Knee Osteoarthritis Outcome Measures in Arthritic Patients With Osteoporosis
2019年10月22日 更新者:Edward Fox
Pilot Study to Evaluate Knee Osteoarthritis Outcome Measures in Arthritic Patients Prescribed Forteo or Prolia for Osteoporosis
The purpose of this study is to generate proof of concept human data by evaluating osteoarthritis outcome measures in arthritic patients that are prescribed Forteo® as the standard of care to treat their primary diagnosis of osteoporosis.
研究概览
详细说明
The traditional treatment paradigm for osteoarthritis (OA) involves palliative strategies focused on pain management and joint replacement.
The longstanding inability to develop disease-modifying therapies that can rejuvenate joint cartilage is a great unmet need considering that diarthrodial and spinal OA is the most prevalent disease in the US, equal in numbers to the next top 4 disorders combined (heart, pulmonary, mental health and diabetic conditions) (CDC, 2009).
Thus, the development of an effective remittive treatment for OA is a vital public health initiative with potential for tremendous impact.
Our long-term research objective is to test a radically different strategy for treatment of OA that is based on findings recently published in Science Translational Medicine (Sampson et al., 2011) that identified human parathyroid hormone1-34 (teriparatide) as a chondroregenerative agent in a murine model of OA.
Suggesting a parallel effect in human OA, data mined from the NIH-sponsored OA Initiative revealed improved WOMAC knee function scores in arthritic subjects coincidentally prescribed teriparatide (trade name: Forteo®) to treat osteoporosis.
These preclinical and human data provide compelling rationale to study Forteo® as a novel OA therapy directed at improving joint structure and function.
The central aim of our overall research program is to challenge the paradigm that cartilage loss in OA is irreversible.
Thus, our long-term programmatic goal is to test Forteo® as the first and only disease-modifying treatment for OA with potential to rapidly impact clinical care.
To achieve this, we have been developing a clinical trial where subjects with medial compartment Kellgren Lawrence (K-L) stage II-III knee OA will receive either Forteo® or Prolia® (a brand of denosumab) for two years.
Disease progression will be assessed via structural, biomarker and functional outcomes at various time points out to 24 months post-initiation of therapy.
Since Forteo® is a widely used therapeutic in patients with osteoporosis (OP)-related severe bone loss, we propose to examine OA outcomes in OP patients with concomitant knee OA.
This pilot study described here that tests the hypothesis that patients with unilateral or bilateral knee OA (Kellgren-Lawrence grade II-III) that are prescribed Forteo® to treat their primary diagnosis of OP will demonstrate improved physical function (Timed-Up-And-Go), improved patient-reported outcomes (PROMIS 12a, v1.0), and increased blood levels in the cartilage anabolic marker type II collagen C-propeptide.
Completion of this proposed experimental design would provide critical proof-of-concept preliminary data supporting the use of biomarkers, physical function testing and questionnaire-based functional assessment to study OA in patients.
研究类型
观察性的
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
学习地点
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Pennsylvania
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Hershey、Pennsylvania、美国、17033
- Penn State Milton S. Hershey Medical Center
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参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
40年 至 80年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
取样方法
非概率样本
研究人群
patients that are evaluated, treated, and followed by the study investigator
描述
INCLUSION CRITERIA:
- Age: 40-80 years (inclusive)
- Gender: male or female (non-pregnant)
- Fluent in written and spoken English
- Patients capable of giving informed consent
- Primary diagnosis of osteoporosis that will be treated with either Forteo® to induce bone anabolism or Prolia® by the study investigator as part of patient's standard of care treatment
- Symptomatic, medial compartment knee OA with a Kellgren-Lawrence (K-L) score between II-III (documented in the medical record by previously collected knee series radiography). Radiographs to be performed within past two years.
EXCLUSION CRITERIA:
- Age < 40 or >80 years
- Cognitive impairment
- Pregnancy
- Non-English speaking persons
- History of hyperparathyroidism, hypercalcemia, current/recent renal stones, or malignancy
- Depression (currently taking home medication)
- History of inflammatory disease (colitis, rheumatoid arthritis, psoriasis, lupus, scleroderma, spondylitis)
- Use of immunosuppressants, chemotherapy, or radiotherapy
- BMI, angular deformity and K-L score of the contralateral knee (if the OA is bilateral) will be noted as covariates
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
研究是如何设计的?
设计细节
队列和干预
团体/队列 |
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Forteo
teriparatide 20-microgram once daily available in a 2.4-mL delivery device for subcutaneous injection by the patient
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Prolia
denosumab 60 mg administered as a single subcutaneous injection every 6 months by the health care provider
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Blood levels
大体时间:2 years
|
Type II collagen degradation neoepitope and C-propeptide
|
2 years
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Urine levels
大体时间:2 years
|
Type II collagen C-telopeptide
|
2 years
|
Physical function
大体时间:2 years
|
Timed-Up-And-Go
|
2 years
|
Patient reported outcomes
大体时间:2 years
|
PROMIS SF v1.0-Physical Function 12a
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2 years
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
赞助
调查人员
- 首席研究员:Edward J Fox, M.D.、Milton S. Hershey Medical Center
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Kraus VB, Feng S, Wang S, White S, Ainslie M, Brett A, Holmes A, Charles HC. Trabecular morphometry by fractal signature analysis is a novel marker of osteoarthritis progression. Arthritis Rheum. 2009 Dec;60(12):3711-22. doi: 10.1002/art.25012.
- Centers for Disease Control and Prevention (CDC). Prevalence and most common causes of disability among adults--United States, 2005. MMWR Morb Mortal Wkly Rep. 2009 May 1;58(16):421-6.
- Brostrom EW, Esbjornsson AC, von Heideken J, Iversen MD. Gait deviations in individuals with inflammatory joint diseases and osteoarthritis and the usage of three-dimensional gait analysis. Best Pract Res Clin Rheumatol. 2012 Jun;26(3):409-22. doi: 10.1016/j.berh.2012.05.007.
- Garnero P, Thompson E, Woodworth T, Smolen JS. Rapid and sustained improvement in bone and cartilage turnover markers with the anti-interleukin-6 receptor inhibitor tocilizumab plus methotrexate in rheumatoid arthritis patients with an inadequate response to methotrexate: results from a substudy of the multicenter double-blind, placebo-controlled trial of tocilizumab in inadequate responders to methotrexate alone. Arthritis Rheum. 2010 Jan;62(1):33-43. doi: 10.1002/art.25053.
- Aletaha D. From the item to the outcome: the promising prospects of PROMIS. Arthritis Res Ther. 2010;12(1):104. doi: 10.1186/ar2910. Epub 2010 Feb 1.
- Bischoff-Ferrari HA, Vondechend M, Bellamy N, Theiler R. Validation and patient acceptance of a computer touch screen version of the WOMAC 3.1 osteoarthritis index. Ann Rheum Dis. 2005 Jan;64(1):80-4. doi: 10.1136/ard.2003.019307. Epub 2004 Jul 1.
- Fries JF, Krishnan E, Rose M, Lingala B, Bruce B. Improved responsiveness and reduced sample size requirements of PROMIS physical function scales with item response theory. Arthritis Res Ther. 2011;13(5):R147. doi: 10.1186/ar3461. Epub 2011 Sep 14.
- Sampson ER, Hilton MJ, Tian Y, Chen D, Schwarz EM, Mooney RA, Bukata SV, O'Keefe RJ, Awad H, Puzas JE, Rosier RN, Zuscik MJ. Teriparatide as a chondroregenerative therapy for injury-induced osteoarthritis. Sci Transl Med. 2011 Sep 21;3(101):101ra93. doi: 10.1126/scitranslmed.3002214.
- Hashimoto J, Garnero P, van der Heijde D, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Yoshikawa H, Nishimoto N. A combination of biochemical markers of cartilage and bone turnover, radiographic damage and body mass index to predict the progression of joint destruction in patients with rheumatoid arthritis treated with disease-modifying anti-rheumatic drugs. Mod Rheumatol. 2009;19(3):273-82. doi: 10.1007/s10165-009-0170-4. Epub 2009 May 19.
- Maksymowych WP, Poole AR, Hiebert L, Webb A, Ionescu M, Lobanok T, King L, Davis JC Jr. Etanercept exerts beneficial effects on articular cartilage biomarkers of degradation and turnover in patients with ankylosing spondylitis. J Rheumatol. 2005 Oct;32(10):1911-7.
- Papuga MO, Beck CA, Kates SL, Schwarz EM, Maloney MD. Validation of GAITRite and PROMIS as high-throughput physical function outcome measures following ACL reconstruction. J Orthop Res. 2014 Jun;32(6):793-801. doi: 10.1002/jor.22591. Epub 2014 Feb 14.
- Taylor ME, Delbaere K, Mikolaizak AS, Lord SR, Close JC. Gait parameter risk factors for falls under simple and dual task conditions in cognitively impaired older people. Gait Posture. 2013 Jan;37(1):126-30. doi: 10.1016/j.gaitpost.2012.06.024. Epub 2012 Jul 23.
- Debi R, Mor A, Segal G, Segal O, Agar G, Debbi E, Halperin N, Haim A, Elbaz A. Correlation between single limb support phase and self-evaluation questionnaires in knee osteoarthritis populations. Disabil Rehabil. 2011;33(13-14):1103-9. doi: 10.3109/09638288.2010.520805. Epub 2011 Jan 5.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (预期的)
2020年1月1日
初级完成 (预期的)
2023年12月31日
研究完成 (预期的)
2024年12月31日
研究注册日期
首次提交
2017年7月12日
首先提交符合 QC 标准的
2017年7月12日
首次发布 (实际的)
2017年7月14日
研究记录更新
最后更新发布 (实际的)
2019年10月24日
上次提交的符合 QC 标准的更新
2019年10月22日
最后验证
2019年10月1日
更多信息
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