Clinical trial NCT05527548: A Single-blind RCT to Investigate the Effect of Alendronate on Knee Function Following ACLR
Official title: The Effect of Oral Administration of Alendronate on Knee Functions Following Anterior Cruciate Ligament Reconstruction - A Pilot Study of Single-Blind Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: ACL Reconstruction
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2022-09-02
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Anterior cruciate ligament (ACL) is the key ligament connecting the femur to tibia that helps stabilising the knee joint. ACL tear is common. It accounts for over 50% of all knee injuries and affects more than 200,000 people in the United States each year. Patients with ACL tear have a higher risk of developing post-traumatic osteoarthritis. ACL reconstruction (ACLR) with the attachment of tendon grafts within bone tunnels are commonly performed to restore the stability of the joint and thereby minimise injury to both the chondral surface and surrounding tissues. About 130,000 ACLR was performed in the United States in 2006. Both the incidence rates of ACL injuries and ACLR are on the rise, particularly in children and adolescents. Conventional ACLR is not a universally successful procedure, with long healing time and high rates of graft failure (2.8%) and graft laxity (18%). The average cost of an ACLR in the United States was about USD 24,707 ±15,644. The cost for revision surgery and societal cost due to absence from work and sport are expected to be even higher. The demand for a better intervention to improve the outcomes after ACLR and reduce the healing time is huge.

ALN was chosen for the pilot study because it is the most studied BPs, with high bone-binding affinity and more prolonged duration of action. As a member of amino BPs, it also has higher anti-resorptive activities compared to non-amino BPs. Our encouraging results on ALN in the animal studies also provide evidence to support the trial of ALN in human.

ALN have been shown to have a very good safety and tolerability profile. The common side effects of ALN are stomach pain, constipation, diarrhoea, gas, or nausea. Oral ALN seems can induce mild gastro-intestinal disturbances. However, two studies, with subjects treated with ALN for 10 months and 2.9 years, respectively, showed that ALN was not associated with any increased incidence of upper GI tract events. The serious adverse event, oesophageal cancer, has been associated with ALN. However, two published papers with long term observations of 9 and 4.5 years, respectively, showed that ALN was not significantly associated with incident oesophageal or gastric cancer compared with the control group.

This study aims to evaluate the effects of oral administration of ALN on knee stability (primary), peri-tunnel bone loss, tunnel bone formation, knee laxity, knee muscle strength as well as self-reported knee symptoms, function and sports activity over 12 months in patients undergoing ACLR in a pilot study of single-blind randomised controlled trial.


Eligibility criteria: Inclusion Criteria:

* Male and female with age 18-40 at the time of surgery
* First ACLR
* Single leg involvement
* Able to attend pre-operative assessment
* Voluntarily agreed to participate and signed the informed consent form

Exclusion Criteria:

* Known chronic disease or receiving long-term medications affecting bone metabolism including BPs
* Contraindication to alendronate therapy such as poor dental fitness
* ACL injury less than 6 weeks
* Injury on duty cases
* Patients who have undergone arthroscopy or open surgery in the index knee in the last 12 months
* Other associated injuries (fractures and other ligament involvement such as neurovascular bundles injury)
* Chondral lesion with concomitant intervention
* Presence of X-ray features of osteoarthritis including decrease in joint space, presence of osteophytes and subchondral cysts
* Neurological deficit
* Pregnant or breastfeeding
* Inability to give informed consent

Primary outcomes:
measure: Single-leg Hop Test (SLH)
timeFrame: Change from baseline SLH at 8 weeks
measure: Single-leg Hop Test (SLH)
timeFrame: Change from baseline SLH at 2 months
measure: Single-leg Hop Test (SLH)
timeFrame: Change from baseline SLH at 4 months
measure: Single-leg Hop Test (SLH)
timeFrame: Change from baseline SLH at 10 months
Secondary outcomes:
Other outcomes:
Locations:
city: Sha Tin
country: Hong Kong
facility: Prince of Wales Hospital
Study officials:
References: