Lung Dispersing, Turbid Descending and Gut Clearing Decoction for Bronchiectasis (LUNG-CLEAR)

Efficacy and Safety of Lung Dispersing, Turbid Descending and Gut Clearing Decoction on Clinically Stable Bronchiectasis (LUNG-CLEAR): A Multicenter, Randomized, Cross-over Trial

Bronchiectasis is a chronic airway disease which confers significant healthcare burden, with limited therapeutic approaches. From the perspective of traditional Chinese medicine, congenital insufficiency of the lung, spleen and kidney, when coupled with external injury or mood impairment, may collectively contribute to bronchiectasis pathogenesis due to heat trapping in the phlems, congestion of wind evils and stagnation of blood. Here, the investigators will explore the Lung Dispersing, Turbid Descending and Gut Clearing Decoction (LTGD) which targets at expelling the wind evil in patients with bronchiectasis. The investigators sought to conduct a multicenter, randomized cross-over trial which investigates the efficacy and safety of LTGD on clinically stable bronchiectasis.

Study Overview

• Status: Not yet recruiting
• Conditions: Quality of Life; Bronchiectasis Adult; Traditional Chinese Medicine; Exacerbation
• Intervention / Treatment: Combination product: Traditional Chinese Medicine (TCM)

Detailed Description

Bronchiectasis is a chronic airway disease which confers significant healthcare burden, with limited therapeutic approaches. From the perspective of traditional Chinese medicine, congenital insufficiency of the lung, spleen and kidney, when coupled with external injury or mood impairment, may collectively contribute to bronchiectasis pathogenesis due to heat trapping in the phlems, congestion of wind evils and stagnation of blood. Symptomatic treatment may be effective and safe for ameliorating respiratory symptoms and hindering disease progression of bronchiectasis. Here, the investigators have explored the Lung Dispersing, Turbid Descending and Gut Clearing Decoction (LTGD) which targets at expelling the wind evil in patients with bronchiectasis. The investigators sought to conduct a multicenter, randomized cross-over trial which investigates the efficacy and safety of LTGD on clinically stable bronchiectasis.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zhi-min Zhang, M.D.; Phone Number: +86-18928868345; Email: zhangzhimin51666@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• aged between 18 and 75 years;
• remained clinically stable (respiratory symptoms and lung function parameters not exceeding normal daily variations) for 4 consecutive weeks;
• no acute upper respiratory tract infections within 4 weeks;
• 1 or more BEs within the previous 2 years

Exclusion Criteria:

• Other unstable concomitant systemic illnesses (i.e. coronary heart disease, recent cerebral stroke, severe uncontrolled hypertension, active gastric or duodenal ulcer, uncontrolled diabetes, malignancy, hepatic or renal dysfunction);
• Concomitant asthma, allergic bronchopulmonary aspergillosis, or active tuberculosis;
• Concomitant chronic obstructive pulmonary disease as the predominant diagnosis;
• Treatment with inhaled, oral or systemic antibiotics within 4 weeks;
• Type 2 respiratory failure needing oxygen therapy or non-invasive mechanical ventilation;
• Females during lactation or pregnancy;
• Poor understanding or failure to properly operate the instrument;
• Participation in other clinical trials within 3 months.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Usual treatment; oral mucolytics [ambroxol 30mg tid, or N-acetylcysteine 0.2g tid, serrapeptase 10mg tid, or carbocisteine 500mg tid]	Combination product: Traditional Chinese Medicine (TCM); Traditional Chinese Medicine plus oral mucolytics [ambroxol 30mg tid, or N-acetylcysteine 0.2g tid, serrapeptase 10mg tid, or carbocisteine 500mg tid]; Agastache rugosus 5g, Scutellaria baicalensis 10g, Radix Puerariae 10g, Acorus tatarinowii schott 10g, Fructus Liquidambaris 5g, gypsum 15 g, Rheum officinale 5 g, Folium sennae 5 g, Codonopsis pilosula 10g, Radix Salviae Miltiorrhizae 10g, Lignum millettiae 10 g, Liquiritia glycyrrhiza 10 g Optional formulae: bile arisaema 15g, polygala tenuifolia 15g, Mangnolia officinalis 10g, Fructus aurantii immaturus 10g; Magnetite 15-30g and reddle15-30g; Other Names: TCM
Active Comparator: TCM treatment; Traditional Chinese Medicine plus oral mucolytics (described above); Agastache rugosus 5g, Scutellaria baicalensis 10g, Radix Puerariae 10g, Acorus tatarinowii schott 10g, Fructus Liquidambaris 5g, gypsum 15 g, Rheum officinale 5 g, Folium sennae 5 g, Codonopsis pilosula 10g, Radix Salviae Miltiorrhizae 10g, Lignum millettiae 10 g, Liquiritia glycyrrhiza 10 g	Combination product: Traditional Chinese Medicine (TCM); Traditional Chinese Medicine plus oral mucolytics [ambroxol 30mg tid, or N-acetylcysteine 0.2g tid, serrapeptase 10mg tid, or carbocisteine 500mg tid]; Agastache rugosus 5g, Scutellaria baicalensis 10g, Radix Puerariae 10g, Acorus tatarinowii schott 10g, Fructus Liquidambaris 5g, gypsum 15 g, Rheum officinale 5 g, Folium sennae 5 g, Codonopsis pilosula 10g, Radix Salviae Miltiorrhizae 10g, Lignum millettiae 10 g, Liquiritia glycyrrhiza 10 g Optional formulae: bile arisaema 15g, polygala tenuifolia 15g, Mangnolia officinalis 10g, Fructus aurantii immaturus 10g; Magnetite 15-30g and reddle15-30g; Other Names: TCM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Bronchiectasis Health Questionnaire scores at month 6 compared with baseline	Changes in Bronchiectasis Health Questionnaire scores at month 6 compared with baseline	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the frequency of bronchiectasis exacerbation	the frequency of bronchiectasis exacerbation	6 months
the time to the first bronchiectasis exacerbation	the time to the first bronchiectasis exacerbation	6 months
changes in forced expiratory volume in one second at month 6 compared with baseline	changes in forced expiratory volume in one second at month 6 compared with baseline	6 months
24-hour sputum volume at month 6 compared with baseline	24-hour sputum volume at month 6 compared with baseline	6 months
changes in sputum purulence score at month 6 compared with baseline	changes in sputum purulence score at month 6 compared with baseline	6 months
the proportion of patients isolated with Pseudomonas aeruginosa at month 6 compared with baseline	the proportion of patients isolated with Pseudomonas aeruginosa at month 6 compared with baseline	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in sputum hydrogen peroxide level at month 6 compared with baseline	changes in sputum hydrogen peroxide level at month 6 compared with baseline	6 months
changes in sputum catalase activity at month 6 compared with baseline	changes in sputum catalase activity at month 6 compared with baseline	6 months
changes in sputum total antioxidant capacity at month 6 compared with baseline	changes in sputum total antioxidant capacity at month 6 compared with baseline	6 months
changes in airway resistance measured at 5 Hz at month 6 compared with baseline	changes in airway resistance measured at 5 Hz at month 6 compared with baseline	6 months
changes in Quality-of-life-bronchiectasis questionnaire score at month 6 compared with baseline	changes in Quality-of-life-bronchiectasis questionnaire score at month 6 compared with baseline	6 months
changes in sputum microbiota composition at month 6 compared with baseline	changes in sputum microbiota composition at month 6 compared with baseline	6 months
Changes in AX at month 6 compared with baseline	Changes in AX at month 6 compared with baseline	6 months
Changes in sputum superoxide dismutase activity at month 6 compared with baseline	Changes in sputum superoxide dismutase activity at month 6 compared with baseline	6 months

Collaborators and Investigators

• Sponsor: Guangzhou Institute of Respiratory Disease
• Collaborators: Guangdong Provincial Hospital of Traditional Chinese Medicine
• Investigators: Study Chair: Wei-jie Guan, MD, First Affiliated Hospital of Guangzhou Medical University

Publications and helpful links

General Publications

• Pasteur MC, Bilton D, Hill AT; British Thoracic Society Non-CF Bronchiectasis Guideline Group. British Thoracic Society guideline for non-CF bronchiectasis. Thorax. 2010 Jul;65(7):577. doi: 10.1136/thx.2010.142778. No abstract available.
• Loukides S, Horvath I, Wodehouse T, Cole PJ, Barnes PJ. Elevated levels of expired breath hydrogen peroxide in bronchiectasis. Am J Respir Crit Care Med. 1998 Sep;158(3):991-4. doi: 10.1164/ajrccm.158.3.9710031.
• Horvath I, Loukides S, Wodehouse T, Kharitonov SA, Cole PJ, Barnes PJ. Increased levels of exhaled carbon monoxide in bronchiectasis: a new marker of oxidative stress. Thorax. 1998 Oct;53(10):867-70. doi: 10.1136/thx.53.10.867.
• Tsang KW, Chan K, Ho P, Zheng L, Ooi GC, Ho JC, Lam W. Sputum elastase in steady-state bronchiectasis. Chest. 2000 Feb;117(2):420-6. doi: 10.1378/chest.117.2.420.
• Quittner AL, O'Donnell AE, Salathe MA, Lewis SA, Li X, Montgomery AB, O'Riordan TG, Barker AF. Quality of Life Questionnaire-Bronchiectasis: final psychometric analyses and determination of minimal important difference scores. Thorax. 2015 Jan;70(1):12-20. doi: 10.1136/thoraxjnl-2014-205918. Epub 2014 Oct 16.
• Spinou A, Siegert RJ, Guan WJ, Patel AS, Gosker HR, Lee KK, Elston C, Loebinger MR, Wilson R, Garrod R, Birring SS. The development and validation of the Bronchiectasis Health Questionnaire. Eur Respir J. 2017 May 11;49(5):1601532. doi: 10.1183/13993003.01532-2016. Print 2017 May.
• Zheng J, Zhong N. Normative values of pulmonary function testing in Chinese adults. Chin Med J (Engl). 2002 Jan;115(1):50-4.
• Guan WJ, Gao YH, Xu G, Lin ZY, Tang Y, Li HM, Lin ZM, Zheng JP, Chen RC, Zhong NS. Sputum bacteriology in steady-state bronchiectasis in Guangzhou, China. Int J Tuberc Lung Dis. 2015 May;19(5):610-9. doi: 10.5588/ijtld.14.0613.
• Guan WJ, Gao YH, Xu G, Lin ZY, Tang Y, Gu YY, Liu GH, Li HM, Chen RC, Zhong NS. Sputum matrix metalloproteinase-8 and -9 and tissue inhibitor of metalloproteinase-1 in bronchiectasis: clinical correlates and prognostic implications. Respirology. 2015 Oct;20(7):1073-81. doi: 10.1111/resp.12582. Epub 2015 Jun 30.
• Zhang ZM, Ren PH, Wu ZJ, Zhang DP, Xie WJ. Personalized alternative therapy of intractable bronchiectasis-induced hemoptysis in a patient: syndrome differentiation and treatment according to individual physique category. J Thorac Dis. 2013 Jun;5(3):E115-7. doi: 10.3978/j.issn.2072-1439.2013.06.26. No abstract available.
• Guan WJ, Gao YH, Xu G, Lin ZY, Tang Y, Li HM, Lin ZM, Zheng JP, Chen RC, Zhong NS. Impulse oscillometry in adults with bronchiectasis. Ann Am Thorac Soc. 2015 May;12(5):657-65. doi: 10.1513/AnnalsATS.201406-280OC.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 31, 2021
• Primary Completion (Anticipated): August 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: June 4, 2017
• First Submitted That Met QC Criteria: June 4, 2017
• First Posted (Actual): June 6, 2017

Study Record Updates

• Last Update Posted (Actual): February 11, 2020
• Last Update Submitted That Met QC Criteria: February 8, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchiectasis
• Other Study ID Numbers: GWJ-TCM-2017

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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