| Abstract: | 研究目的
骨關節炎（Osteoarthritis，OA）為最常見的軟骨退化疾病，目前對於OA治療以症狀減緩為主，大多使用口服非類固醇的消炎止痛藥，然而，這些用藥在臨床上已證實有明顯的副作用，特別是對胃腸、心血管及腎臟系統。過去研究顯示六味地黃丸 (Liu-Wei-Die-Huang-Wan，LWDHW) 可能有抑制發炎的趨勢，並且在臨床經驗上發現此方劑對於膝蓋退化性關節炎患者似乎有良好療效，因此本研究透過一個雙盲安慰劑對照的臨床試驗來確認六味地黃丸對OA的有效性及安全性評估。
研究方法
本研究採用單一中心、平行、隨機、雙盲、第二期、安慰劑對照式臨床試驗，納入研究樣本為81位確診膝蓋或髖關節退化之骨關節炎患者。經2：1隨機分派後，54位分派至治療組服用中藥複方，27位分派到安慰劑組，進行為期8週臨床試驗。主要療效指標為兩組於第8週之WOMAC （Western Ontario and McMaster Universities） osteoarthritis index相較於第0週之差異。其他次要療效指標包含疼痛視覺類比量表（Visual analogue scale for pain，VAS）、SF-36健康生活品質量表 （36-Item Short Form Health Survey，SF-36）、病人整體評估（patient global assessment，PGA）及抽血發炎指標高敏感性C-反應蛋白（High sensitivity C-Reactive Protein，Hs-CRP）、紅血球沉降率（Erythrocyte sedimentation rate，ESR）。
試驗結果
本研究共篩選83位受試者，其中有2位因無法配合而篩選失敗，其餘81位受試者均符合篩選條件並進一步地以隨機分派的方式到治療組 (n = 54) 與安慰劑組 (n = 27)。基線(baseline)觀察到的所有數值在治療組及安慰劑組間並未達統計顯著差異，第8週與第0週的差異比較可發現WOMAC的body pain在治療組有下降趨勢 (LWDHW -2.00 (3.00) vs Placebo -1.00 (4.00), P=0.471)，SF-36治療組有上升趨勢 (LWDHW 40.87 ± 80.70 vs Placebo 13.43 ± 101.90, P=0.193)，收縮壓(SBP)在治療組則有顯著下降 (LWDHW -15.00 (5.50) mmHg vs Placebo 0.00 (25.00) mmHg, P=0.022)，此外，將所有病人以BCQ體質量表區分比較治療組與安慰劑組的差異，可看到第8週與第0週SF-36 (LWDHW 48.61 ± 94.53 vs Placebo -36.18 ± 88.24, P=0.02)及body pain (LWDHW 9.52 ±19.58 vs Placebo -1.00 ± 9.42, P=0.04)在體質為陰虛型之患者治療組與安慰劑組有達統計顯著差異。
結論
本研究為隨機雙盲安慰劑對照式臨床試驗，發現六味地黃丸有改善骨關節炎患者症狀的趨勢，但主要結局指標與安慰劑相比並無統計差異。六味地黃丸對體質為陰虛型患者可顯著改善患者的身體疼痛，印證六味地黃丸為滋陰補腎的方劑。另外，本研究也發現六味地黃丸有輕微改善血壓的趨勢。副作用發生率在治療組與對照組無統計差異，顯示六味地黃丸具有良好的安全性。
Objective
Osteoarthritis (OA) is the most common arthritis. Nonsteroidal anti-inflammatory drugs (NSAIDS) are usually used for relieving pain and inflammation in OA patients. However, NSAIDs have potential serious adverse events including gastrointestinal bleeding, cardiovascular thrombotic events and renal function. Some studies indicated that Liu-Wei-Die-Huang-Wan (LWDHW) might have potential in anti-inflammation effect in knee OA in previous studies. Therefore, we conducted this eight-weeks double blind randomized placebo-controlled clinical trial to evaluate the efficacy and safety of Traditional Chinese Medicine Formula LWDHW in patient with knees or hips OA.
Methods
This study was an 8 weeks’ randomized, double-blind, placebo-controlled clinical trial. Eighty-one patients of osteoarthritis of knees or hips were enrolled in this study. Patients were 2:1 randomized to TCM treatment group (n=54) or placebo group (n=27). Primary endpoint was total score of Western Ontario and McMaster Universities (WOMAC) osteoarthritis index. Secondary outcome measures were pain visual analogue scale (VAS), Quality of life by 36-Item Short Form Health Survey (SF-36), patient global assessment (PGA), serum High sensitivity C-Reactive Protein (Hs-CRP) and Erythrocyte sedimentation rate (ESR).
Results
After 8 weeks’ treatment, in the intention-to-treat (ITT) population, there is mild reduction in WOMAC-body pain in the LWDHW group but not statistically significant compared with placebo group (LWDHW -2.00 (10.00) vs Placebo -5.00 (12.00), P=0.471). In the SF-36, there is mild improved in LWDHW group but not but not statistically significant compared with placebo group (LWDHW 40.87 ± 80.70 vs Placebo 13.43 ± 101.90, P=0.193). However, mild reduction of systolic blood pressure was noted in the LWDHW group and statistically significant compared with placebo group (LWDHW -15.00 (5.50) mmHg vs Placebo 0.00 (25.00) mmHg, P=0.022). In subgroup with deficiency of Yin by BCQ questionnaire, there is significant improved of SF-36 (LWDHW 48.61 ± 94.53 vs Placebo -36.18 ± 88.24, P=0.02) and sub question-body pain (LWDHW 9.52 ± 19.58 vs Placebo -1.00 ± 9.42, P=0.04) in LWDHW group compared to placebo group.
Conclusion
In this 8 weeks’ double blind, randomized clinical trial, the primary endpoint was not met. However, LWDHW group showed mild improvement of pain and quality of life in patients with knees or hips OA in subgroup with deficiency of Yin. Besides, mild reduction of systolic blood pressure was noted in the LWDHW group. There was no significant difference in other endpoints. LWDHW was well tolerated. |
