Altering Bone Microarchitecture and Mechanics by Off-label Pharmaceutical Intervention
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Bone microarchitecture changes at 6 months as assessed by high resolution peripheral quantitative computed tomography (HR-pQCT)
研究概览
简要总结
The purpose of this study is to assess if a zoledronic acid injection can alter the trajectory of joint degeneration following an acute anterior cruciate ligament (ACL) injury.
详细描述
After being informed about the study and potential risks and all participants giving written informed consent, this project will establish a cohort of young men and women who within six weeks have sustained an acute rupture of the ACL. The cohort is randomized into a control and treatment group, where the treatment group receives a zoledronic acid injection at baseline. The cohort will be followed radiographically with high resolution peripheral quantitative computed tomography (HR-pQCT), dual-energy computed tomography (DECT), digital radiography (X-Ray), bi-planar X-ray (EOS) and magnetic resonance imaging (MRI) for eighteen months to monitor the progression of joint changes and the effects of zoledronic acid.
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
- Single (Participant)
入排标准
- 年龄范围
- 25 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical evidence of an acute unilateral ACL tear (full-thickness, complete tear) will be recruited. This age range is chosen to ensure participants have fully developed adult bone structures and to exclude participants with menopause as this could affect study results.
- •Participants with combined ligament deficiencies (posterior cruciate, medial and/or lateral collateral) or meniscal injury will be included. Participants must be able to fully extend the knee while supported at the time of the baseline measurement in order to conduct the HR-pQCT scan.
- •Participants with a serum calcium level in the normal range (2.10-2.60 mmol/L) and a creatinine level above 59 (reported as eGFR) will be included.
排除标准
- •Individuals with contraindications to zoledronic acid (see below)
- •Prior knee ligament and/or meniscus tears, and/or intra-articular fractures.
- •Females who are pregnant or planning pregnancy within a year will not be eligible. The research team will recommend participants who are planning to become pregnant within the next five years to withdraw their participation.
- •Individuals with knees larger than the CT scanner's circular field of view.
- •Individuals with a history of disease and/or treatment affecting bone turnover in the past 12 months.
- •Individuals with injuries or implants that are not MRI-safe.
- •Zoledronic acid is contraindicated for:
- •Patients who are hypersensitive to this drug or to any ingredient in the formulation, or to any bisphosphonates or component of the container.
- •Severe renal impairment with creatinine clearance <35 mL/min and in those with evidence of acute renal impairment. For this study, participants with a creatinine clearance <50 mL/min may be excluded.
- •Non-corrected hypocalcaemia at the time of infusion.
- •Pregnant and nursing mothers.
- •Patients who are already taking another bisphosphonate (ex. for osteoporosis).
研究组 & 干预措施
Zoledronic Acid Injection
Participants will receive 1 dose of 5 mg/100 mL intravenous zoledronic acid
干预措施: Zoledronic Acid Injection (Drug)
Placebo
Participants will receive 1 dose 100 ml Saline.
干预措施: Placebo (Drug)
结局指标
主要结局
Bone microarchitecture changes at 6 months as assessed by high resolution peripheral quantitative computed tomography (HR-pQCT)
时间窗: Baseline, 6 months
To determine morphological parameters from HR-pQCT scans, the trabecular portion must be isolated from the cortical shell of the bone in order to analyse the components separately. This is accomplished with an already developed auto-segmentation algorithm. In addition, the raw HR-pQCT images must be converted to binary images, wherein each voxel (3D pixel) is either labelled 'bone' or 'not bone.' This segmentation is performed by an algorithm which applies either a Gaussian or Laplace-Hamming filter in addition to a threshold to the grey-scale images. The binary images can then be analysed and morphological parameters can be determined. The changes in bone microarchitecture will be assessed at 6 months in comparison to baseline.
Bone microarchitecture changes at 18 months as assessed by high resolution peripheral quantitative computed tomography (HR-pQCT)
时间窗: Baseline, 18 months
To determine morphological parameters from HR-pQCT scans, the trabecular portion must be isolated from the cortical shell of the bone in order to analyse the components separately. This is accomplished with an already developed auto-segmentation algorithm. In addition, the raw HR-pQCT images must be converted to binary images, wherein each voxel (3D pixel) is either labelled 'bone' or 'not bone.' This segmentation is performed by an algorithm which applies either a Gaussian or Laplace-Hamming filter in addition to a threshold to the grey-scale images. The binary images can then be analysed and morphological parameters can be determined. The changes in bone microarchitecture will be assessed at 18 months in comparison to baseline.
次要结局
- Bone marrow lesions (BML) and soft tissue injury changes at 2 months as assessed by Magnetic Resonance Imaging (MRI)(Baseline, 2 months)
- Bone marrow lesions (BML) and soft tissue injury changes at 18 months as assessed by MRI(Baseline, 18 months)
- Bone marrow lesions (BML) and soft tissue injury changes at 6 months as assessed by MRI(Baseline, 6 months)
- Knee alignment as assessed by bi-planar x-ray(Baseline)
- Patient reported outcomes using ACL Quality of Life Questionnaire - Baseline(Baseline)
- Patient reported outcomes using ACL Quality of Life Questionnaire - 2 Months(2 Months)
- Patient reported outcomes using ACL Quality of Life Questionnaire - 6 Months(6 Months)
- Patient reported outcomes using ACL Quality of Life Questionnaire - 18 Months(18 Months)
- Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) - Questionnaire - Baseline(Baseline)
- Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire - 2 Months(2 months)
- Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire - 6 Months(6 months)
- Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire - 18 Months(18 months)
- Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - Baseline(Baseline)
- Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - 2 months(2 months)
- Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - 6 months(6 months)
- Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - 18 months(18 months)
- Patient reported outcomes using EQ-5D-5L Questionnaire - Baseline(Baseline)
- Patient reported outcomes using EQ-5D-5L Questionnaire - 2 months(2 months)
- Patient reported outcomes using EQ-5D-5L Questionnaire - 6 months(6 months)
- Patient reported outcomes using EQ-5D-5L Questionnaire - 18 months(18 months)
- Patient reported outcomes Health History Questionnaire (HHQ) - Baseline(Baseline)
- Patient reported outcomes Health History Questionnaire (HHQ) - 2 months(2 months)
- Patient reported outcomes Health History Questionnaire (HHQ) - 6 months(6 months)
- Patient reported outcomes Health History Questionnaire (HHQ) - 18 months(18 months)