Clinical trial NCT01748994: Cellular Dynamics of Subcutaneous Fat Distribution in Obese Women
Official title: Cellular Dynamics of Subcutaneous Fat Distribution in Obese Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Metabolic Syndrome
Keywords: Obesity
Fat distribution
Adipogenesis
Adipocyte
Preadipocyte
Ectopic fat
Lead sponsor: Pennington Biomedical Research Center
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2012-12-13
Enrollment: 63
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The body shape of obese women varies between having the majority of fat either above the waist ("apple" shape) or below the waist ("pear" shape). The study will investigate what restricts: apple"-shaped women from being "pear"-shaped at the cellular level. Since "pear" shaped women tend to have better health, this study will open the door to future research in regulating body shape and thus improving health.

Detailed description: Adipose tissue expandability and the distribution of stored fat in the body are stronger predictors of health risk. A better understanding of the factors that determine regional fat mass growth may lead to developing new strategies for prevention or treatment of metabolic complications of obesity. The objective of this proposal is to study the responsiveness of different fat depots to adipogenic stimulation in upper-body and lower-body obese women.

Eligibility criteria: Inclusion Criteria:

* You are a pre-menopausal woman between 18-40 years of age
* Your Body Mass Index (BMI, weight-to-height2 ratio) is 27 - 38 kg/m2, inclusive
* The ratio of your waist-to-hip circumferences is either \>0.84 ("apple"-type body shape) or \<0.77 ("pear"-type body shape)
* You are willing to undergo a drug intervention for 16 weeks
* You are willing to drink heavy water \[similar to the ordinary water that is highly enriched in the naturally occurring stable (non-radioactive) form of hydrogen, deuterium; also called deuterium-labeled water\] for 8 weeks before the beginning and during the second half of the drug intervention; you will need 24-hours access to a refrigerator for storage of the water.
* You agree to use a double barrier method as a form of birth control to prevent pregnancy. Oral contraceptives (birth control pills) are not allowed in the study. Acceptable methods of birth control are condoms, spermicide, IUD (intrauterine device, must be hormone free - see list in clinic), diaphragm and abstinence. An example of a double barrier method would be condoms plus spermicide, etc.

Exclusion Criteria:

* You have gained or lost more than 4.5 lb (2 kg) in the last 3 months
* You have had significant changes in the diet or level of physical activity within the past month
* You have a blood sugar of greater than 100 or a diagnosis of diabetes.
* You have abnormal liver enzyme values from your blood work
* You have a history of heart, kidney, lung, liver, and thyroid disease
* You have an average blood pressure \>140/90 at your screening visit
* Have you had a positive test for human immunodeficiency virus (HIV), hepatitis B or hepatitis C?
* You require chronic use of medications including diuretics, steroids, thyroid hormones, and adrenergic-stimulating agents (bronchodilators, nasal decongestants)

Primary outcomes:
measure: In Vivo Adipose Cell Formation (Adipogenesis)
timeFrame: Change from baseline in adipogenesis at 16 weeks
Secondary outcomes:
measure: Visceral Adipose Tissue (Percentage of Total Abdominal Adipose Tissue)
timeFrame: Change from baseline in visceral fat at 16 weeks
measure: Lipid Accretion in the Liver (Intra-hepatic Lipid; IHL)
timeFrame: Change from Baseline in intra-hepato-cellular lipid at 16 weeks
measure: Matsuda Index (Measure of Insulin Sensitivity)
timeFrame: Change from Baseline in Matsuda Index at 16 weeks
Other outcomes:
Locations:
city: Baton Rouge
country: United States
facility: Pennington Biomedical Research Center
state: Louisiana
city: Baton Rouge
country: United States
facility: Pennington Biomedical Research Center
state: Louisiana
Study officials:
affiliation: Pennington Biomedical Research Center
name: Eric Ravussin, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: White U, Fitch MD, Beyl RA, Hellerstein MK, Ravussin E. Adipose depot-specific effects of 16 weeks of pioglitazone on in vivo adipogenesis in women with obesity: a randomised controlled trial. Diabetologia. 2021 Jan;64(1):159-167. doi: 10.1007/s00125-020-05281-7. Epub 2020 Oct 1.
citation: White UA, Fitch MD, Beyl RA, Hellerstein MK, Ravussin E. Racial differences in in vivo adipose lipid kinetics in humans. J Lipid Res. 2018 Sep;59(9):1738-1744. doi: 10.1194/jlr.P082628. Epub 2018 Jun 17.
citation: White UA, Fitch MD, Beyl RA, Hellerstein MK, Ravussin E. Differences in In Vivo Cellular Kinetics in Abdominal and Femoral Subcutaneous Adipose Tissue in Women. Diabetes. 2016 Jun;65(6):1642-7. doi: 10.2337/db15-1617. Epub 2016 Mar 18.