Regional Bone Turnover Using 18F-fluoride-PET/CT in HIV-1-infected Men: PETRAM Study

Study Overview
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Brief Summary
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This is a 48 week study to explore the pathogenesis of HIV treatment related bone disease by using a novel imaging technique, 18F-Fluoride Positron Emission Tomography (18F-PET/CT), which measures regional bone formation. The study will include other standard methods (serum bone markers and DXA) for comparison. Patients enrolled will have baseline, week 24 and week 48 assessment, with baseline being the date of replacing tenofovir disoproxil fumarate (TDF) in their HIV treatment regimen with tenofavir alafenamide fumarate (TAF), compared to a control group continuing TDF. Allocation to change to TAF or continue TDF will be randomised to allow an unbiased assessment of bone changes.

Detailed Description
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Study Design: This is an observational, open-label, non-randomised, single centre, 48-week study to explore the utility of a novel scanning platform exploring bone turnover during an immediate or deferred (for 48 weeks) switch from Eviplera® to Odefsey® in HIV-1 infected men aged 40 years or older, and stable on Eviplera®. Participants: HIV-1-infected males, aged ≥40 years, on Eviplera® >24 weeks, with plasma HIV RNA (pVL) <50cp/mL and without any known history of osteoporosis. Groups to be Compared: 1. HIV-1-infected males aged ≥40, stable on Eviplera® (rilpivirine (RPV)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF)) and remaining on EvipleraÒ for 48 weeks on study; 2. HIV-1-infected males aged ≥40 years, switched to Odefsey® (RPV/FTC/tenofovir alafenamide (TAF)) at study enrollment. Study Hypothesis: We hypothesis that there will be ongoing subclinical loss of bone at the hip and lumbar spine as measured by 18F-fluoride-PET/CT in those remaining of Eviplera®, and in those switching to Odefsey® there will be reversal of some of this subclinical loss at 24 and 48 weeks post switch. Primary Outcome Measure(s):To determine the change in regional bone formation at the hip and lumbar spine as measured by 18F-fluoride-PET/CT at 24 weeks post switch from Eviplera® to Odefsey®. Secondary Outcome Measure(s): 1. Change in regional bone formation at the hip and lumbar spine as measured by 18F-fluoride-PET/CT at 48 weeks post switch from Eviplera® to Odefsey®; 2. Assess safety and tolerability of switching to Odefsey®; 3. To compare DXA changes at the hip and lumbar spine to those detected on 18F-fluoride-PET/CT; 4. Measure changes in plasma/serum bone biomarkers over 24 and 48 weeks; 5. To measure the changes in FRAX® score at week 48.

Official Title
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Understanding Changes in Treatment-related Regional Bone Turnover Using 18F-fluoride-PET/CT in HIV-1-infected Men: PETRAM Study

Conditions
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HIV Infections

Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA HIV-1-infected men aged ≥40 years; Virologically suppressed (<50 cp/mL) on Eviplera® for >24 weeks; No known history of osteoporosis (defined as a T-score > -2.5 at the lumbar spine, femoral neck or total hip using DXA); Willing to switch immediately to OdefseyÒ or remain on EvipleraÒ for the duration of the study; No immediate toxicity reason in the opinion of the investigator to switch away from Eviplera; Willing to comply with study procedures. EXCLUSION CRITERIA Contraindication to the receipt of TAF; Contraindication to 18F-fluoride-PET/CT scanning; Anticipated to require additional radiological imaging during the 48 weeks of study participation with a total cumulative radiation dose of >50 millisieverts (mSv); Current or previous treatment (within the prior 12 months) which can affect bone metabolism including systemic corticosteroids for >4 weeks and bisphosphonates; Hepatitis C coinfected.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in regional bone formation at the hip and lumbar spine as measured by 18F-PET/CT at 24 weeks. | Regions of interest will be applied to various regions within the hip including but are not limited to the femoral neck, intertrochanteric region, trochanter and total proximal femur. Further regions of interest will be applied to each vertebral body, skull, pelvis and femoral shaft using the static scan for the calculation of standardised uptake values (SUV). At week 24 | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in regional bone formation at the hip and lumbar spine as measured by 18F-PET/CT at 48 weeks in patients starting a TAF-based ART regimen | Regions of interest will be applied to various regions within the hip including but are not limited to the femoral neck, intertrochanteric region, trochanter and total proximal femur. Further regions of interest will be applied to each vertebral body, skull, pelvis and femoral shaft using the static scan for the calculation of standardised uptake values (SUV). measured by 18F-PET/CT at 48 weeks | 48 weeks | 
| Bone mineral density at the hip and lumbar spine measured by DXA vs. 18F-PET/CT; | Regions of interest will be applied to including but not limited to the femoral neck, intertrochanteric region, total hip, each lumbar vertebral body, and upper femoral shaft for the calculation of Ki which reflects regional bone perfusion and bone turnover and will be compared to results obtained Dual-energy x-ray absorptiometry (DXA) scans will be performed at baseline (Visit 1b), weeks 24 (Visit 2b) and 48 (Visit 3b) to evaluate the change in areal bone mineral density (BMD) (in g/cm2) in response to treatment at the lumbar spine (L1-L4), total hip, femoral neck and whole body using standard protocols. | 24 and 48 weeks | 
| The changes in bone biomarkers over 24 and 48 weeks with changes in 18F-PET/CT; | Regions of interest will be applied to including but not limited to the femoral neck, intertrochanteric region, total hip, each lumbar vertebral body, and upper femoral shaft for the calculation of Ki which reflects regional bone perfusion and bone turnover, with changes in bone biomarkers. The bone markers to be analysed include, but are not limited to, procollagen Type I N terminal propeptide (PINP), and cross-linked C telopeptides of Type I collagen (CTX). | 24 and 48 weeks |