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

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

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.

Study Overview

• Status: Unknown
• Conditions: HIV Infections

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

• Study Contact: Name: Sarah Pett, MD; Phone Number: +44 203 108 2103; Email: s.pett@ucl.ac.uk
• Study Contact Backup: Name: Amelia Moore, MD; Phone Number: +44 207 188 4092; Email: amelia.moore@kcl.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, WC1E 6JB
    • Recruiting
    • Mortimer Market Centre
    • Contact: Sarah Pett, MD; Email: s.pett@ucl.ac.uk
    • Contact: Andrea Cartier; Email: a.cartier@ucl.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Probability Sample

Study Population

HIV-1-infected men aged ≥40 years on ART regimen containing rilpivirine/tenofovir disoproxil fumarate/ emtricitabine for at least 6 months.

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: King's College London

Publications and helpful links

General Publications

• Frost ML, Cook GJ, Blake GM, Marsden PK, Benatar NA, Fogelman I. A prospective study of risedronate on regional bone metabolism and blood flow at the lumbar spine measured by 18F-fluoride positron emission tomography. J Bone Miner Res. 2003 Dec;18(12):2215-22. doi: 10.1359/jbmr.2003.18.12.2215.
• Cassetti I, Madruga JV, Suleiman JM, Etzel A, Zhong L, Cheng AK, Enejosa J; Study 903E Team*. The safety and efficacy of tenofovir DF in combination with lamivudine and efavirenz through 6 years in antiretroviral-naive HIV-1-infected patients. HIV Clin Trials. 2007 May-Jun;8(3):164-72. doi: 10.1310/hct0803-164.
• Cook GJ, Lodge MA, Blake GM, Marsden PK, Fogelman I. Differences in skeletal kinetics between vertebral and humeral bone measured by 18F-fluoride positron emission tomography in postmenopausal women. J Bone Miner Res. 2000 Apr;15(4):763-9. doi: 10.1359/jbmr.2000.15.4.763.
• Frost ML, Cook GJ, Blake GM, Marsden PK, Fogelman I. The relationship between regional bone turnover measured using 18F-fluoride positron emission tomography and changes in BMD is equivalent to that seen for biochemical markers of bone turnover. J Clin Densitom. 2007 Jan-Mar;10(1):46-54. doi: 10.1016/j.jocd.2006.10.006. Epub 2006 Dec 27.

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2018
• Primary Completion (Anticipated): November 1, 2019
• Study Completion (Anticipated): January 1, 2020

Study Registration Dates

• First Submitted: April 25, 2017
• First Submitted That Met QC Criteria: January 12, 2018
• First Posted (Actual): January 19, 2018

Study Record Updates

• Last Update Posted (Actual): July 30, 2018
• Last Update Submitted That Met QC Criteria: July 26, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: 16/0657

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No