Zoledronic Acid for Anterior Cruciate Ligament Injury

(ZAPOA Trial)

Overseen By Steven Boyd, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Calgary

Must not be taking: Bisphosphonates

Disqualifiers: Pregnancy, Renal impairment, Bone disease, others

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether an injection of zoledronic acid can slow joint damage after an ACL (anterior cruciate ligament) injury. Researchers aim to determine if this treatment is more effective than a placebo, an inactive substance. It suits individuals who have recently experienced a complete ACL tear and do not have other serious knee injuries or certain medical conditions. Participants should also have normal calcium levels and good kidney function. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are already taking another bisphosphonate (a type of medication for bone conditions), you cannot participate in this study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that zoledronic acid, the treatment being tested, has produced mixed results in other studies. For instance, one study suggested that early use of zoledronic acid could help prevent bone damage after an injury. However, another study found it might weaken the connection between tendons and bones, reducing their strength and stiffness. In a different small study, zoledronic acid helped reduce knee pain and bone problems over six months. As this is a phase 1 trial, the main goal is to determine the treatment's safety for people. Researchers are still learning about its tolerability and potential side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using zoledronic acid for anterior cruciate ligament (ACL) injuries because it offers a novel approach compared to the usual surgical and rehabilitation options. Unlike traditional treatments that focus on mechanical repair and physical therapy, zoledronic acid is a medication typically used to strengthen bones and may enhance the healing process of the ACL by preventing bone loss. This unique mechanism of action could potentially improve recovery outcomes and provide an innovative solution for patients with ACL injuries.

What evidence suggests that zoledronic acid injection might be an effective treatment for ACL injury?

Research suggests that zoledronic acid, which participants in this trial may receive, might help manage joint damage after an ACL injury. Studies have shown that starting treatment early with zoledronic acid can prevent changes in the bone under the cartilage, potentially slowing joint wear and tear. In a small study, zoledronic acid reduced knee pain and the size of bone marrow lesions in patients over six months. However, some research indicates that zoledronic acid might slow the healing of tendons to bones. These findings are promising, but the effects of the treatment are still under investigation. Participants in this trial may also receive a placebo as part of the study's design. ^{2 3 4 5 6}

Who Is on the Research Team?

Steven Boyd, PhD

Principal Investigator

University of Calgary

Gregory Kline, MD

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

This trial is for adults with a recent, complete tear in their anterior cruciate ligament (ACL) who have normal calcium and kidney function. They can have other knee injuries too but shouldn't be pregnant or planning pregnancy soon, have past knee injuries, or conditions affecting bone turnover.

Inclusion Criteria

I have injuries to my knee's ligaments or meniscus.

I can fully straighten my knee when it's supported.

I have a completely torn ACL in one knee.

Exclusion Criteria

Pregnant and nursing mothers

I have severe kidney problems or my kidneys are not working well right now.

I have had previous knee injuries, including ligament or meniscus tears, or fractures within the joint.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a zoledronic acid injection at baseline

1 day

1 visit (in-person)

Monitoring

Participants are monitored radiographically with HR-pQCT, DECT, X-Ray, EOS, and MRI to assess joint changes and effects of zoledronic acid

18 months

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Zoledronic Acid Injection

Trial Overview The study tests if an injection of zoledronic acid can prevent joint damage after an ACL injury compared to a placebo. Participants will receive either the real drug or a placebo without knowing which one they get.

How Is the Trial Designed?

Group I: Zoledronic Acid Injection Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

Participants will receive 1 dose 100 ml Saline.

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36464243/

Early zoledronate treatment inhibits subchondral bone ... Findings from this study suggest that early inhibition of bone resorption by bisphosphonate after injury may be a promising therapeutic approach ...

2. withpower.com withpower.com/trial/phase-1-osteoarthritis-knee-1-2022-c9681

Zoledronic Acid for Anterior Cruciate Ligament Injury Trial Overview The study tests if an injection of zoledronic acid can prevent joint damage after an ACL injury compared to a placebo. Participants will receive ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6055777/

Negative effect of zoledronic acid on tendon-to-bone healing ZA treatment resulted in 19% (95% CI 5–33%) lower pullout strength and 43% (95% CI 14–72%) lower stiffness of the tendon–bone interface, compared with control ( ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S8756328222003155

Early zoledronate treatment inhibits subchondral bone ... Full Length Article. Early zoledronate treatment inhibits subchondral bone microstructural changes in skeletally-mature, ACL-transected canine knees.

5. bmcmusculoskeletdisord.biomedcentral.com bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/s12891-018-2143-2

A protocol for a multicentre, randomised, double-blind ... In a pilot study, we demonstrated that zoledronic acid reduced knee pain and size of subchondral bone marrow lesions (BMLs) over 6 months in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05204836

Altering Bone Microarchitecture and Mechanics by Off ... 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 ...