Alendronate for Prevention of AntiRetroviral Therapy-associated Bone Loss

Bone Demineralization Clinical Trial

— APART  

Official title:

A Multi-centre, Prospective, Randomised Trial of Short Course Alendronate Therapy or Placebo Combined With Vitamin D and Calcium to Prevent Loss of Bone Mineral Density in Antiretroviral-naïve, HIV-1 Infected Subjects Initiating Antiretroviral Therapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02322099
• Other study ID #: APART_2014
• Status: Terminated
• Phase: Phase 4
• Start date: May 2016
• Est. completion date: September 2019

Study information

• Verified date: May 2022
• Source: University College Dublin
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 53
• Est. completion date: September 2019
• Est. primary completion date: September 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bone Demineralization

Intervention

Drug:
• Alendronate
alendronate 70 mg tablets to be administered weekly for a total of 14 weeks, commencing 2 weeks prior to ART initiation
• Placebo
Sugar pill manufactured to mimic alendronate 70 mg tablet administered weekly for a total of 14 weeks, commencing 2 weeks prior to ART

Dietary Supplement:
• calcium carbonate and colecalciferol
Calcium carbonate 1250 mg (equivalent to 500 mg of elemental calcium) and colecalciferol 400 iu (equivalent to 10 micrograms of vitamin D3) tablets administered twice daily for a total of 14 weeks, commencing 2 weeks prior to ART initiation

Drug:
• Tenofovir disoproxil
Emtricitabine / tenofovir disoproxil fumarate 200 / 300 mg tablet administered once-daily with food (open-label) commencing 2 weeks after alendronate initiation and continuing for 48 weeks

Locations

Country	Name	City	State
Ireland	Beaumont Hospital	Dublin
Ireland	Mater Misericordiae University Hospital	Dublin

Sponsors (6)

Lead Sponsor	Collaborator
University College Dublin	Beaumont Hospital, Health Research Board, Ireland, Mater Misericordiae University Hospital, Royal College of Surgeons, Ireland, Rush University Medical Center

Country where clinical trial is conducted

Ireland, 

References & Publications (2)

Cotter AG, Sabin CA, Simelane S, Macken A, Kavanagh E, Brady JJ, McCarthy G, Compston J, Mallon PW; HIV UPBEAT Study Group. Relative contribution of HIV infection, demographics and body mass index to bone mineral density. AIDS. 2014 Sep 10;28(14):2051-60. doi: 10.1097/QAD.0000000000000353. — View Citation

McComsey GA, Kendall MA, Tebas P, Swindells S, Hogg E, Alston-Smith B, Suckow C, Gopalakrishnan G, Benson C, Wohl DA. Alendronate with calcium and vitamin D supplementation is safe and effective for the treatment of decreased bone mineral density in HIV. AIDS. 2007 Nov 30;21(18):2473-82. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pathogenesis of BMD loss with initiation of ART	Relationship between changes in T-cell and B-cell subsets, bone turnover and BMD with ART initiation	50 weeks
Primary	Rate of changes in bone mineral density	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	50 weeks
Secondary	Rate of changes in bone turnover markers	Between-group differences in percentage change in bone turnover markers	50 weeks
Secondary	Impact of ART choice on alendronate protective effect	Impact of choice of ART on changes in BMD and bone turnover markers	50 weeks