A Series of N-of-1 Trials of Traditional Chinese Medicine Based on Bayesian Method

NCT04601792 | Unknown Phase 4

• 1 other identifier: haiyin huang
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

The guiding role of parallel randomized controlled trials in clinical practice is limited due to the insufficiency of individual information. Our previous studies showed that Single case randomized controlled trials (referred to as N-of-1 trials) could reflect the individualized characteristics of traditional Chinese medicine (TCM) syndrome differentiation with good feasibility, but the sensitivity was low. This study aims to compare the efficacy of treatment based on syndrome differentiation with controlled decoctions (placebo, and the method of strengthening the body resistance and removing phlegm) among patients with stable bronchiectasis through a series of N-of-1 trials (single-patient, double-blind, randomized, multiple crossover design), with the 7 point-likert scale of the most concerned symptoms as the main outcome. Hierarchical Bayesian statistical methods and some parameters and variables will be introduced, such as TCM syndrome type, potential residue effect of TCM, etc. The sensitivity and applicability of various mathematical models (Hierarchical Bayesian, paired t-test and Meta-analysis) for N-of-1 trials of TCM will be tested, for the purpose of improving the sensitivity and applicability of N-of-1 trials of TCM both on individual and group levels.

Conditions

Bronchiectasis; Quality of Life; Traditional Chinese Medicine; Sputum; Symptoms; Individuality

Keywords

N-of-1 trials; Drugs, Chinese Herbal; symptoms; individualized treatment; stable bronchiectasis; Bayesian

Outcome Measures

Primary Outcomes (1)

• Patient Self-Rated Symptom Score (likert scale)

  Patients rated the severity of the symptoms (such as cough, expectoration, shortness of breath and chest pain) on a 7 point likert scale. Optimize the number of questions to ensure that the most important aspects of the patient's problem are detected (usually four to eight items). Every day each patient scored the severity of these problems on the 7 point Likert scales supplemented by Visual Analogue Scales (VAS). The higher the score, the more severe the symptom. The investigators consider an improvement of 0.5 points per question corresponds to a noticeable improvement in the patient's well-being. If there are seven questions, a total change of 3.5 or more points is considered clinically significant. Thus the mean difference of 0.5 points was defined as the "Minimal Clinically Important Difference (MCID)" for the 7 point scales.

  4 weeks

Secondary Outcomes (2)

• 24 hours sputum volume

  4 weeks

• COPD Assessment Test (CAT)

  4 weeks

Other Outcomes (4)

• Treatment preference for TCM

  Through study completion, an average of half a year

• Change in of the alanine aminotransferase (ALT), to evaluate the safety of TCM treatment

  Baseline and month 6

• Change in of the blood urea nitrogen (BUN), to evaluate the safety of TCM treatment

  Baseline and month 6

Study Arms (3)

Individualized Decoction

EXPERIMENTAL

It is the highly individualized treatment of TCM, the modification of Bronchiectasis Stabilization Decoction (Rhizoma Fagopyri Cymosi 30g, Radix Lithospermi 15g, Radix Ophiopogonis 15g, Poria cocos 15g, Radix Astragali 20g, Rhizoma Bletillae 10g, Platycodon grandiflorum 10g, Semen Coicis 30g) based on syndrome differentiation. For subjects with lung and spleen qi deficiency syndrome, the investigators added Radix Codonopsis Pilosulae, Pericarpium Citri Reticulatae, and Atractylodes Macrocephala Koidz. The investigators can adjust the individualized decoction in accordance with the change in the patient's condition throughout the whole study duration. The Chinese herbal decoction is taken by one decoction a day and divided into 2 doses, for 3 weeks in each observation period.

Drug: Individualized Decoction; Drug: placebo; Drug: Tested drug minus heat-clearing herbs

placebo

PLACEBO COMPARATOR

Placebo is made by dextrin, bitter agent, edible pigment etc. and added 5% test drug. The placebo and test drug have no differences in dosage form, appearance, color, specification, label, and so forth. The placebo is taken by one decoction a day and divided into 2 doses, for 3 weeks in each observation period.

Drug: Individualized Decoction; Drug: placebo

Tested drug minus heat-clearing herbs

ACTIVE COMPARATOR

It is the decoction of the Individualized Syndrome Differentiation Decoction (tested drug) minus heat-clearing herbs. For example, heat-clearing herbs such as Scutellaria Baicalensis, Rhizoma Coptidisor Herba Violae will be removed from the Syndrome Differentiation Decoction. This control Chinese herbal decoction is taken by one decoction a day and divided into 2 doses, for 3 weeks in each observation period.

Drug: Individualized Decoction; Drug: Tested drug minus heat-clearing herbs

Interventions

Individualized Decoction DRUG

Applied in the Tested Drug Observation Period. It is the highly individualized treatment of TCM, the modification of Bronchiectasis Stabilization Decoction (Rhizoma Fagopyri Cymosi 30g, Radix Lithospermi 15g, Radix Ophiopogonis 15g, Poria cocos 15g, Radix Astragali 20g, Rhizoma Bletillae 10g, Platycodon grandiflorum 10g, Semen Coicis 30g) based on syndrome differentiation. For example, for patients with qi and yin deficiency syndrome, the investigators added Adenophora Root, Radix Glehniae and Radix Rehmanniae Recens etc. For patients with phlegm-heat syndrome, the investigators added Radix Scutellariae and Viola Yedoensis etc. Besides, the herbs in a prescription could be changed according to different symptoms of individual patients.

Also known as: Syndrome Differentiation Decoction

Individualized Decoction; Tested drug minus heat-clearing herbs; placebo

placebo DRUG

Applied in the placebo Observation Period. Placebo is made by dextrin, bitter agent, edible pigment etc. and added 5% test drug. The test drug and control drug have no differences in dosage form, appearance, color, specification, label, and so forth.

Individualized Decoction; placebo

Tested drug minus heat-clearing herbs DRUG

It is the decoction of the Syndrome Differentiation Decoction (tested drug) minus heat-clearing herbs. For example, heat-clearing herbs such as Scutellaria Baicalensis, Rhizoma Coptidisor Herba Violae will be removed from the Syndrome Differentiation Decoction.

Individualized Decoction; Tested drug minus heat-clearing herbs

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• according to the consensus of domestic experts, combined with the guidelines for the management of adult bronchiectasis published by the European Respiratory Society in 2017;
• male or female, aged 18-70 years;
• being in the stable stage, and no acute exacerbation of bronchiectasis within the past three weeks;
• frequency of acute exacerbation of bronchiectasis ≤3 times every year;
• signed informed consent for participation.

You may not qualify if:

• having developed respiratory failure with estimated survival time less than one year;
• having hemoptysis as a comorbidity;
• having complications by active tuberculosis;
• being pregnant or with severe heart, liver, or kidney dysfunctions;
• participating in other pharmacological clinical trials within the past 3 months.

Sponsors & Collaborators

• Shanghai University of Traditional Chinese Medicine: lead
• Guangzhou University of Traditional Chinese Medicine: collaborator

Study Sites (1)

Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine

Shanghai, 200437, China

RECRUITING

Related Publications (7)

• Huang H, Yang P, Wang J, Wu Y, Zi S, Tang J, Wang Z, Ma Y, Zhang Y. Investigation into the Individualized Treatment of Traditional Chinese Medicine through a Series of N-of-1 Trials. Evid Based Complement Alternat Med. 2018 Feb 7;2018:5813767. doi: 10.1155/2018/5813767. eCollection 2018.

  PMID: 29552084 RESULT

• Huang H, Yang P, Xue J, Tang J, Ding L, Ma Y, Wang J, Guyatt GH, Vanniyasingam T, Zhang Y. Evaluating the Individualized Treatment of Traditional Chinese Medicine: A Pilot Study of N-of-1 Trials. Evid Based Complement Alternat Med. 2014;2014:148730. doi: 10.1155/2014/148730. Epub 2014 Nov 11.

  PMID: 25477988 RESULT

• Lee BY, Lee S, Lee JS, Song JW, Lee SD, Jang SH, Jung KS, Hwang YI, Oh YM. Validity and Reliability of CAT and Dyspnea-12 in Bronchiectasis and Tuberculous Destroyed Lung. Tuberc Respir Dis (Seoul). 2012 Jun;72(6):467-74. doi: 10.4046/trd.2012.72.6.467. Epub 2012 Jun 29.

  PMID: 23101012 RESULT

• Guyatt G，Rennie D. Users'Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice[M].Chicago: American Medical Association Press，2002:3-11.

  RESULT

• Dodd JW, Hogg L, Nolan J, Jefford H, Grant A, Lord VM, Falzon C, Garrod R, Lee C, Polkey MI, Jones PW, Man WD, Hopkinson NS. The COPD assessment test (CAT): response to pulmonary rehabilitation. A multicentre, prospective study. Thorax. 2011 May;66(5):425-9. doi: 10.1136/thx.2010.156372. Epub 2011 Mar 12.

  PMID: 21398686 RESULT

• Jones PW, Price D, van der Molen T. Role of clinical questionnaires in optimizing everyday care of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2011;6:289-96. doi: 10.2147/COPD.S18181. Epub 2011 May 26.

  PMID: 21697993 RESULT

• Lu L, An J, Chen H, Yang P, Xu M, Wu Y, Wang Z, Shen L, Chen X, Huang H. A Series of N-of-1 Trials for Traditional Chinese Medicine Using a Bayesian Method: Study Rationale and Protocol. Evid Based Complement Alternat Med. 2021 Apr 17;2021:9976770. doi: 10.1155/2021/9976770. eCollection 2021.

  PMID: 34122611 DERIVED

MeSH Terms

Conditions

Bronchiectasis

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases

Central Study Contacts

Haiyin Huang, M.D.

CONTACT

008602165161782; huanghaiyin@shyueyanghospital.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo is made by dextrin, bitter agent, edible pigment etc and added 5% test drug. The test drug and control drug have no differences in dosage form, appearance, color, specification, label, and so forth.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: randomized, double-blind, crossover comparisons of individualized herbal decoction with control decoction within individual patients. Each N-of-1 trial has 3 pairs of treatment periods. The duration of each treatment period will be 4 weeks.

Study Record Dates

• First Submitted: August 24, 2020
• First Posted: October 26, 2020
• Study Start: December 1, 2019
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2022
• Last Updated: October 26, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The data will become available when the investigators finish the study and last for 5 years.
• Access Criteria: available to researchers around the world upon request.

Locations

CN (1)