Clinical trial NCT05045469
Conditions: Rosacea Chinese Herbal Medicine
Sponsor: Chang Gung Memorial Hospital
Start date: 2021-08-04; Completion date: 2024-08-04
Enrollment: 24 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The aim of this study is to investigate the effects of topical herbal medicine in the patients with rosacea.

Detailed description:
Rosacea is a chronic inflammatory disorder which affects the cheek, nose, chin, forehead and eyes. It is typically characterized by cutaneous signs such as flushing, erythema, telangiectasia, papules, and pustules in the face. The pathogenic mechanism of rosacea is unknown, and there is no cure for rosacea. The therapeutic approaches include oral medicine, topical medicine and surgical interventions depending on the different subtypes of rosacea. The recent study demonstrates that combination therapy may be more effectively improved the symptoms of rosacea. Dian dao san is a topical herbal compound for reducing the features as flushing, erythema, papules, and pustules for years. The investigators hypothesize that dian dao san can be more beneficial in treating the patients with rosacea and improving the quality of life.

Arms: arm 1: Herbal medicine (dian dao san) will be applied to the lesions of rosacea twice a day. Subject will receive persistent treatment for 6 weeks. arm 2: Placebo (topical medicine without therapeutic effects) will be applied to the lesions of rosacea twice a day. Subject will receive persistent treatment for 6 weeks.
Interventions: intervention 1: dian dao san
Intervention descriptions: intervention 1: dian dao san and placebo will be used in the rosacea lesions twice a day for 6 weeks

Protocol documents:
Prot_SAP_000.pdf: 
Therapeutic Effects of Topical Herbal Medicine -Rhubarb Ointment 
on Rosacea 
NCT number: NCT05045469 
document date:2025/03/12 
 
Study Aims 
A review of the literature reveals that clinical studies on topical botanical and 
traditional Chinese herbal medicine (TCM) for rosacea are limited. A 2012 study 
published in The Journal of Clinical Pharmacology reported that Quassia extract 
significantly improved erythema, flushing, papules, and vascular proliferation in 
rosacea patients. Additionally, a 2005 randomized trial published in the European 
Academy of Dermatology and Venereology demonstrated that chrysanthemum extract 
was more effective than the control group in reducing erythema area and severity. 
Currently, the optimal treatment for rosacea remains unclear, and research on the 
therapeutic effects of topical Chinese herbal medicine for rosacea is scarce. According 
to the Qing Dynasty medical classic Yi Zong Jin Jian, the Diandao San formula, 
which contain rhubarb is traditionally used to clear heat, eliminate parasites, detoxify, 
cool the blood, and promote blood circulation, making it suitable for treating 
conditions such as erythema, acne, and folliculitis, which align with rosacea 
symptoms. 
Recent studies also suggest that combination therapy is beneficial in treating rosacea. 
Therefore, this study aims to evaluate the efficacy of this TCM herbal formula in the 
treatment of rosacea. 
IRB number: 202101000A3 
Study Design 
Patients were enrolled in the study following assessment by dermatologists or 
traditional Chinese medicine (TCM) practitioners, ensuring they met the inclusion and 
exclusion criteria. 


Inclusion Criteria: 
• 
Patients aged 20 years or older diagnosed with rosacea. 
• 
Willing to sign a written informed consent form and comply with medical 
guidance. 
• 
No use of any medication for rosacea treatment within the past two weeks. 
Exclusion Criteria: 
• 
History of malignant skin tumors at the rosacea-affected site. 
• 
High risk of skin infection at the affected site. 
• 
History of allergic reactions to topical herbal medicines. 
• 
Pregnant individuals. 
• 
Inability to complete study questionnaires or comply with medical 
instructions. 
The study enrolled 24 participants from two sites: Keelung Hospital and Lover’s Lake 
Hospital. Participants were randomly assigned into two groups via computer-
generated randomization, with 12 individuals in the experimental group and 12 in the 
control group. The experimental group received Diandao San ointment, while the 
control group received a placebo ointment with a similar appearance and scent but 
without therapeutic effects. Both ointments were applied twice daily to clean skin on 
the affected areas for six weeks. In cases of adverse skin reactions, application was 
temporarily halted, and the reactions were documented and monitored. 
Assessment and Evaluation 
Before enrollment, participants underwent evaluations, including Fitzpatrick skin type 
classification, distribution of rosacea lesions, severity of erythema, papules, and 
pustules, and quality of life assessments. Adverse skin reactions were also recorded. 
Follow-up assessments were conducted at weeks 1, 2, 4, and 6 by TCM practitioners, 
who re-evaluated skin symptoms, quality of life, and adverse reactions. 
• 
Skin Type: Assessed using the Fitzpatrick classification scale. 
• 
Lesion Distribution: Documented with photographs, noting affected areas 
such as bilateral cheeks, nose, chin, forehead, and eyes. 
• 
Severity of Skin Symptoms: Assessed using the Investigator Global 
Assessment (IGA) scale. 
• 
Quality of Life: Measured using the Dermatology Quality of Life Index 
(DQoL), evaluating emotional, symptomatic, and lifestyle impacts. 


Participants in the experimental group achieving an IGA and DQoL score of 0-1 after 
six weeks were considered to have significant improvement and did not require 
further treatment. Those with IGA scores of 2-3 or DQoL scores between 2-10, 
showing significant improvement compared to baseline, continued using Diandao San 
ointment. Participants with no significant improvement post-trial were referred to 
dermatologists and TCM practitioners for alternative treatment options. In the control 
group, participants experiencing severe adverse reactions, allergic responses, or 
infections were immediately withdrawn from the study and evaluated for further 
treatment. 
Data Analysis 
Statistical analysis was performed using SPSS software. Baseline differences were 
analyzed using ANOVA, while paired t-tests were used to compare pre- and post-
treatment data. The study assessed all parameters, including mean values and standard 
deviations, with a significance level set at α = 0.05 (one-tailed). 
The analysis uses Robust Linear Mixed-Effect Models (LMMs) due to the violation 
of normality in outcome measurements. To address this issue, robust LMM was 
applied to enhance the reliability of estimates by mitigating the effects of outliers or 
non-normal data distributions. 
Additionally, the robustlmm method was used, which down-weights outliers by 
modifying the loss function, ensuring that extreme observations do not 
disproportionately influence the fixed effect estimates. This approach increases the 
robustness of estimation methods, improving the accuracy and stability of the results.