中藥龜鹿二仙膠在健康族群的臨床不良反應評估

Adverse Events Assessment of Traditional Chinese Herbal Product, Guilu Erxian Jiao, in Healthy Volunteers

龜鹿二仙膠為臨床重要方劑，已有千年歷史，常用於退化性關節疾病與對抗老化，亦包含於台灣全民健保給付，然而，其安全性卻尚未經過臨床試驗檢驗。本試驗納入96 名健康受試者，隨機分配成四組，包含安慰劑與三種不同劑量的龜鹿二仙膠膠囊，分別為一天150 毫克、300 毫克與450 毫克，進行兩個月的隨機雙盲臨床試驗。期間以血相變化、肝腎功能變化、症狀問卷進行客觀與主觀的評估，並測試CD4+ 和CD8+T 淋巴球之個數與比例，監測對於免疫系統調節之影響。兩個月持續服用後，血相、肝腎功能方面並沒有明顯影響，症狀方面，口乾是唯一有意義的不良反應。CD4+T 淋巴球與CD4+/CD8+T 淋巴球之比例亦呈現有意義的變化；在較高劑量組（300 毫克/ 天與450 毫克/ 天），CD4+ 數目下降，且CD4+/CD8+ 比例反轉，此與其可用於治療退化性關節炎的機轉相關。龜鹿二仙膠在使用上需注意可能的口乾症狀，後續之療效試驗亦可續行於此安全性調查之結果。Guilu Erxian Jiao (GEJ) is a widely used herbal product for anti-aging and treatment of degenerative joint diseases. As drug adverse events of GEJ have not been well established, this paper was designed to assess adverse events of GEJ. 96 healthy volunteers were enrolled in this study, and a randomized, placebo-controlled, double-blind clinical trial was conducted. Adherence-to-protocol design was adopted to assess the precise side effects. Analysis on laboratory data of renal function, liver function, hematological changes, immunological parameters and questionnaires about possible adverse effects after two-month medical treatment were performed. In addition, another self-report of adverse events after taking GEJ was recorded. There were no clinically significant changes of biochemical indicators of liver function, renal function and hemogram. Ratio of CD4+ to CD8+ lymphocyte counts reversed in the subgroup of higher GEJ dosage (300mg/day and 450mg/day) which may explain the effectiveness of GEJ for osteoarthritis. In the analysis of the questionnaire, mouth dryness was the only one adverse event and its severity seemed not relevant to GEJ dosage. Further clinical trials can be designed based on the safety profile to evaluate the effectiveness of GEJ.