Alendronate for Prevention of antiretroviral therapy-associated bone loss.

Phase 1

Conditions: Human immunodeficiency virus (HIV) infection
MedDRA version: 20.1Level: PTClassification code 10020161Term: HIV infectionSystem Organ Class: 10021881 - Infections and infestations
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: EUCTR2014-004819-37-DK

Lead Sponsor: niversity College Dublin

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 80

Inclusion Criteria

- male>25 years old or female>30 years old
- HIV-1 antibody positive (no CD4 or HIV RNA criteria)
- antiretroviral therapy naïve* (not having had suppressive ART in the prior 12 months)
- be presumed to have achieved peak bone mass
- eligible for initiation of antiretroviral therapy in the opinion of the investigator
- able to provide written informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

- Subjects unable to comply with the study protocol or unable to stand/sit upright for at least 30 minutes
- history of osteoporosis (defined as hip, femoral neck or spine T score of <-2.5 in men over age >50 or in post-menopausal women)
- history of fragility fracture or previous femoral fracture
- chronic renal failure estimated by eGFR<60mls/min/1.73m2 at screening using the abbreviated Modification of Diet in Renal Disease (MDRD) equation:
- eGFR (ml/min/1,73 m2) = 175 x (CrS) -1,154 x (age)-0,203 x 0,742 (if female) x 1,21 (if black)
- hypocalcaemia (corrected calcium <2.2mmol/L) or hypercalcaemia (>2.6mmol/L) 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 upper gastro-intestinal problem or oesophageal disease that in the opinion of the investigator precludes the use of alendronate
- history of dental disease, periodontal disease, poor oral hygiene (as judged in the opinion of the investigator) or recent invasive dental procedures (within the past 3 months) comprising dental extraction and dental prosthetic
- 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 significant steroid exposure defined as continual or cumulative use of >5mg prednisolone daily or equivalent for = three months, as per EACS guidelines
- for female subjects: pregnancy or breastfeeding 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 (i.e. within the period between screening and ART initiation (approximately 3 weeks)
- subjects with active hepatitis B infection (defined as hepatitis B sAg positive) or hepatitis C (defined as hepatitis C Ab and RNA positive) co-infection
- any active illness (including AIDS-defining illness) which in the opinion of the investigator precludes participation in the study
- cancer or receiving chemotherapy or radiotherapy
- subjects concurrently enrolled in another clinical trial of an investigational medical product

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: In antiretroviral-naïve, HIV1-infected adults, to compare the effect of a short (14 week) course of oral alendronate 70mg weekly versus placebo combined with calcium and vitamin D, initiated 2 weeks prior to start of antiretroviral therapy (ART) for HIV1 infection on ART-induced bone mineral density (BMD) loss over 48 weeks of follow-up post ART initiation. ;Secondary Objective: To explore the effect of alendronate on bone turnover in HIV-1 infected subjects initiating ART. <br>To determine which factors, such as choice of ART, impacts the protective effect of alendronate in preventing BMD loss.<br>To investigate relationships between ART-induced changes in immune function, inflammation, bone metabolism and BMD.<br>;Primary end point(s): Between-group difference in percentage change in total hip BMD from baseline to week 50 among subjects who received at least one dose of study medication.;Timepoint(s) of evaluation of this end point: Baseline and week 50

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Between-group differences in percentage change in lumbar spine, femoral neck BMD and body composition to week 50. <br>Between-group differences in percentage change in total hip, lumbar spine and femoral neck BMD to weeks 14 and 26. <br>Between-group differences in percentage change in bone turnover markers to weeks 26 and 50. <br>Between-group differences in percentage change in 25(OH)D, PTH and calcium to week 50. <br>Between-group differences in ART-induced changes immune function, BMD and bone turnover to week 14 and 50.<br>Between-group differences in measures of safety.<br>;Timepoint(s) of evaluation of this end point: Baseline, week 14, week 26 and week 50