Differences in levels of heart fat in people living with HIV and the general population

ISRCTN	ISRCTN47550369
DOI	https://doi.org/10.1186/ISRCTN47550369
IRAS number	337369
Secondary identifying numbers	IRAS 337369

Submission date: 01/02/2024
Registration date: 16/02/2024
Last edited: 16/02/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English Summary

Background and study aims
The present study is designed to investigate differences between people living with HIV (PLWHIV) and general populations in terms of how the body uses and stores energy. Magnetic Resonance Imaging (MRI) is the primary tool employed to measure fat around body organs, including the heart and liver. The fat around body organs, also known as visceral fat, is known to be associated with metabolic syndrome and a risk factor for developing heart attacks and strokes. MRI scans are used frequently in hospitals to diagnose a range of conditions. These scans use radio waves to measure protons in body tissues. The machines can reconstruct tissues using complex algorithms to form composite images of body structures. Medical professionals commonly use MRI scans to evaluate the structure and function of the heart. Specific MRI sequences are employed to assess the integrity of heart muscle, establishing heart MRI as the gold standard imaging technique for heart and heart muscle disease assessment.

In this sub-study, multiple MRI sequences are used to evaluate both the heart and the liver, aiming to identify any changes in their respective fat levels. Furthermore, the study investigates alterations in fat levels within the heart muscle cells while concurrently assessing any changes in the heart's functionality. Individuals living with HIV are noted to have a roughly double risk of heart attacks compared to the general population. Previous studies demonstrate that this elevated risk may be attributed to the unique ways in which fat is stored and metabolized in the bodies of PLWHIV. The anticipation is that this study will provide valuable insights into the reasons behind the increased risk of heart attacks in HIV-positive individuals and shed light on how reducing visceral fat may mitigate this risk. The findings of this study may potentially pave the way for the development of new medicines or treatment strategies aimed at reducing the risk of heart attacks in individuals living with HIV.

Who can participate?
PLWHIV aged 40 years and over

What does the study involve?
This sub-study will use multiple MRI sequences to assess the heart and the liver to investigate any changes in heart and liver fat. In addition, any changes in fat levels within the heart muscle cells will be assessed whilst also looking for any change in the way the heart is functioning.

What are the possible benefits and risks of participating?
MRI scans do not use ionising radiation and there is no risk to undertaking an MRI in terms of radiation.

Where is the study run from?
University of Liverpool

When is the study starting and how long is it expected to run for?
April 2023 to March 2025

Who is funding the study?
British HIV Association

Who is the main contact?
Thomas Heseltine, hezmondo@liverpool.ac.uk

Contact information

Dr Thomas Heseltine
Scientific, Principal Investigator

University of Liverpool
Liverpool
L69 3BX
United Kingdom

ORCID ID	0000-0002-4843-3433
Phone	+44 (0)7920407640
Email	Thomas.heseltine@liverpoolft.nhs.uk

Mrs Karen Jennings-Wilding
Public

University of Liverpool
Liverpool
L69 3BX
United Kingdom

Phone	+44 (0)1517951780
Email	hezmondo@liverpool.ac.uk

Study information

Study design	Cross-sectional study
Primary study design	Observational
Secondary study design	Cross sectional study
Study setting(s)	University/medical school/dental school
Study type	Diagnostic
Participant information sheet	44980_PIS_consent_V2 09Feb2024.pdf
Scientific title	The association of ectopic fat and cardiovascular disease in people living with HIV and general populations: a cross-sectional analysis
Study hypothesis	A cross-sectional study was designed to assess the relationship between epicardial adipose tissue (EAT) volume and cardiovascular (CVD) risk in people living with HIV (PLWHIV) and general populations. Participants will be recruited from the regional HIV service hosted by Liverpool University Hospitals NHS Foundation Trust (LUHFT). HIV-negative / general population participants will be recruited from those undergoing CT Coronary Angiography.
Ethics approval(s)	Pending submission
Condition	Epicardial adipose tissue (EAT) volume and cardiovascular (CVD) risk in people living with HIV and general populations
Intervention	Pre-screening. Participants will be approached for their interest to be involved in the study from routine clinics. If they are interested then a copy of the patient information leaflet will be provided and contact details passed to the study team. Details will be entered onto the screening log. Participants will be invited to a screening visit (visit 1) where we will take informed written consent upon confirmation of eligibility. Participants will then undergo a brief medical history / focused examination, vital sign check, heart trace, height and weight check. They will then undergo a blood draw for the study bloods (approximately 30mls). In those that consent a subcutaneous fat biopsy will be taken from the gluteal area. All participants will have an ultrasound (FibroScan) of the liver. Participants will then have the MRI visit booked (tolerance 6 weeks from visit 1). Participants will be required to fill in the MRI safety form upon arrival and will undergo a non-contrast MRI (no cannula required). This will take approximately 45-60 minutes. The participant exits the study upon completion of the MRI. Particpants will be contacted at 5 years by a member of the study team to check for cardiovascular events.
Intervention type	Other
Primary outcome measure	Epicardial adipose tissue (mls) measured using cardiac MRI at MRI study visit
Secondary outcome measures	1. Intramyocardial triglyceride concentration (ppm) measured using MR spectroscopy at the MRI study visit 2. Fatty liver (KPa) measured using Fibroscan at screening visit (visit 1) 3. LV ejection fraction (%) measured using cardiac MIR at MRI study visit 4. T1 mapping (ms) measured at cardiac MRI at MRI study visit 5. T2 mapping (ms) measured at cardiac MRI at MRI study visit 6. Left atrial size (mls) measured at cardiac MRI at MRI study visit 7. LV mass (grams) measured at cardiac MRI at MRI study visit 8. Lipid profile (total cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride (mmol/L)) measured at screening visit (visit 1) 9. HBA1c (mmol/mol) measured at screening visit (visit 1) 10. Adiponectin (ug/ml) measured at screening visit (visit 1) 11. Glucose (mmol/L) measured at screening visit (visit 1) 12. Insulin (IU/ml) measured at screening visit (visit 1) 13. HS-CRP (mg/dl) measured at screening visit (visit 1) 14. Leptin (ng/ml) measured at screening visit (visit 1) 15. Follow up 5 year data measured at 5 year telephone follow up
Overall study start date	08/04/2023
Overall study end date	01/03/2025

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	40 Years
Sex	Both
Target number of participants	100
Participant inclusion criteria	1. >40 years old 2. HIV-positive 3. Stable ART for >6 months with two VL <40 copies/ml based on local testing protocols 4. CD4 count >200cells/mm3 for >2 years from recruitment 5. Understand the study procedures, be able to comply with study procedures and voluntarily agree to participate by giving informed written consent
Participant exclusion criteria	1. Subjects unable to comply with the study protocol 2. History of severe renal impairment (eGFR <30ml/min) 3. History of severe hepatic impairment (Child-Pugh Score >9) 4. Active hepatitis B or hepatitis C 5. Any active illness, which in the opinion of the investigator precludes participation in the study 6. History of cancer 7. Active illicit intravenous drug use 8. Investigators may decide the subject cannot proceed if there are any relevant other abnormal results in screening assessments 9. History or current GLP-1 agonist use 10. For female subjects: pregnancy or breastfeeding at screening. 11. Subjects currently taking: Atypical antipsychotics, omega 3 supplements, Telmisartan/Irbesartan, Thiazolidinediones or regular NSAID use 12. Familial hypercholesterolaemia
Recruitment start date	01/03/2024
Recruitment end date	01/02/2025

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Liverpool University Hospitals NHS Foundation Trust

Royal Liverpool University Hospital
Prescot Street
Liverpool
L7 8XP
United Kingdom

Sponsor information

University of Liverpool
University/education

University of Liverpool
Liverpool
L69 3BX
England
United Kingdom

Phone	+44 (0)151 794 2000
Email	sponsor@liverpool.ac.uk
Website	https://www.liverpool.ac.uk/
"ROR"	https://ror.org/04xs57h96

Funders

Funder type

Research organisation

British HIV Association
Private sector organisation / Associations and societies (private and public)

Alternative name(s): BHIVA
Location: United Kingdom

Results and Publications

Intention to publish date	01/09/2025
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
Publication and dissemination plan	Planned publication in high-impact peer-reviewed journals for HIV medicine - HIV Medicine
IPD sharing plan	The data-sharing plans for the current study are unknown and will be made available at a later date

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	version 2	09/02/2024	16/02/2024	No	Yes

Additional files

44980_PIS_consent_V2 09Feb2024.pdf

Editorial Notes

16/02/2024: Trial's existence confirmed by British HIV Association.