Response of Osteoarthritis Biomarkers After a Rehabilitation Program
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 4
- 主要终点
- Change from baseline to month 2 in Western Ontario and McMasters Universities Osteoarthritis (WOMAC) Index score
研究概览
简要总结
Osteoarthritis (OA) is the most common type of degenerative joint disease. Furthermore, despite its incidence being amongst the highest in chronic diseases, effective biomarkers, diagnostic aids and imaging technology are not available to assist in the management of OA. Mounting evidence suggests that non-pharmacological treatment such as exercise/physical therapy may lower the risk for onset or progression of OA by mitigating inflammation. However, the mechanical unloading and overloading, as seen in disuse and overuse, lead to upregulation of several proinflammatory molecules and enhance tissue degradation, whereas, dynamic moderate mechanical loading exerts anti-inflammatory and anti-catabolic effects on articular cartilage by suppressing mediators of inflammation. However, the lack of robust biomarkers to measure the effectiveness of physical therapies, represent a critical gap in biotechnology, obliterating the progress in the optimal application of these therapies. Our central hypothesis is that the circulating levels of specific molecules could serve as robust biomarkers for quantitative measures of OA burden, prognosis, progression or treatment efficacy. The objective of this project is to identify and evaluate mediators that serve as biomarkers of OA progression and treatment. Recently, high mobility group box chromosomal protein 1 (HMGB-1) has been suggested to be markedly upregulated in OA. However, presently there are no inhibitors of HMGB1 that could be used therapeutically. Previous results showed that that gentle exercise is the only tool that can mitigate HMGB1 production by local and systemic macrophages, and thus inflammation. Serum concentration of HMGB1 will be evaluate as a biomarker in OA patients and relate it to the functional capacity of knee joints in OA patients after rehabilitation protocol (RP). The RP will consist of three rehabilitation session/week during eight weeks. The efficacy of a RP will be evaluated by functional scale Western Ontario & McMaster Universities Osteoarthritis (WOMAC), Scale for the measurement of health related quality of life using EuroQol five dimensions questionnaire (EuroQOL), Visual Analog Scale (VAS), and physical function tests. Besides all clinical assessment, serum levels of classical pro-inflammatory cytokines, hyaluronan and HMGB1 will be evaluated. A correlation of physical improvement after RP and serum biomarkers will be performed.
详细描述
Detailed Description:
Methods/Design
- Participants after being textually and verbally informed about their rights, benefits and possible risks, objectives and methodologies of this study, all participants will sign a free and informed consent form.
- Study Design Prior to the rehabilitation protocol (RP), participants will perform one adaptation session to all the functional tests that will be applied to minimize learning bias. In the second session after 5 minutes warm up in a cycle ergometer (CEE), the Time Up and Go (TUG) test will be applied, followed by the isometric strength test. In the third day, after the same warm up, one repetition maximum testing will be conducted. At the end of the RP, all the tests will be repeated. Blood samples will be collected at baseline (day 0), 1 month (day 30 after RP) and at 2 months (day 60 after RP).
2.1. Rehabilitation protocol (RP) The RP will consist of 3 exercise session/week for 8 weeks. Each session will begin with the evaluation of pain by the participants. If the pain is higher than four, an analgesic protocol (AP) containing ultra-sound, laser or transcutaneous electrical nerve stimulation (TENS) will be applied. After the AP, the participant will just execute the rehabilitation protocol if the pain decreased to or lower than four. Starting with a warm up exercise in a cycle ergometer (CEE), for 5 minutes at free cadence, then the intensity will be set at 90% of the intensity obtained during the incremental test (see item 2.2a) and maintained for 10 min. Afterward, four sets (8-12 repetitions) of three different resistance exercises (RE) (leg press, knee extension and knee flexion) will be performed at 70% of the load correspondent to 1RM test (see item 2.2b) with one minute interval between sets and exercises. During CEE Borg scale will be taken every two minutes and during RE the omnibus (OMNI) scale taken at the end of every set to monitor the intensity. At the end of the session, cool down global stretching exercises for inferior members will be performed and the VAS evaluated again. Ten seconds of tension for each stretching position targeting the hamstrings, quadriceps, gluteus maxim ums, gastrocnemius, thigh adductors and abductors.
2.2. Rehabilitation intensity parameters.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 45 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Women and men aged 45-65 years
- •Clinical knee osteoarthritis according to the American College of Rheumatology Clinical Criteria
- •Kellgren and Lawrence (KL) radiographic osteoarthritis grade 2 and 3 (mild to moderate radiographic osteoarthritis)
排除标准
- •Severe knee osteoarthritis according to the KL classification (grade 4)
- •Other known major musculoskeletal impairments in the lower extremities or the back or prostheses in any joint of the lower extremities
- •Known serious coronary heart diseases or cancer
- •Body mass index >35
- •Scheduled for surgery in any joint
- •Persons who already perform sports related moderate physical activity more than two times a week
- •History of knee replacement surgery or high tibial osteotomy;
- •Any knee surgery or corticosteroid injections within the previous 6 months;
- •Miss more than two rehabilitation sessions during the program or more than two consecutive sessions.
结局指标
主要结局
Change from baseline to month 2 in Western Ontario and McMasters Universities Osteoarthritis (WOMAC) Index score
时间窗: Baseline and 2 month
Participants will answer the questionnaire WOMAC for the assessment of lower extremity pain, stiffness and physical function during daily activities. The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). For each item, the possible range of scores is therefore 0-100. Items are summed for each subscale, resulting in possible ranges as follows: pain=0-500, stiffness=0-200, physical function=0-1700. Most commonly, a total WOMAC score is created by summing the items for all three subscales. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. The collected data will be present through study completion, an average of 1 year.
次要结局
- Change from baseline to month 2 in TUG test(Baseline and 2 month)
- Change from baseline to month 2 in Health-related quality of life (EuroQOL-5D, EQ-5D)(Baseline and 2 month)
- Change from baseline in proinflammatory cytokines and biomarkers of cartilage breakdown in blood(Baseline, 1 month and 2 month after RP)
- Change from baseline to month 2 in Radiographic knee osteoarthritis progression (joint space and KL score)(Baseline and 2 month)
- Change from baseline to month 2 in VAS analysis.(Baseline and 2 month)
- Change from baseline to month 2 in Isometric strength testing(Baseline and 2 month)