Evaluation of Clinical Efficacy and Pharmacological Mechanism of a Mixed Chinese Herbal Formula in Atopic Dermatitis Patients by Integrating Metabolomics and Pharmacokinetic Analysis
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 120
- 主要终点
- Changes of SCORing Atopic Dermatitis (SCORAD) score after treatment with a mixed CHF (composed of Xiao-Feng-San + Zhen-Ren-Huo-Ming-Yin + Dictamnus dasycarpus + Houttuynia cordata)
研究概览
简要总结
The aim of this study is to investigate the clinical therapeutic effects of a mixed Chinese herbal formula (CHF) in treating atopic dermatitis (AD) based on its effects on cytokine levels and immune cell counts. Th1/Th2/Th17/Th22-related cytokines will be assayed to determine the mechanisms of the anti-inflammatory and immunomodulatory effects of the mixed CHF in AD patients. The nature of the microbiome dysfunction underlying this disease will be explored. Investigators will also apply a metabolomics approach to reveal the plasma metabolites in AD patients of different TCM patterns as well as to monitor changes of plasma metabolome in AD patients under mixed CHF treatment, aiming to develop metabolic biosignatures for efficacy of mixed CHF in AD patients exhibiting specific TCM pattern. PK study will be conducted to exam blood concentration of the prescription in healthy volunteers and AD patients with good or poor drug response. The results will provide evidence for the precision treatment based on different TCM pattens of AD patients. Completion of this integrated project will provide innovative information for future clinical applications.
详细描述
In this study, a randomized, double-blinded, placebo control trial is designed and total 120 AD patients will be enrolled. All participants will be divided into Chinese herbal formula (CHF) and placebo control groups, in 2:1 allocation ratio. CHF group will receive capsules of mixture CHF; while control group will receive placebo capsules with similar look, smell, and taste with same scheme. Total 12-week treatment course will be done.
Aim 1: The effects and immunomodulatory mechanisms of a mixed CHF in AD patients with different TCM patterns
1A: Measurement of AD severity by Scoring of AD (SCORAD) scale and assessment of health-related quality of life using the Dermatology Life Quality Index (DLQI) or Children's Dermatology Life Quality Index (CDLQI)
1B: Reduction rate of exposure to western medicine after a mixed CHF treatment
1C: The effects of CHF treatment on CRP, ESR, eosinophil count, IgE, CD4+/CD8+ and related cytokines / signaling pathway involved in AD regulation
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 6 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All volunteers must sign an informed consent form.
- •Male and female patients aged 6 to 60 years.
- •Patients who are diagnosed with AD by expert clinicians at Taoyuan, Linkou or Taipei Chang Gung Memorial Hospital and Taipei Veterans General Hospital in Taiwan and met the criteria of Hanifin and Rajka diagnostic criteria will be considered for enrollment in this study.
- •SCORing Atopic Dermatitis (SCORAD) score ≧ 25
排除标准
- •Other skin diseases that are not AD, such as contact dermatitis, seborrheic dermatitis, or drug-induced dermatitis, which will be diagnosed by expert clinicians
- •Patients with other itching skin diseases at the same time, diagnosed by expert clinicians
- •Patients who have secondary bacterial infections or receiving oral or intravenous steroid treatment, antibiotics, leukotriene modifiers, phototherapy or other immunosuppressive therapies in the previous 1 month
- •Patients who cannot take the medicine regularly, or who can not cooperate in writing the questionnaires or taking blood tests
- •Allergy to Chinese medicine or use of other Chinese medicine treatments
- •Severe organ dysfunction, such as impaired renal and hepatic function at initial diagnosis (including chronic kidney disease stages III, IV, and V and AST, ALT ≥3 × the upper normal limit), liver cirrhosis, or heart failure
- •Uncontrolled psychiatric problems or other severe systemic diseases
- •Current pregnant or breast-feeding women, and all women of childbearing age must agree to take appropriate contraceptive precautions
研究组 & 干预措施
Chinese herbal formula (CHF)
The patients in CHF group will take CHF capsules, 12 capsules (6 gm) twice a day, total 12 gm a day for 12 weeks, and the dosage will be modified according to patients' body weight. (3gm BID for 20kg≦BW<40kg; 1.5gm BID for BW<20kg)
干预措施: Chinese herbal formula (CHF) (Drug)
Control
The patients in control group will take the placebo capsules, which has the similar look, smell, and taste. The dosage, frequency, and duration are the same as CHF group, in which 12 capsules (6 gm) twice a day, total 12 gm a day for 12 weeks, and the dosage will be modified according to patients' body weight. (3gm BID for 20kg≦BW<40kg; 1.5gm BID for BW<20kg)
干预措施: Placebo (Drug)
结局指标
主要结局
Changes of SCORing Atopic Dermatitis (SCORAD) score after treatment with a mixed CHF (composed of Xiao-Feng-San + Zhen-Ren-Huo-Ming-Yin + Dictamnus dasycarpus + Houttuynia cordata)
时间窗: Assess at the beginning of the study and after 6 and 12 weeks' treatment, total 3 times
Measurement of symptoms related to AD including the severity of eczema, pruritis, and insomnia. The score ranges from 0 to 103 and higher scores mean a worse outcome.
Changes of exposure to western medicine by recording the name and dosage of western medicine used for AD treatment
时间窗: Assess at the beginning of the study, then weekly, up to 12 weeks
To explore whether the use of western medicine could be reduced after treatment with a mixed CHF
Changes of Dermatology Life Quality Index (DLQI) score (use Children's Dermatology Life Quality Index, CDLQI, for patients at the ages of 6 to 16 years) after treatment with a mixed CHF
时间窗: Assess at the beginning of the study and after 6 and 12 weeks' treatment, total 3 times
Measurement of quality of life.The score ranges from 0 to 30 and higher scores mean a worse outcome.
次要结局
- Compare blood concentration of mixed CHF between AD patients with different TCM patterns after a mixed CHF treatment by PK study(Assess at the beginning of the study and after 12 weeks' treatment, total 2 times)
- Concentration-time profile of mixed CHF between AD patients with different TCM patterns after a mixed CHF treatment by PK study(Assess at the beginning of the study and after 12 weeks' treatment, total 2 times)
- Changes of CRP level after a mixed CHF treatment(Assess at the beginning of the study and after 12 weeks' treatment, total 2 times)
- Changes of ESR level after a mixed CHF treatment(Assess at the beginning of the study and after 12 weeks' treatment, total 2 times)
- Changes of eosinophil count after a mixed CHF treatment(Assess at the beginning of the study and after 12 weeks' treatment, total 2 times)
- Changes of IgE level after a mixed CHF treatment(Assess at the beginning of the study and after 12 weeks' treatment, total 2 times)
- Changes of JAK1, JAK2, JAK3, tyrosine kinase-2 (TYK2), STAT1, STAT2, STAT3, STAT4, and STAT5 level after a mixed CHF treatment(Assess at the beginning of the study and after 12 weeks' treatment, total 2 times)
- Changes of CD4/CD8 ratio after a mixed CHF treatment(Assess at the beginning of the study and after 12 weeks' treatment, total 2 times)
- Changes of IL-4, IL-5, IL-10, IL-12, IL-13, IL-17, IL-22, IL-23, and INF-γ level after a mixed CHF treatment(Assess at the beginning of the study and after 12 weeks' treatment, total 2 times)
- Changes of gut microbiota(Assess at the beginning of the study and after 12 weeks' treatment, total 2 times)
- Differences in the AD-associated metabolites (phosphatidylcholine, acylcarnitine) between AD patients with different TCM patterns after a mixed CHF treatment(Assess at the beginning of the study and after 12 weeks' treatment, total 2 times)
- Differences in the anti-inflammatory metabolites (itaconate and its derivative, 4-octyl itaconate) between AD patients with different TCM patterns after a mixed CHF treatment(Assess at the beginning of the study and after 12 weeks' treatment, total 2 times)
研究者
YANG SIEN-HUNG
Professor
Chang Gung Memorial Hospital