Acupuncture for Aromatase Inhibitor-Related Arthralgias in Breast Cancer Patients

描述(申请人提供)：第三代芳香酶抑制剂已被证明在提高早期激素受体阳性乳腺癌妇女的无病存活率、降低远处和局部复发率以及降低对侧乳腺癌发病率方面优于他莫昔芬。然而，接受人工智能治疗的女性中，高达50%的人报告了衰弱的肌肉骨骼疼痛和关节疼痛的症状，这可能会导致不遵从性和早期停止，从而影响生存。我们先前的II期随机研究(n=40)显示，与假针刺相比，针刺每周两次，连续6周，可以改善AI诱导的关节疼痛/僵硬，用修改的简短疼痛指数简表(mBPI-SF)衡量，疼痛评分恶化50%。拟议的第三阶段随机、假对照、盲目、多中心临床试验将考察针灸对200名I-III期乳腺癌女性患者自开始人工智能以来开始或增加的关节疼痛/僵硬的影响。女性将从四个机构招募，随机接受真针灸或假针灸，每周两次，持续6周，然后维持每周针灸或假针灸，持续6周。真正的针灸课程将包括标准化的全身和关节特定穴位处方和NADA耳穴方案。假针灸治疗将包括全身表面针刺和关节特定穴位处方，这些处方与任何真正的针灸穴位都不对应。基本的假设是，与假针灸相比，针刺6周后每周两次，然后每周6周，通过mBPI-SF评分衡量，将减轻AI引起的关节痛的女性的关节疼痛/僵硬。次级终点将评估从第6周到第12周的每周维持真针灸是否会保持第6周时的效果，以12周的mBPI-SF评分衡量，以及与假针灸相比，真正的针灸是否会有持久的效果，如24周的mBPI-SF评分。其他次要终点(将在基线、6周、12周和24周进行评估)包括1)通过自我管理的问卷(安大略省西部大学和麦克马斯特大学骨关节炎(WOMAC))对关节疼痛/僵硬和功能状态的额外评估，修改的手部慢性类风湿性关节炎影响评估和量化评分(M-SACRAH)和风湿学临床试验和骨关节炎研究学会国际标准(OMERACT-OARSI)中的结果测量，2)通过自填问卷进行的生活质量评估癌症治疗-乳房/内分泌分量表(FACT-B/ES)，3)止痛药的使用，4)功能测试(握力和“下肢定时起身”)和5)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，观察针灸对乳腺癌女性人工智能引起的关节痛的影响。 公共卫生相关性：芳香酶抑制剂已被证明可以延长被诊断为乳腺癌的妇女的生存时间。然而，由于关节疼痛等不良副作用，许多女性停止了这种延长生命的治疗。这项研究测试将证实针灸减轻芳香酶抑制剂引起的关节疼痛的先导随机试验的结果。我们建议对200名乳腺癌幸存者进行一项多中心随机、假对照研究。

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.