Alendronate for Prevention of AntiRetroviral Therapy-associated Bone Loss

NCT02322099 | Terminated Phase 4 DMC

• 1 other identifier: APART_2014
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 2

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.

Conditions

Bone Demineralization

Keywords

human immunodeficiency virus; bone diseases; osteopenia; osteoporosis; fracture; bone turnover; alendronate; antiretroviral

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Rate of changes in bone turnover markers

  50 weeks

• Impact of ART choice on alendronate protective effect

  50 weeks

Other Outcomes (1)

• Pathogenesis of BMD loss with initiation of ART

  50 weeks

Study Arms (2)

Alendronate

ACTIVE COMPARATOR

Alendronate 70 mg plus calcium/vitamin D (1250 mg/400iu) plus Truvada®

Drug: Alendronate; Dietary Supplement: calcium carbonate and colecalciferol; Drug: Tenofovir disoproxil

Placebo

PLACEBO COMPARATOR

Placebo to alendronate 70mg plus calcium/vitamin D (1250 mg/400iu) plus Truvada®

Drug: Placebo; Dietary Supplement: calcium carbonate and colecalciferol; Drug: Tenofovir disoproxil

Interventions

Alendronate DRUG

alendronate 70 mg tablets to be administered weekly for a total of 14 weeks, commencing 2 weeks prior to ART initiation

Also known as: Fosamax, Romax

Alendronate

Placebo DRUG

Sugar pill manufactured to mimic alendronate 70 mg tablet administered weekly for a total of 14 weeks, commencing 2 weeks prior to ART

Placebo

calcium carbonate and colecalciferol DIETARY_SUPPLEMENT

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

Also known as: Calcichew D3 forte, Ideos

Alendronate; Placebo

Tenofovir disoproxil DRUG

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

Also known as: Truvada

Alendronate; Placebo

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University College Dublin: lead
• Health Research Board, Ireland: collaborator
• Royal College of Surgeons, Ireland: collaborator
• Mater Misericordiae University Hospital: collaborator
• Beaumont Hospital: collaborator
• Rush University Medical Center: collaborator

Study Sites (2)

Mater Misericordiae University Hospital

Dublin, 7, Ireland

Location

Beaumont Hospital

Dublin, 9, Ireland

Location

Related 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.

  PMID: 25265073 BACKGROUND

• 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.

  PMID: 18025884 BACKGROUND

MeSH Terms

Conditions

Bone Demineralization, Pathologic; Acquired Immunodeficiency Syndrome; Bone Diseases; Bone Diseases, Metabolic; Osteoporosis; Fractures, Bone

Interventions

Alendronate; Calcium Carbonate; Cholecalciferol; Tenofovir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Calcium Compounds; Inorganic Chemicals; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Minerals; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Patrick WG Mallon, MB BCh BAO,PhD,FRCPI

  University College Dublin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 17, 2014
• First Posted: December 22, 2014
• Study Start: May 1, 2016
• Primary Completion: September 1, 2019
• Study Completion: September 1, 2019
• Last Updated: May 26, 2022

Record last verified: 2022-05

Locations

IE (2)