Alendronate for Prevention of AntiRetroviral Therapy-associated Bone Loss

Phase 4

Terminated

• Conditions: Bone Demineralization
• Interventions: Drug: Alendronate; Drug: Placebo; Dietary Supplement: calcium carbonate and colecalciferol; Drug: Tenofovir disoproxil

• Registration Number: NCT02322099
• Lead Sponsor: University College Dublin

Brief Summary

Antiretroviral therapy (ART) initiation is associated with a significant loss of bone mineral density (BMD), characterised by increases in bone turnover, which is largely limited to the first 48 weeks of therapy. Bisphosphonates, such as alendronate, decrease bone turnover and can limit loss of bone mineral density.

This study aims to determine if a short course of treatment with the oral bisphosphonate alendronate can limit loss of bone mineral density associated with initiation of ART in HIV-1 infected, antiretroviral naive, adult subjects.

Detailed Description

Multi-centre, prospective, randomised, double-blind, placebo-controlled trial over 50 weeks. The aims of this study include:

1. To determine if short-course treatment with alendronate versus placebo combined with calcium and vitamin D, initiated 2 weeks prior to start of ART and can prevent loss of BMD over 48 weeks of follow-up post ART initiation.

2. To explore the effect of alendronate on bone turnover in the setting of ART initiation.

3. To determine which factors, such as choice of ART, impacts the protective effect of alendronate in preventing BMD loss.

4. To determine the relationship between changes in bone turnover markers, vitamin D, parathyroid hormone and calcium levels.

5. To explore the pathogenesis of BMD loss with initiation of ART by investigating relationships between changes in immune function (T-cells and B-cells subsets), bone turnover and BMD.

Study Timeline

• Study First Submitted: 2014-12-17
• Study First Submitted QC: 2014-12-17
• Study First Posted: 2014-12-22
• Study Start: 2016-05
• Primary Completion: 2019-09
• Study Completion: 2019-09
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-20
• Last Update Posted: 2022-05-26

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 53

Inclusion Criteria

• male>30 years old or female>35 years old
• HIV-1 antibody positive
• antiretroviral therapy naïve
• be presumed to have achieved peak bone mass
• be eligible for initiation of antiretroviral therapy in the opinion of the investigator
• be able to provide written, informed consent

Exclusion Criteria

• subjects unable to comply with the study protocol or unable to stand/sit upright for at least 30 minutes
• history of osteoporosis
• history of fragility fracture or previous femoral fracture
• chronic renal failure
• hypocalcemia or hypercalcemia at screening
• history of Paget's disease or known primary hyperparathyroidism
• previous treatment with or allergy (including hypersensitivity) to bisphosphonates
• recent history (past 12 months) of peptic or duodenal ulcers or oesophagitis, aspiration or any other abnormality of the oesophagus
• current therapy with prescribed calcium or vitamin D preparations (other than over-the-counter multivitamin preparations)
• current therapy with aspirin or other regularly prescribed non-steroidal anti-inflammatory drugs
• recent dental work (within the past 3 months) or poor oral hygiene (as judged in the opinion of the investigator)
• recent (within the past three months) significant steroid exposure
• for female subjects: pregnancy at screening, planning future pregnancies or unwilling to take measures to avoid pregnancy for the duration of the study
• where in the investigator's opinion, there is a necessity to initiate ART within the pre-ART study window period
• hepatitis B or hepatitis C co-infection
• any active illness (including AIDS illness) which in the opinion of the investigator precludes participation in the study
• subjects concurrently enrolled in another clinical trial of an investigational medical product

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Alendronate	Alendronate	Alendronate 70 mg plus calcium/vitamin D (1250 mg/400iu) plus Truvada®
Alendronate	calcium carbonate and colecalciferol	Alendronate 70 mg plus calcium/vitamin D (1250 mg/400iu) plus Truvada®
Placebo	Placebo	Placebo to alendronate 70mg plus calcium/vitamin D (1250 mg/400iu) plus Truvada®
Placebo	calcium carbonate and colecalciferol	Placebo to alendronate 70mg plus calcium/vitamin D (1250 mg/400iu) plus Truvada®
Alendronate	Tenofovir disoproxil	Alendronate 70 mg plus calcium/vitamin D (1250 mg/400iu) plus Truvada®
Placebo	Tenofovir disoproxil	Placebo to alendronate 70mg plus calcium/vitamin D (1250 mg/400iu) plus Truvada®

Primary Outcome Measures

Name	Time	Method
Rate of changes in bone mineral density	50 weeks	Between-group differences in percentage change in total hip, lumbar spine, femoral neck BMD and body composition to week 50 among subjects who received at least one dose of the study medication

Secondary Outcome Measures

Name	Time	Method
Rate of changes in bone turnover markers	50 weeks	Between-group differences in percentage change in bone turnover markers
Impact of ART choice on alendronate protective effect	50 weeks	Impact of choice of ART on changes in BMD and bone turnover markers

Trial Locations

Locations (2)

Beaumont Hospital; 🇮🇪 Dublin, Ireland

Mater Misericordiae University Hospital; 🇮🇪 Dublin, Ireland