Clinical trial NCT05204836: Altering Bone Microarchitecture and Mechanics by Off-label Pharmaceutical Intervention Following an Acute Knee Injury
Official title: Altering Bone Microarchitecture and Mechanics by Off-label Pharmaceutical Intervention
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Anterior Cruciate Ligament Tear
Anterior Cruciate Ligament Rupture
Anterior Cruciate Ligament Injuries
Osteo Arthritis Knee
Keywords: acl tear
acl
acl rupture
acl injury
osteo arthritis
Lead sponsor: University of Calgary
Sponsor class: OTHER
First posted: 2022-01-24
Enrollment: 56
Sex: ALL
Minimum age (years): 25
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The cohort is randomized into a control and treatment group, where the treatment group receives a zoledronic acid injection within 6 weeks of ACL injury.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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 (2.1-2.55 mmol/L) and a creatinine level above 50 (reported as eGFR) will be included.

Exclusion Criteria:

* 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).

Primary outcomes:
measure: Bone microarchitecture changes at 6 months as assessed by high resolution peripheral quantitative computed tomography (HR-pQCT)
timeFrame: Baseline, 6 months
measure: Bone microarchitecture changes at 18 months as assessed by high resolution peripheral quantitative computed tomography (HR-pQCT)
timeFrame: Baseline, 18 months
Secondary outcomes:
measure: Bone marrow lesions (BML) and soft tissue injury changes at 2 months as assessed by Magnetic Resonance Imaging (MRI)
timeFrame: Baseline, 2 months
measure: Bone marrow lesions (BML) and soft tissue injury changes at 6 months as assessed by MRI
timeFrame: Baseline, 6 months
measure: Knee alignment as assessed by bi-planar x-ray
timeFrame: Baseline
measure: Patient reported outcomes using ACL Quality of Life Questionnaire - Baseline
timeFrame: Baseline
measure: Patient reported outcomes using ACL Quality of Life Questionnaire - 2 Months
timeFrame: 2 Months
measure: Patient reported outcomes using ACL Quality of Life Questionnaire - 6 Months
timeFrame: 6 Months
measure: Patient reported outcomes using ACL Quality of Life Questionnaire - 18 Months
timeFrame: 18 Months
measure: Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) - Questionnaire - Baseline
timeFrame: Baseline
measure: Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire - 2 Months
timeFrame: 2 months
measure: Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire - 6 Months
timeFrame: 6 months
measure: Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire - 18 Months
timeFrame: 18 months
measure: Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - Baseline
timeFrame: Baseline
measure: Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - 2 months
timeFrame: 2 months
measure: Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - 6 months
timeFrame: 6 months
measure: Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - 18 months
timeFrame: 18 months
measure: Patient reported outcomes using EQ-5D-5L Questionnaire - Baseline
timeFrame: Baseline
measure: Patient reported outcomes using EQ-5D-5L Questionnaire - 2 months
timeFrame: 2 months
measure: Patient reported outcomes using EQ-5D-5L Questionnaire - 6 months
timeFrame: 6 months
measure: Patient reported outcomes using EQ-5D-5L Questionnaire - 18 months
timeFrame: 18 months
measure: Patient reported outcomes Health History Questionnaire (HHQ) - Baseline
timeFrame: Baseline
measure: Patient reported outcomes Health History Questionnaire (HHQ) - 2 months
timeFrame: 2 months
measure: Patient reported outcomes Health History Questionnaire (HHQ) - 6 months
timeFrame: 6 months
measure: Patient reported outcomes Health History Questionnaire (HHQ) - 18 months
timeFrame: 18 months
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
Study officials:
affiliation: University of Calgary
name: Steven Boyd, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Calgary
name: Gregory Kline, MD
role: PRINCIPAL_INVESTIGATOR
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