Clinical trial NCT05383456: The Visceral Adiposity Measurement and Observation Study
Official title: The Visceral Adiposity Measurement and Observation Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV
HIV-Infections
HIV-1-infection
HIV I Infection
HIV Lipodystrophy
HIV Infection Primary
HIV-Associated Lipodystrophy
HIV Disease Progression
Lipohypertrophy
Liver Diseases
NAFLD
NASH
Liver Fibrosis
Hepatic Fibrosis
Waist Circumference
BMI
Ectopic Fat
Liver Fat
Hepatic Steatosis
Keywords: HIV
HIV Infections
HIV-1-infection
HIV Lipodystrophy
HIV Infection Primary
HIV-Associated Lipodystrophy
HIV Disease Progression
Lipohypertrophy
Liver Disease
NAFLD, Liver Fat, Hepatic Steatosis
NASH
Liver Fibrosis and Hepatic Fibrosis
Ectopic Fat
Pericardial Fat
Muscle Fat/Density
Liver CAP
Liver VTCE
Waist Circumference
Anthropometric Measurements
BMI
Hip Circumference
Waist to Hip Ratio
Lead sponsor: Theratechnologies
Sponsor class: INDUSTRY
Collaborators: name: Dacima Consulting
name: Medpace, Inc.
name: Vanderbilt University Medical Center
name: Echosens
First posted: 2022-05-20
Enrollment: 196
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The overall study population will include all participants who provide informed consent, are enrolled in the study, and complete all study procedures as required.

The cardiovascular risk analysis population will not include participants who have history of CVD (myocardial infarction, cerebrovascular accident, heart failure, or atrial fibrillation).

Diagnosis of normal versus excess VA using published criteria12,15,16,20 (normal visceral adiposity (NVA) versus EVA) will be based on CT evidence of VA cross-sectional area (\<130cm2 or ≥130cm2, respectively).

Brief summary: The Visceral Adiposity Measurement and Observation Study

Detailed description: Visceral adiposity (VA) is a form of ectopic fat deposition that correlates with cardiometabolic risk in both the general population and among people with human immunodeficiency virus (HIV) (PWH).1 Excess VA (EVA) is prevalent among PWH,2,3 and prevalence rises with age and time on antiretroviral treatment.3 Effective plasma virologic suppression is not protective against EVA and associated comorbidities, possibly due to adverse metabolic effects of certain antiretroviral agents, the low-level expression of HIV gene products within the adipose tissue, and other factos.4

Although EVA has been reported to occur in nearly half of PWH on antiretroviral therapy (ART),2,3 it may go unrecognized or be mischaracterized as generalized obesity. Whereas obesity and EVA both increase waist circumference (WC), they differ in that overweight and obese individuals accumulate fat primarily in subcutaneous depots, whereas individuals with EVA accumulate fat within the abdominal cavity. Ectopic fat accumulation (EFA) also occurs at various other depots, namely around and within various internal organs (e.g., the heart, skeletal muscle, liver, and pancreas).1,5 For purposes of the VAMOS study, EFA is defined as the amount of pericardial fat, skeletal muscle fat, and liver fat the VAMOS study subjects have. VA for the VAMOS study is held separately as it is the primary endpoint.

Because it represents a potentially modifiable cardiovascular risk factor among PWH, simple, practical surrogate markers are needed to identify patients with probable EVA. Anthropometric measurements such as WC correlate with EVA in the general population1, but their predictive value is less well defined for subgroups of PWH.

Eligibility criteria: Inclusion Criteria:

1. Adult, ≥18 years
2. HIV+, on continuous ART for ≥12 months
3. ≥3 years since initiation of ART
4. 20.0 ≤ BMI ≤ 40.0 kg/m2

Exclusion Criteria:

1. Detectable HIV plasma viremia 12 months prior enrollment, defined by ≥1 measurement of HIV-1 ribonucleic acid (RNA) \> 1000/mL
2. Unable or unwilling to undergo any study procedures
3. Known hepatic cirrhosis
4. Active hepatitis C within past 12 months, defined by detectable hepatitis C RNA
5. Hepatitis B positive
6. Current pregnancy or breastfeeding
7. History of liver transplant
8. Self-reported weekly alcohol consumption meets National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria for problematic drinking (binge or chronic daily intake)
9. Any active malignancy, excluding non-melanoma skin cancer
10. Patient has been treated with tesamorelin or human growth hormone within the last 12 months
11. Patient has used insulin in the previous year
12. Patient has undergone bariatric surgery in the year prior to enrollment or is currently undergoing a weight loss program

Primary outcomes:
measure: Umbilical waist circumference measurement (in cm).
timeFrame: Baseline
measure: Iliac waist circumference measurement (in cm).
timeFrame: Baseline
measure: Visceral Adiposity Measurement by CT surface area (cm2).
timeFrame: Baseline
Secondary outcomes:
measure: Visceral Adiposity Measurement by CT surface area (cm2)
timeFrame: Baseline
measure: Visceral Adiposity Measurement by CT volume (cm3).
timeFrame: Baseline
measure: Weight in kg and height in meter will be combined to report body mass index (BMI) in kg/m2.
timeFrame: Baseline
measure: Health related quality of life evaluation by SF-36 questionnaire
timeFrame: Baseline
measure: Health related quality of life evaluation by VAMOS disease specific questionnaire
timeFrame: Baseline
measure: Framingham Cardiovascular Risk strata (low, intermediate or high)
timeFrame: Baseline
measure: Fibroscan Controlled Attenuation Parameter (CAP) in decibels/minute
timeFrame: Baseline
measure: Fibroscan Vibration Controlled Transient Elastography (VCTE) in kPa
timeFrame: Baseline
measure: Glucose homeostasis as measured by percentage (%) of glycated form of hemoglobin in blood (HbA1c).
timeFrame: Baseline
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Ruane Clinical Research
state: California
city: Fort Lauderdale
country: United States
facility: AIDS Healthcare Foundation
state: Florida
city: Miami Beach
country: United States
facility: AIDS Healthcare Foundation
state: Florida
city: Miami Beach
country: United States
facility: AIDS Healthcare Foundation
state: Florida
city: Orlando
country: United States
facility: Bliss Health
state: Florida
city: New York
country: United States
facility: AIDS Healthcare Foundation
state: New York
city: Philadelphia
country: United States
facility: Fight Community Health Centers
state: Pennsylvania
city: Dallas
country: United States
facility: Prism Health North Texas
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Jordan Lake, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University Medical Center
name: John Koethe, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University Medical Center
name: Jeffery Carr, DR
role: PRINCIPAL_INVESTIGATOR
References:
citation: Neeland IJ, Ross R, Despres JP, Matsuzawa Y, Yamashita S, Shai I, Seidell J, Magni P, Santos RD, Arsenault B, Cuevas A, Hu FB, Griffin B, Zambon A, Barter P, Fruchart JC, Eckel RH; International Atherosclerosis Society; International Chair on Cardiometabolic Risk Working Group on Visceral Obesity. Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: a position statement. Lancet Diabetes Endocrinol. 2019 Sep;7(9):715-725. doi: 10.1016/S2213-8587(19)30084-1. Epub 2019 Jul 10.
citation: Guilbaud L, Guedes JC, Gomez B, Gagne C, Thomas R, Szabo J. Lipohypertrophy, a preliminary estimate in the prevalence in an urban Canadian HIV clinic. Presented at the May 2019 CAHR Conference, Saskatoon SK. Poster 4420.
citation: Alikhani A, Morin H, Matte S, Alikhani P, Tremblay C, Durand M. Association between lipodystrophy and length of exposure to ARTs in adult HIV-1 infected patients in Montreal. BMC Infect Dis. 2019 Sep 18;19(1):820. doi: 10.1186/s12879-019-4446-9.
citation: Koethe JR. Adipose Tissue in HIV Infection. Compr Physiol. 2017 Sep 12;7(4):1339-1357. doi: 10.1002/cphy.c160028.
citation: Orlando G, Guaraldi G, Zona S, Carli F, Bagni P, Menozzi M, Cocchi S, Scaglioni R, Ligabue G, Raggi P. Ectopic fat is linked to prior cardiovascular events in men with HIV. J Acquir Immune Defic Syndr. 2012 Apr 15;59(5):494-7. doi: 10.1097/QAI.0b013e31824c8397.
citation: Fourman LT, Kileel EM, Hubbard J, Holmes T, Anderson EJ, Looby SE, Fitch KV, Feldpausch MN, Torriani M, Lo J, Stanley TL, Grinspoon SK. Comparison of visceral fat measurement by dual-energy X-ray absorptiometry to computed tomography in HIV and non-HIV. Nutr Diabetes. 2019 Feb 25;9(1):6. doi: 10.1038/s41387-019-0073-1.
citation: Lemoine M, Assoumou L, De Wit S, Girard PM, Valantin MA, Katlama C, Necsoi C, Campa P, Huefner AD, Schulze Zur Wiesch J, Rougier H, Bastard JP, Stocker H, Mauss S, Serfaty L, Ratziu V, Menu Y, Schlue J, Behrens G, Bedossa P, Capeau J, Ingiliz P, Costagliola D; ANRS-ECHAM Group. Diagnostic Accuracy of Noninvasive Markers of Steatosis, NASH, and Liver Fibrosis in HIV-Monoinfected Individuals at Risk of Nonalcoholic Fatty Liver Disease (NAFLD): Results From the ECHAM Study. J Acquir Immune Defic Syndr. 2019 Apr 1;80(4):e86-e94. doi: 10.1097/QAI.0000000000001936.
citation: Lake JE, Stanley TL, Apovian CM, Bhasin S, Brown TT, Capeau J, Currier JS, Dube MP, Falutz J, Grinspoon SK, Guaraldi G, Martinez E, McComsey GA, Sattler FR, Erlandson KM. Practical Review of Recognition and Management of Obesity and Lipohypertrophy in Human Immunodeficiency Virus Infection. Clin Infect Dis. 2017 May 15;64(10):1422-1429. doi: 10.1093/cid/cix178.
citation: Gabriel CL, Ye F, Fan R, Nair S, Terry JG, Carr JJ, Silver H, Baker P, Hannah L, Wanjalla C, Mashayekhi M, Bailin S, Lima M, Woodward B, Izzy M, Ferguson JF, Koethe JR. Hepatic Steatosis and Ectopic Fat Are Associated With Differences in Subcutaneous Adipose Tissue Gene Expression in People With HIV. Hepatol Commun. 2021 Feb 27;5(7):1224-1237. doi: 10.1002/hep4.1695. eCollection 2021 Jul.
citation: Monczor AN, Li X, Palella FJ Jr, Erlandson KM, Wiley D, Kingsley LA, Post WS, Jacobson LP, Brown TT, Lake JE. Systemic Inflammation Characterizes Lack of Metabolic Health in Nonobese HIV-Infected Men. Mediators Inflamm. 2018 Sep 25;2018:5327361. doi: 10.1155/2018/5327361. eCollection 2018.
citation: Beraldo RA, Meliscki GC, Silva BR, Navarro AM, Bollela VR, Schmidt A, Foss-Freitas MC. Comparing the Ability of Anthropometric Indicators in Identifying Metabolic Syndrome in HIV Patients. PLoS One. 2016 Feb 26;11(2):e0149905. doi: 10.1371/journal.pone.0149905. eCollection 2016.
citation: Koethe JR, Lagathu C, Lake JE, Domingo P, Calmy A, Falutz J, Brown TT, Capeau J. HIV and antiretroviral therapy-related fat alterations. Nat Rev Dis Primers. 2020 Jun 18;6(1):48. doi: 10.1038/s41572-020-0181-1.
citation: Pouliot MC, Despres JP, Lemieux S, Moorjani S, Bouchard C, Tremblay A, Nadeau A, Lupien PJ. Waist circumference and abdominal sagittal diameter: best simple anthropometric indexes of abdominal visceral adipose tissue accumulation and related cardiovascular risk in men and women. Am J Cardiol. 1994 Mar 1;73(7):460-8. doi: 10.1016/0002-9149(94)90676-9.
citation: O'Neill T, Guaraldi G, Orlando G, Carli F, Garlassi E, Zona S, Despres JP, Ross R. Combined use of waist and hip circumference to identify abdominally obese HIV-infected patients at increased health risk. PLoS One. 2013 May 20;8(5):e62538. doi: 10.1371/journal.pone.0062538. Print 2013.
citation: Hunter GR, Snyder SW, Kekes-Szabo T, Nicholson C, Berland L. Intra-abdominal adipose tissue values associated with risk of possessing elevated blood lipids and blood pressure. Obes Res. 1994 Nov;2(6):563-8. doi: 10.1002/j.1550-8528.1994.tb00106.x.
citation: Yoo S, Sung MW, Kim H. CT-defined visceral adipose tissue thresholds for identifying metabolic complications: a cross-sectional study in the United Arab Emirates. BMJ Open. 2020 Aug 11;10(8):e031181. doi: 10.1136/bmjopen-2019-031181.
citation: Katzmarzyk PT, Greenway FL, Heymsfield SB, Bouchard C. Clinical utility and reproducibility of visceral adipose tissue measurements derived from dual-energy X-ray absorptiometry in White and African American adults. Obesity (Silver Spring). 2013 Nov;21(11):2221-4. doi: 10.1002/oby.20519. Epub 2013 Aug 13.
citation: Williams MJ, Hunter GR, Kekes-Szabo T, Trueth MS, Snyder S, Berland L, Blaudeau T. Intra-abdominal adipose tissue cut-points related to elevated cardiovascular risk in women. Int J Obes Relat Metab Disord. 1996 Jul;20(7):613-7.
citation: Katzmarzyk PT, Heymsfield SB, Bouchard C. Clinical utility of visceral adipose tissue for the identification of cardiometabolic risk in white and African American adults. Am J Clin Nutr. 2013 Mar;97(3):480-6. doi: 10.3945/ajcn.112.047787. Epub 2013 Jan 30.
citation: Lemieux S, Prud'homme D, Bouchard C, Tremblay A, Despres JP. A single threshold value of waist girth identifies normal-weight and overweight subjects with excess visceral adipose tissue. Am J Clin Nutr. 1996 Nov;64(5):685-93. doi: 10.1093/ajcn/64.5.685.
citation: Rankinen T, Kim SY, Perusse L, Despres JP, Bouchard C. The prediction of abdominal visceral fat level from body composition and anthropometry: ROC analysis. Int J Obes Relat Metab Disord. 1999 Aug;23(8):801-9. doi: 10.1038/sj.ijo.0800929.
citation: Falutz J, Rosenthall L, Kotler D, Zona S, Guaraldi G. Surrogate markers of visceral adipose tissue in treated HIV-infected patients: accuracy of waist circumference determination. HIV Med. 2014 Feb;15(2):98-107. doi: 10.1111/hiv.12085. Epub 2013 Sep 22.
citation: Zhou Q, Usadel S, Kern W, Zirlik A, Mueller MC. Real world cardiovascular risk assessment using reduced DAD, SCORE and Framingham equations in a German HIV cohort. Eur Heart J. 2020;41 (Suppl. 2):ehaa946.2914.
citation: Beraldo RA, Meliscki GC, Silva BR, Navarro AM, Bollela VR, Schmidt A, Foss-Freitas MC. Anthropometric measures of central adiposity are highly concordant with predictors of cardiovascular disease risk in HIV patients. Am J Clin Nutr. 2018 Jun 1;107(6):883-893. doi: 10.1093/ajcn/nqy049.