Effects of a Mixed Chinese Herbal Formula on Atopic Dermatitis

Evaluation of Clinical Efficacy and Pharmacological Mechanism of a Mixed Chinese Herbal Formula in Atopic Dermatitis Patients by Integrating Metabolomics and Pharmacokinetic Analysis

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.

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

1. D: Safety evaluation by measuring side effects, hemogram, electrolytes, kidney and liver function Aim 2: Effects of a mixed CHF on gut microbiota in AD patients
2. A: Fecal DNA purification and 16S rRNA gene sequencing before and after CHF treatment

2B: Bioinformatics analysis to explore microbial dysfunction underlying AD and changes of gut microbiome after CHF treatment 2C: Determination of short-chain fatty acid (SCFA) levels in fecal samples before and after CHF treatment Aim 3: Effects of a mixed CHF on plasma metabolomes of AD patients 3A: Plasma metabolomics analysis in AD patients with different TCM patterns 3B: Plasma metabolomics analysis in AD patients under a mixed CHF treatment 3C: Determination of the previously known immunomodulatory metabolites in AD patients under a mixed CHF treatment Aim 4: PK study between healthy volunteers, valid patients, and patients with poor response to the mixed CHF 4A: Preparation and quality control of target prescription 4B: PK study of the mixed CHF

Inclusion Criteria:

1. All volunteers must sign an informed consent form.
2. Male and female patients aged 6 to 60 years.
3. 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.
4. SCORing Atopic Dermatitis (SCORAD) score ≧ 25

Exclusion Criteria:

1. Other skin diseases that are not AD, such as contact dermatitis, seborrheic dermatitis, or drug-induced dermatitis, which will be diagnosed by expert clinicians
2. Patients with other itching skin diseases at the same time, diagnosed by expert clinicians
3. 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
4. Patients who cannot take the medicine regularly, or who can not cooperate in writing the questionnaires or taking blood tests
5. Allergy to Chinese medicine or use of other Chinese medicine treatments
6. 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
7. Uncontrolled psychiatric problems or other severe systemic diseases
8. Current pregnant or breast-feeding women, and all women of childbearing age must agree to take appropriate contraceptive precautions