after treatment with a new mixed formula of Chinese herbs. Int Immunopharmacol. 2002 Nov;2(12):1627-39. doi: 10.1016/s1567-5769(02)00133-9.
• Yang SH, Yu CL, Chen YL, Chiao SL, Chen ML. Traditional Chinese medicine, Xin-yi-san, reduces nasal symptoms of patients with perennial allergic rhinitis by its diverse immunomodulatory effects. Int Immunopharmacol. 2010 Aug;10(8):951-8. doi: 10.1016/j.intimp.2010.05.008. Epub 2010 May 28.
• Hwang BF, Jaakkola JJ, Lee YL, Lin YC, Guo YL. Relation between air pollution and allergic rhinitis in Taiwanese schoolchildren. Respir Res. 2006 Feb 9;7(1):23. doi: 10.1186/1465-9921-7-23.
• Kuroiwa A, Liou S, Yan H, Eshita A, Naitoh S, Nagayama A. Effect of a traditional Japanese herbal medicine, hochu-ekki-to (Bu-Zhong-Yi-Qi Tang), on immunity in elderly persons. Int Immunopharmacol. 2004 Feb;4(2):317-24. doi: 10.1016/j.intimp.2003.12.004.
• Yang SH, Kao TI, Chiang BL, Chen HY, Chen KH, Chen JL. Immune-modulatory effects of bu-zhong-yi-qi-tang in ovalbumin-induced murine model of allergic asthma. PLoS One. 2015 Jun 2;10(6):e0127636. doi: 10.1371/journal.pone.0127636. eCollection 2015.
• Xie MQ, Liu J, Long Z, Tian DF, Zhao CQ, Yang PC. Modulation of immune tolerance with a Chinese traditional prescription inhibits allergic rhinitis in mice. N Am J Med Sci. 2011 Nov;3(11):503-7. doi: 10.4297/najms.2011.3503.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2018
• Primary Completion (Anticipated): July 31, 2020
• Study Completion (Anticipated): July 31, 2020

Study Registration Dates

• First Submitted: May 31, 2016
• First Submitted That Met QC Criteria: January 24, 2017
• First Posted (Estimate): January 26, 2017

Study Record Updates

• Last Update Posted (Actual): January 26, 2018
• Last Update Submitted That Met QC Criteria: January 24, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: gut microbiota; Qi-tonifying regimen; immune-modulation
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Otorhinolaryngologic Diseases; Respiratory Hypersensitivity; Hypersensitivity; Nose Diseases; Rhinitis; Rhinitis, Allergic
• Other Study ID Numbers: CORPG1F0011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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