Identification of Novel Molecular Targets for the Development of Therapies in Patients With Rheumatoid Arthritis Responsive to Disease-modifying Antirheumatic (DMARDs) But Wirh Progressive Bone Erosion (AREOS)
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Protein analysis
研究概览
简要总结
Aims of this study is to identify the mechanisms of the dissociation between the inflammatory activity and the joints destruction in patients with rheumatoid arthritis (RA) in remission but presenting a progression of the bone erosions.
160 total patients will be enrolled. Males and females RA patients in clinical remission or not, osteoarthritis patients and patients hospitalized for any other orthopedics pathology (used as controls) will be enrolled. From RA patients with bone erosion, OA patients and controls whole blood will be collected; from RA patients without bone erosion whole blood will be collected. From whole blood mononuclear cells will be isolated and plasma will be harvested. From both RA and OA patients synovial fluid will be collected along with mononuclear cells present in this fluid and from both RA and OA patients candidate for total articular replacement fragments of synovial membrane, cartilage, bone and bone marrow will be collected during surgery as waste material.
The nuclear cells isolated from whole blood, synovial fluid and bone marrow will be characterized using a panel of markers. Protein arrays on plasma samples obtained from RA, OA patients and controls will be performed to identify a panel of acute phase proteins, cytokines and chemokines present at systemic levels and to highlight analogies and differences in the systemic protein profile.
The synovial fluid will be used to identify the proteins present in the synovial fluid of RA and OA patients. The main identified target will be quantified and used as markers of erosion progression, to develop intra-articular pharmacological therapies and to suggest the therapeutic doses of drugs. The same kind of analysis will be performed even on tissues obtained from surgical patients (RA and OA patients) to establish the pathways involved and the tissue specific targets to be stimulated, i.e. with trophic factors, to promote the tissue homeostasis after switching-off the autoimmune and inflammatory processes.
详细描述
The general aim is to study the mechanisms of the dissociation between the inflammatory activity and the joints destruction in patients with rheumatoid arthritis (RA) in remission but presenting a progression of the bone erosions.
The primary aim is to detect differences between patients with AR in clinical remission, but presenting progressive articular erosion and patients in complete clinical and radiological remission, by characterizing the proteins, particularly the chromogranin A (CHGA), present both at articular and systemic levels.
The secondary aims are: to characterize the cellular inflammatory intra-articular infiltrate and the cells of the immune system present in the circulation; to characterize protein profile of the cells resident in the synovium, cartilage and bone of the damaged articulation. It is hypothesized that with this approach it is possible to detect protein or cellular markers able to identify early the patients at risk to progress towards articular erosion and to identify specific cellular and protein targets for the development of local or systemic therapies suitable for the control of the erosive RA.
This is a, observational with additional procedure, court, prospective study. 160 patients 80 RA patients (Group 1) of which:
- Group 1A: at least 10 patients, maximum 70,with RA in remission, but presenting progressive bone erosion who must undergo a surgical procedure.
- Group 1B: at least10 patients maximum 70, with RA in remission, without bone erosion A group of 80 controls,
- Group 2: 10 patients with osteoarthritis (OA) who must undergo a surgical procedure.
- Group 3:70 without RA and OA but hospitalized for any other orthopedics pathology who must undergo a surgical procedure.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •- patients with:
- •rheumatoid arthritis treated with Disease-Modifying Antirheumatic Drugs (DMARDs), in remission but with progressive bone erosion who must undergo a surgical procedure (Group 1A).
- •rheumatoid arthritis treated with DMARDs, in remission without bone erosion (Group 1B)
- •osteoarthritis who must undergo a surgical procedure (Group 2).
- •any other orthopedics pathology who must undergo a surgical procedure (Group 3).
排除标准
- •age < 18 or > 75 years old
结局指标
主要结局
Protein analysis
时间窗: 2nd year
To detect differences between patients with AR in clinical remission, but presenting progressive articular erosion and patients in complete clinical and radiological remission, by characterizing: - the proteins, particularly the chromogranin A (CHGA), present both at articular and systemic levels.
次要结局
- Protein profile(3rd year)
- Inflammatory cell analysis(2nd year)