Clinical trial NCT02322099: Alendronate for Prevention of AntiRetroviral Therapy-associated Bone Loss
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Bone Demineralization
Keywords: human immunodeficiency virus
bone diseases
osteopenia
osteoporosis
fracture
bone turnover
alendronate
antiretroviral
Lead sponsor: University College Dublin
Sponsor class: OTHER
Collaborators: name: Health Research Board, Ireland
name: Royal College of Surgeons, Ireland
name: Mater Misericordiae University Hospital
name: Beaumont Hospital
name: Rush University Medical Center
First posted: 2014-12-22
Enrollment: 53
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of changes in bone mineral density
timeFrame: 50 weeks
Secondary outcomes:
measure: Rate of changes in bone turnover markers
timeFrame: 50 weeks
measure: Impact of ART choice on alendronate protective effect
timeFrame: 50 weeks
Other outcomes:
measure: Pathogenesis of BMD loss with initiation of ART
timeFrame: 50 weeks
Locations:
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Dublin
country: Ireland
facility: Beaumont Hospital
Study officials:
affiliation: University College Dublin
name: Patrick WG Mallon, MB BCh BAO,PhD,FRCPI
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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. doi: 10.1097/QAD.0b013e3282ef961d.