Acupuncture for Aromatase Inhibitor-Related Arthralgias in Breast Cancer Patients

描述（由申请人提供）：第三代芳香酶抑制剂已被证明在改善早期激素受体阳性乳腺癌女性的无病生存期、降低远处和局部复发率以及降低对侧乳腺癌发生率方面优于他莫昔芬上级。然而，高达50%的AI女性报告了使人衰弱的肌肉骨骼疼痛和关节痛的症状，这可能导致不依从和早期停药，从而影响生存。我们先前的II期随机研究（n=40）显示，与假针灸相比，每周两次给予针灸持续6周改善AI诱导的关节疼痛/僵硬，如通过改良的简明疼痛指数简表（mBPI-sf）测量的，疼痛评分恶化50%。拟议的III期随机、假对照、盲法、多中心临床试验将研究针灸对200名患有I-III期乳腺癌的女性自AI开始以来开始或增加的关节疼痛/僵硬的影响。将从四个机构招募女性，并随机分配至每周两次的真针灸或假针灸，持续6周，然后维持每周针灸或假针灸6周。真正的针灸疗程将包括标准化的全身和关节特定穴位处方和NADA耳穴协议。假针灸治疗将包括全身和关节特定穴位处方的浅表针刺，这些穴位与任何真正的穴位都不对应。主要假设是，与假针灸相比，每周两次，持续6周，然后每周一次，持续6周，将减少AI诱导的关节痛女性的关节疼痛/僵硬，如在6周时通过mBPI-SF评分测量的。次要终点将评估从第6周至第12周的每周维持真针灸是否将维持第6周观察到的效果，如在第12周通过mBPI-SF评分测量的，以及与假针灸相比，真针灸是否将具有持久的效果，如在第24周通过mBPI-SF评分测量的。其他次要终点（在基线、第6、12和24周进行评价）包括1）通过自我问卷对关节疼痛/僵硬和功能状态进行额外评估（西安大略和麦克马斯特大学骨关节炎（WOMAC），手部慢性风湿病的改良评分（M-SACRAH）和流变学临床试验和骨关节炎研究协会国际标准的结局指标（OMERACT-OARSI），2）通过自填式问卷进行生活质量评估癌症治疗功能评估-乳腺/内分泌子量表（FACT-B/ES），3）镇痛剂使用，4）功能测试（握力和下肢“定时起床和行走”）和5）探索性激素和炎症生物标志物。这项研究将是第一个大型多中心干预试验，旨在观察针灸对乳腺癌女性AI诱导的关节痛的影响。 公共卫生相关性：芳香化酶抑制剂已被证明可以改善诊断为乳腺癌的妇女的生存时间。然而，许多女性由于不必要的副作用（如关节疼痛）而停止这种延长寿命的治疗。这项研究测试将证实针灸减少芳香化酶诱导的关节疼痛的初步随机试验的结果。我们提出了一个多中心的随机，假对照研究200乳腺癌幸存者。

DESCRIPTION (provided by applicant): Third generation aromatase inhibitors have been shown to be superior to tamoxifen in improving disease free survival, decreasing distant and local recurrence rates and decreasing incidence of contra-lateral breast cancer in women with early stage hormone receptor positive breast cancer. However, up to 50% of women on AI report symptoms of debilitating musculoskeletal pain and joint arthralgia that can lead to noncompliance and early discontinuation, thereby impacting survival. Our previous phase II randomized study (n=40) showed that acupuncture administered twice weekly for 6 weeks compare to sham acupuncture improve AI induced joint pain/stiffness as measured by modified Brief Pain Index short form (mBPI-sf) worse pain score by 50%. The proposed phase III randomized, sham controlled, blinded, multi-centered clinical trial will look at the effects of acupuncture on joint pain/stiffness that started or increased since initiation of AI in 200 women with Stage I-III breast cancer. Women will be recruited from four institutions and randomized to either true acupuncture or sham acupuncture administered twice weekly for 6 weeks follow by maintenance weekly acupuncture or sham acupuncture for 6 weeks. True acupuncture sessions will consists of standardized full body and joint specific point prescription and the NADA auricular protocol. The sham acupuncture treatment will consist of superficial needling at full body and joint specific point prescriptions that do not correspond to any true acupuncture points. The primary hypothesis is that acupuncture administered twice weekly for 6 weeks then weekly for 6 weeks will reduce joint pain/stiffness in women with AI induced arthragia as measured by mBPI-SF scores at 6 weeks compared to sham acupuncture. Secondary endpoints will assess whether weekly maintenance true acupuncture from week 6 to week 12 will maintain the effects seen at week 6 as measured by mBPI-SF score at 12 weeks and whether true acupuncture will have a durable effect as measure by mBPI-SF score at 24 weeks, compared to sham acupuncture. Other secondary endpoint (to be evaluated at baseline, 6, 12 and 24 weeks) include 1) additional assessment of joint pain/stiffness and functional status via self administered questionnaires (Western Ontario and McMaster Universities Osteoarthritis (WOMAC), Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH) and Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International criteria (OMERACT-OARSI), 2) quality of life assessment via the self administered questionnaire Functional Assessment of Cancer Therapy- Breast/Endocrine subscale (FACT-B/ES), 3) analgesic use, 4) functional testing (grip strength and "timed get up and go' for lower extremity") and 5) exploratory hormonal and inflammatory biomarkers. This study will be the first large multi-center center intervention trial looking at the effects of acupuncture on AI induced arthragia in women with breast cancer. PUBLIC HEALTH RELEVANCE: Aromatase inhibitors have been shown to improve the survival time of women diagnosed with breast cancer. However, many women discontinue this life extending therapy due to unwanted side effect such as joint pain. This study tests will confirm the findings of a pilot randomized trial of acupuncture for decreasing aromatase inhibitor-induced joint pain. We propose a multicenter randomized, sham-controlled study of 200 breast cancer survivors.