Multi-Center Pilot Study to Evaluate Concentrated Bone Marrow Aspirate (cBMA) as a Treatment to Modify Post-Traumatic Osteoarthritis (PTOA) Following Revision Anterior Cruciate Ligament Reconstruction (ACLR)
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Change from baseline in patient reported knee pain
研究概览
简要总结
The goal of this pilot randomized clinical trial is to look into the efficacy of concentrated bone marrow aspirate (cBMA) in improving post traumatic osteoarthritis (PTOA) symptoms in patients undergoing revision anterior cruciate ligament reconstruction surgery. The main questions it aims to answer are whether clinical outcomes, such as pain, are improved in patients who get cBMA with surgery, if there is a change in circulating markers of inflammation and what part of the cellular and molecular composition of cBMA may explain its effects.
详细描述
Anterior cruciate ligament reconstruction (ACLR) surgery is considered a relatively safe and effective procedure, however, up to 18% of grafts will fail and require revision surgery. Some studies have shown that these patients may be at increased risk of worse clinical outcomes, including fast progression toward post-traumatic osteoarthritis (PTOA). This is likely in part due to the inflammatory environment created within the joint. Concentrated bone marrow aspirate (cBMA) is a regenerative medicine therapy that contains soluble factors and connective tissue progenitor cells which may have immunomodulatory and pro-regenerative potential. The use of this therapy in conjunction with standard of care surgical treatment may help reduce the inflammatory microenvironment inside the joint, therefore modifying the conditions that might lead to developing long term complications such as PTOA.
The investigators hypothesize that cBMA treatment at the time of revision ACLR may improve clinical outcomes at 1 year after surgery and reduce the risk of developing PTOA-associated symptoms.
Participants will be randomized to either get a cBMA injection (investigational arm) at the time of surgery or a placebo incision (control arm). Biological specimens (blood, urine, synovial fluid), imaging data, functional tests and patient reported clinical outcomes will be measured at different time points during the study, for up to two years after the surgery. This will allow the investigators to evaluate the effect of cBMA in clinical outcomes. Biological specimens will be analyzed using molecular biology techniques to determine their composition, including the concentration of cells and other inflammatory markers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and Females
- •Age 18 to 55
- •Previous unilateral ACLR (Anterior Cruciate Ligament Reconstruction) within the last 5 years, and identified as having experienced failure of the primary ACLR
- •Scheduled to have a revision ACLR surgery, with any graft type (including patellar tendon, hamstring, quad or allograft)
- •Able to complete all study procedures and participate in a standardized physical therapy program
排除标准
- •History of inflammatory arthritis or joint sepsis
- •Prior or concurrent total or sub-total meniscectomy
- •Prior or present avascular necrosis of the index knee
- •Oral or intra-articular corticosteroid injection within 3 months
- •Hyaluronic acid or PRP (Platelet-Rich Plasma) injection within 6 months
- •Use of duloxetine, doxycycline, indomethacin, glucosamine and/or chondroitin (ongoing or within 2 months)
- •Any clinical or laboratory abnormality greater than grade 3 CTCAE, which in the view of the investigator, will compromise the participant's safety.
- •Planned arthroplasty in the index knee
研究组 & 干预措施
Investigational Arm
Patients undergoing revision anterior cruciate ligament reconstruction surgery will get an intraoperative injection of concentrated bone marrow aspirate (cBMA).
干预措施: Concentrated Bone Marrow Aspirate Injection (Biological)
Investigational Arm
Patients undergoing revision anterior cruciate ligament reconstruction surgery will get an intraoperative injection of concentrated bone marrow aspirate (cBMA).
干预措施: Revision Anterior Cruciate Ligament Reconstruction (Procedure)
Control Arm
Patients undergoing revision anterior cruciate ligament reconstruction surgery will get a sham incision in lieu of bone marrow harvesting.
干预措施: Sham Incision (Procedure)
Control Arm
Patients undergoing revision anterior cruciate ligament reconstruction surgery will get a sham incision in lieu of bone marrow harvesting.
干预措施: Revision Anterior Cruciate Ligament Reconstruction (Procedure)
结局指标
主要结局
Change from baseline in patient reported knee pain
时间窗: Baseline, 6 weeks, 6 months, 12 months and 24 months post-operative
The primary outcome measured for this study will be postoperative knee pain. This will be achieved using the Knee Injury and Osteoarthritis Outcome Score (KOOS) standardized questionnaire, which will be electronically delivered to participants at baseline and at 6-weeks, 6-months, 12-months and 24-months postoperatively. This questionnaire measures 42 items in a Likert scale for 5 different dimensions: pain, other symptoms, activities of daily living, function in sports and recreation and knee-related quality of life. The questionnaire is scored as a percentage from 0 to 100, with 0 representing extreme knee problems and 100 indicating no knee related symptoms, and therefore better outcomes.
次要结局
- Change from baseline in articular cartilage relative proteoglycan content and collagen fibril organization(Baseline, 12 months postoperative)
- Expression of local inflammatory biomarkers(Baseline and 6 weeks post-operative)
- Concentration of circulating inflammatory biomarkers(Baseline, 6 weeks and 12 months post-operative)
- Change from baseline in cartilage morphology(Baseline, 12 months post-operative)