中藥方劑治療高尿酸血症之隨機分派雙盲安慰組控制臨床試驗

一、前言　　台灣的社會結構及、生活型態與飲食習性改變，致高尿酸血症與痛風的盛行率愈來愈高，民眾除了尋求西醫治療外，也希望中醫藥上有相對有效及副作用少的療法在慢性病治療所有突破。二、研究目的本研究擬使用中藥方劑──五苓散及茵陳五苓散──來治療高尿酸血症患者，並評估其療效及安全性。三、研究方法本研究方法採隨機分派雙盲試驗方式進行，符合收案條件患者，取得受試者同意書後，隨機分派成三組：五苓散、茵陳五苓散、安慰劑，受試者需服用試驗藥物4週，另後續追蹤4週。主要療效指標為第4週之血中尿酸值；次要療效指標含血糖、血中總膽固醇值、低密度脂蛋白、高密度脂蛋白、三酸甘油值、丙胺基轉移酶(SGPT)、肌酐酸(creatinine)、24小時尿中尿酸排泄量、血壓、體重、血中尿酸值<6 mg/dl之比例、痛風發作次數及副作用評估。四、研究結果本研究收案60名患者，並進行隨機、雙盲、安慰劑控制研究。初步顯示，「五苓散」、「茵陳五苓散」及安慰劑三組中於第4週的血中尿酸值< 6.0 mg/dl的比例無顯著性差異，三組血中尿酸值和尿中尿酸值於第4週皆無顯著性的減少，病患於服藥後第8週「茵陳五苓散」組之血中尿酸值比其他組別要低，達到統計顯著意義(p=0.034)。而「五苓散」及「茵陳五苓散」在第8週的尿酸下降幅度來得比安慰組要低(p<0.05)。與安慰劑比較，兩實驗組在體重、無壓、肝功能、三酸甘油酯、膽固醇、血糖、痛風發作次數及副作用上均無顯著差異。五、結論與建議　　雖然本研究的傳統中藥方劑在治療高尿酸血症及痛風上，未能達到原本研究設計的主要治療目標及次要治療目標，可是在第8週血中尿值在「茵陳五苓散」組是比「五苓散」組及安慰劑安慰低，而且兩種傳統方劑均無重大副作用。因此這兩方劑短期用於高尿酸血症之病患應是安全的。本研究需要更多樣本數及更長時間的研究來進一步驗證這兩首傳統中藥方劑在痛風及高尿酸症的療效及安全性。

Introduction: The prevalence of hyperuricemia and gout is increasing in Taiwan. It is probably contributed by adapting to Western diet and lifestyle. Previous studies have demonstrated the relationship between hyperuricemia with hypertension, metabolic syndrome, cardiovascular disease and chronic renal disease. While Western medicine shows promising effects in treating hyperuricemia and gout, we are searching for an alternative in traditional Chinese medicine with both safety and efficacy in treating hyperuricemia.Objective: To testify the efficacy and safety of traditional Chinese formulae, “Wu-Ling San” and “Yin-Chen Wu-Ling San” for patients with hyperuricemia.Methods:We conducted a randomized double-blinded placebo-controlled clinical trial in adults with hyperuricemia. Sixty patients with serum uric acid level more than 8 mg/dl were enrolled. Patients were then randomized into three arms: Traditional Chinese Medicine formulae: “Wu-Ling San”, “Yin-Chen Wu-Ling San” or placebo for 4 weeks. Efficacy and safety were evaluated at Week 2, 4 and 8. Primary endpoint was the serum uric acid<6 mg/dL at Week 4. Secondary endpoints were the differences between groups in serum uric acid at Week 2 and 8, serum SGPT, SGOT, creatinine, total cholesterol, triglycerides, HDL, LDL, fasting blood glucose, body weight, blood pressures and frequency of gouty attack at Week 4.Results: There were no significant differences among three arms on serum uric acid levels <6mg/dL at Week 4. The primary endpoint could not be reached in both “Wu-Ling” San and “Ying-Chen Wu-Ling San” groups. The uric acid level was lower in the “Yin-Chen Wi-Ling” arm at Week 8 (8.1 mg/dL vs 9.1 mg/dL, p=0.034). The changes in uric acid from baseline were significant in both “Wu-Ling San” and “Yin-Chen Wu-Ling San” arms (p<0.05). There were also no significant differences in the total cholesterol, triglyceride, liver function profiles, creatinine, blood pressures, body weight and amount of daily uric acid excretion. Conclusions: The two formulae in traditional Chinese medicine were relatively safe in treating the patients with hyperuricemia in short-term. There were no significant statistical difference in reaching the target—serum uric acid level <6mg/dL. However, we found that the changes in uric acid from baseline were more significant at Week 8 in both “Wu-Ling San” and “Ying-Chen Wu-Ling San”. Further studies with larger sample size and longer duration should be considered to confirm the safety and efficacy of the two tradition Chinese formulae.