Biologically Regulated Marrow Stimulation by Blocking Fibrosis to Improve Cartilage Repair: A Randomized Double-Blind, Placebo-Controlled Study
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-Emergent Adverse Events
研究概览
简要总结
Phase I/IIA randomized, double-blind, placebo-controlled clinical trial to assess safety and efficacy of oral losartan for improving cartilage repair following microfracture to treat focal cartilage defects during hip arthroscopy.
详细描述
This is a prospective, double-blind, placebo-controlled, randomized clinical trial that will be conducted at The Steadman Clinic and Steadman Philippon Research Institute.
Articular cartilage defects that extend full thickness to subchondral bone rarely heal without intervention. Some patients may not develop clinically significant problems from acute full-thickness chondral defects, but many eventually suffer from debilitating degenerative changes. Microfracture is the most commonly used first-line treatment technique for chondral lesions in the hip, however, this procedure's effectiveness is limited by the repair tissue being a hybrid of hyaline and fibrocartilage. We hypothesize that administration of a transforming growth factor beta 1 (TGF-β1) blocker, losartan (an approved hypertension drug, angiotensin II receptor antagonist) with microfracture will enhance articular cartilage repair as assessed on quantitative magnetic resonance imaging. We will also measure patient benefit through the recording of patient reported outcomes in the 18 months following surgery. The Division of Pulmonary, Allergy and Rheumatology Products within the Center for Drug Evaluation and Research at the Food and Drug Administration has granted an investigational new drug (IND) exemption to pursue this trial in accordance with 21 CFR 312.2(b).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Underwent primary hip arthroscopy
- •Underwent baseline quantitative MRI at The Steadman Clinic (TSC)
- •Single, localized, grade 3 or 4 cartilage lesion of the acetabulum or femoral head treated with Bone Marrow Stimulation (BMS; i.e. microfracture)
- •Aged 18-60 at time of surgery
- •Tonnis grade 1 or less
排除标准
- •Two or more cartilage lesions of grade 3 or 4
- •Less than 2 mm of minimal hip joint space
- •Osteoarthritis or diffuse change of cartilage
- •Non-English speaking
- •Prior hip surgery on operative hip
- •Pre-existing bony deformity caused by previous fracture(s)
- •Synovial chondromatosis
- •Pigmented Villonodular Synovitis (PVNS)
- •Dysplasia (center edge angle <20 degrees)
- •History of Avascular Necrosis (AVN), Perthes disease, or slipped capital femoral epiphysis (SCFE)
- •Inflammatory arthritis or other arthritis caused by autoimmune disease
- •Patients allergic to any active or inactive ingredient of losartan
- •Patients taking medication with known losartan interaction, including phenobarbital, rifampin, and fluconazole.
- •Subjects that are currently taking losartan
研究组 & 干预措施
Losartan
12.5mg Losartan capsules, oral administration, twice daily (25mg total per day), taken for 30 consecutive days starting on the evening of the second post-surgery day.
干预措施: Losartan (Drug)
Placebo
Appearance-matched placebo capsules, oral administration, twice daily, taken for 30 consecutive days starting on the evening of the second post-surgery day.
干预措施: Placebo (Other)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events
时间窗: Drug related adverse events will be monitored during the medication phase (post-op days 2-31) and orthopaedic-related health and function will be monitored for the entire study duration (18 months).
Occurrence of treatment-emergent adverse events
次要结局
- Patient Reported Outcomes Questionnaire - Patient Satisfaction(Baseline, 3 months, 6 months, 12 months and 18 months)
- Physical Examination of the Hip - Range of Motion(Baseline, 3 months, and 12 months)
- Patient Reported Outcomes Questionnaire - Western Ontario and McMaster Universities Osteoarthritis Index(Baseline, 3 months, 6 months, 12 months and 18 months)
- Patient Reported Outcomes Questionnaire - Tegner Activity Scale(Baseline, 3 months, 6 months, 12 months and 18 months)
- Patient Reported Outcomes Questionnaire - Numeric Rating Scale for Pain(Baseline, 3 months, 6 months, 12 months and 18 months)
- Patient Reported Outcomes Questionnaire(Baseline, 3 months, 6 months, 12 months and 18 months)
- Patient Reported Outcomes Questionnaire - Hip Outcome Score(Baseline, 3 months, 6 months, 12 months and 18 months)
- Physical Examination of the Hip - Strength(Baseline, 3 months, and 12 months)
- Morphological and Quantitative Magnetic Resonance Imaging (MRI)(Baseline and 12 months)
- Patient Reported Outcomes Questionnaire - Harris Hip Score(Baseline, 3 months, 6 months, 12 months and 18 months)