Evaluating the Effects of Traditional Chinese Medicine by N-of-1 Trials

Shanghai University of Traditional Chinese Medicine36 enrolled

Overview

Treatment based on syndrome differentiation is the essence of traditional Chinese Medicine(TCM) and forms the individualized treatment. N-of-1 trials may be a good clinical effect evaluation method for the individualized treatment of TCM. This study aims to compare: (1) the efficacy of syndrome differentiation(individualized decoction) with placebo, (2)the efficacy of syndrome differentiation(individualized decoction) with the same prescription minus heat-clearing Chinese herbs, for patients with stable bronchiectasis through N-of-1 trials.

Traditional Chinese medicine is one of the important part of complementary and alternative medicine in the world, and it plays increasingly important role in the international medical practice. Treatment based on syndrome differentiation is the essence of traditional Chinese Medicine (TCM) and forms the individualized treatment. However, this individualized TCM intervention often makes it difficult for population-based RCTs to carry out a standard form. N-of-1 trials may be a good clinical effect evaluation method for the individualized treatment of TCM. The key hypothesis of this study is that: (1) the efficacy of syndrome differentiation(individualized decoction) will be better than placebo in patients with stable bronchiectasis through N-of-1 trials. (2) the efficacy of syndrome differentiation(individualized decoction) will be better than the same prescription minus heat-clearing Chinese herbs in patients with stable bronchiectasis through N-of-1 trials. The difference of efficacy may be various according to the individual severity of phlegm-heat. In this study, We will conduct a single center N-of-1 trials in 36 patients with stable bronchiectasis without hemoptysis and respiratory failure. These N-of-1 trials will be 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. We will compare :(1) the efficacy of syndrome differentiation(individualized decoction) with placebo, (2) the efficacy of syndrome differentiation(individualized decoction) with the same prescription minus heat-clearing Chinese herbs, in patients with stable bronchiectasis through N-of-1 trials. The primary outcome is patient self-reported symptoms(such as cough, expectoration, shortness of breath, chest pain, and fatigue) scores on a 7 point visual analogue scale. Secondary outcomes are 24-hour sputum volume and CAT（The COPD Assessment Test） scores. We use paired t test for single case. Mixed effects model taking account of "Carryover Effects" and meta-analysis will be used for a series of N-of-1 trials as a group.

Interventions

Individualized DecoctionDRUG

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

placeboDRUG

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.

Tested drug minus heat-clearing herbsDRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * the diagnostic criteria based on the consensus of Chinese experts and the guidelines for noncystic fibrosis bronchiectasis issued by the British Thoracic Society in 2010; * 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. Exclusion Criteria: * 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,and kidney dysfunctions; * participating in other pharmacological clinical trials within the past 3 months.

Outcomes

Primary Outcomes

Patient Self-Rated Symptom Score

Patients rated the severity of the symptoms (such as cough, expectoration, shortness of breath, chest pain, and fatigue) on a 7 point visual analogue scales. The higher the score, the more severe the symptom.

Time frame: 4 weeks

Secondary Outcomes

24 h Sputum Volume

We measured the 24h sputum volume at the beginning and the end of each treatment period of the trial. To ensure the accuracy of the measurement, we asked the patients to spit sputum into a collector with scales from 8:00 am to the next 8:00 am. We used the mean value of the sputum volume for 3 consecutive days as the outcome.