Bone Antiresorptive Therapy With Antiretroviral Initiation (BATARI) Pilot Trial (BATARI)

This is a two-site, three-arm, open-label, pilot randomized controlled trial of bone anti-resorptive therapy during ART initiation in HIV-infected adults. Thirty (30) treatment-naïve HIV-infected adults initiating eligible first-line ART regimens will be randomized in a 1:1:1 fashion to one of the following three arms:

1. no bone anti-resorptive therapy (standard of care)
2. concomitant initiation of a 24 week course of co-formulated alendronate/vitamin D;
3. a 24 week delay in initiation of a 24 week course of alendronate/vitamin D

Assessments (including clinical evaluation, questionnaires, adherence, basic laboratory evaluation, and BMD measurement) will be performed at baseline, 24 and 48 weeks. The primary objective will involve calculation of σ and ρ using all data; δ will be estimated by comparing the two alendronate arms pooled to the no-treatment arm.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: alendronate/vitamin D

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M5G 2N2
      • Toronto General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Documented HIV-1 infection
• Adult (aged >18 years or as per local guidelines)
• Premenopausal, if female
• Antiretroviral-naïve
• Starting first-line ART including tenofovir/emtricitabine with either efavirenz (co-formulated as Atripla®) or elvitegravir, cobicistat (co-formulated as Stribild®)
• Low (<10%) ten-year fracture risk as assessed by the FRAX score validated for Canadian populations

Exclusion Criteria:

• Presence of established osteoporosis at baseline as determined by BMD measurement
• Prior or current use of any bone anti-resorptive therapy (eg. bisphosphonate, estrogens with the exception of oral contraceptive pills, etc.)
• Inability to communicate in English
• Creatinine clearance <35 mL/min (using Cockcroft-Gault formula)
• Hypersensitivity to alendronate, other bisphosphonates, or any component of the formulation
• Hypocalcemia
• Abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia
• Inability to stand or sit upright for at least 30 minutes
• Pregnancy, active plans to become pregnant, or lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: no bone anti-resorptive therapy; (standard of care)
Experimental: 24-week tx of alendronate/vitamin D; Concomitant initiation of a 24 week course of co-formulated alendronate/vitamin D	Drug: alendronate/vitamin D; once weekly 70mg oral dose of alendronate co-formulated with 5600IU vitamin D3 (cholecalciferol) for 24 weeks.; Other Names: Fosavance 70/56
Experimental: Delayed 24-week tx of alendronate/vitamin D; a 24 week delay in initiation of a 24 week course of alendronate/vitamin D	Drug: alendronate/vitamin D; once weekly 70mg oral dose of alendronate co-formulated with 5600IU vitamin D3 (cholecalciferol) for 24 weeks.; Other Names: Fosavance 70/56

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage changes in BMD at a) the lumbar spine and b) proximal femur	The primary analysis will compare the percentage changes in BMD for the two alendronate/vitamin D arms pooled against the control arm.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility	The proportion of patients who are eligible and who consent to participate will be calculated, and the timeliness (rate) of enrollment will be described, to further inform the feasibility of a larger randomized controlled trial.	48 weeks
Acceptability	Using standardized questions, participants will be asked about the acceptability of the alendronate therapy (including the experience of pill-taking and the weekly schedule)	48 weeks
Safety/Tolerability	As per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events.	48 weeks
Adherence	Adherence with anti-resorptive therapy will be assessed by pill count and questionnaire.	48 weeks
Bone Biomarkers	Two bone biomarkers will be assessed: cross-linked carboxyterminal-telopeptide (CTX) and aminoterminal propeptide of type 1 collagen (P1NP).	48 weeks

Collaborators and Investigators

• Sponsor: Unity Health Toronto
• Collaborators: CIHR Canadian HIV Trials Network
• Investigators: Principal Investigator: Darrell Tan, MD, Unity Health Toronto

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2014
• Primary Completion (Actual): March 19, 2018
• Study Completion (Actual): March 19, 2018

Study Registration Dates

• First Submitted: October 9, 2013
• First Submitted That Met QC Criteria: October 18, 2013
• First Posted (Estimate): October 24, 2013

Study Record Updates

• Last Update Posted (Actual): April 19, 2018
• Last Update Submitted That Met QC Criteria: April 17, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: HIV; osteoporosis; vitamin D; alendronate; bone Mineral Density
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D; Alendronate
• Other Study ID Numbers: CTNPT 021