Altering Bone Microarchitecture and Mechanics by Off-label Pharmaceutical Intervention Following an Acute Knee Injury (ZAPOA)

University of Calgary

Status and phase: Terminated; Phase 1

Conditions: Anterior Cruciate Ligament Injuries; Anterior Cruciate Ligament Tear; Anterior Cruciate Ligament Rupture; Osteo Arthritis Knee

Treatments: Drug: Placebo; Drug: Zoledronic Acid Injection

Study type: Interventional

Funder types: Other

Identifiers

NCT05204836

REB21-1109

Details and patient eligibility

About

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.

Full 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.

Enrollment: 4 patients

Sex: All

Ages: 25 to 45 years old

Volunteers: No Healthy Volunteers

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 (2.10-2.60 mmol/L) and a creatinine level above 59 (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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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4 participants in 2 patient groups, including a placebo group

Zoledronic Acid Injection

Experimental group

Description:

Participants will receive 1 dose of 5 mg/100 mL intravenous zoledronic acid

Treatment:

Drug: Zoledronic Acid Injection

Placebo

Placebo Comparator group

Description:

Participants will receive 1 dose 100 ml Saline.

Treatment:

Drug: Placebo