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Alendronate for Prevention of AntiRetroviral Therapy-associated Bone Loss (APART)

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ClinicalTrials.gov Identifier: NCT02322099
Recruitment Status : Recruiting
First Posted : December 22, 2014
Last Update Posted : September 25, 2019
Sponsor:
Collaborators:
Health Research Board, Ireland
Royal College of Surgeons, Ireland
Mater Misericordiae University Hospital
Beaumont Hospital
Rush University Medical Center
Information provided by (Responsible Party):
Patrick Mallon, 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.


Condition or disease Intervention/treatment Phase
Bone Demineralization Drug: Alendronate Drug: Placebo Dietary Supplement: calcium carbonate and colecalciferol Drug: Tenofovir disoproxil Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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 Start Date : May 2016
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Alendronate
Alendronate 70 mg plus calcium/vitamin D (1250 mg/400iu) plus Truvada®
Drug: Alendronate
alendronate 70 mg tablets to be administered weekly for a total of 14 weeks, commencing 2 weeks prior to ART initiation
Other Names:
  • Fosamax
  • Romax

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
Other Names:
  • Calcichew D3 forte
  • Ideos

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
Other Name: Truvada

Placebo Comparator: Placebo
Placebo to alendronate 70mg plus calcium/vitamin D (1250 mg/400iu) plus Truvada®
Drug: 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
Other Names:
  • Calcichew D3 forte
  • Ideos

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
Other Name: Truvada




Primary Outcome Measures :
  1. Rate of changes in bone mineral density [ Time Frame: 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 :
  1. Rate of changes in bone turnover markers [ Time Frame: 50 weeks ]
    Between-group differences in percentage change in bone turnover markers

  2. Impact of ART choice on alendronate protective effect [ Time Frame: 50 weeks ]
    Impact of choice of ART on changes in BMD and bone turnover markers


Other Outcome Measures:
  1. Pathogenesis of BMD loss with initiation of ART [ Time Frame: 50 weeks ]
    Relationship between changes in T-cell and B-cell subsets, bone turnover and BMD with ART initiation



Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02322099


Contacts
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Contact: Tara McGinty, MB, BCh, BAO tara.mcginty@ucd.ie
Contact: Alan Macken, BA alan.macken@ucd.ie

Locations
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Ireland
Mater Misericordiae University Hospital Recruiting
Dublin, Ireland, 7
Contact: Tara McGinty, MB, BCh, BAO       tara.mcginty@ucd.ie   
Contact: Patrick WG Mallon, MB BCh, PhD, FRCPI       paddy.mallon@ucd.ie   
Sub-Investigator: John Lambert, MD, PhD         
Sub-Investigator: Gerard Sheehan, MB BCh BAO, FRCPI         
Beaumont Hospital Recruiting
Dublin, Ireland, 9
Contact: Samuel McConkey, MB BCh, MD,MRCPI       smcconkey@rcsi.ie   
Contact: Nora McNally, MD         
Sponsors and Collaborators
University College Dublin
Health Research Board, Ireland
Royal College of Surgeons, Ireland
Mater Misericordiae University Hospital
Beaumont Hospital
Rush University Medical Center
Investigators
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Principal Investigator: Patrick WG Mallon, MB BCh BAO,PhD,FRCPI University College Dublin

Additional Information:
Publications:
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Responsible Party: Patrick Mallon, Principal Investigator, University College Dublin
ClinicalTrials.gov Identifier: NCT02322099     History of Changes
Other Study ID Numbers: APART_2014
First Posted: December 22, 2014    Key Record Dates
Last Update Posted: September 25, 2019
Last Verified: September 2019
Keywords provided by Patrick Mallon, University College Dublin:
human immunodeficiency virus
bone diseases
osteopenia
osteoporosis
fracture
bone turnover
alendronate
antiretroviral
Additional relevant MeSH terms:
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Bone Demineralization, Pathologic
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases
Vitamin D
Ergocalciferols
Calcium, Dietary
Alendronate
Cholecalciferol
Vitamins
Tenofovir
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Anti-Retroviral Agents
Calcium Carbonate
Calcium
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Calcium-Regulating Hormones and Agents
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Antacids