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-GB

Lead Sponsor: niversity College Dublin

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

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 previous 12 months to enrollment)
•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: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
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 GFR<60mls/min/1.73m2)
•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-gastrointestinal 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
•hepatitis B (sAg positive) or 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.
•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

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