Cellular Dynamics of Subcutaneous Fat Distribution in Obese Women

NCT01748994 | Completed Results DMC

• 2 other identifiers: PBRC 100395R01DK090607
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 2

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.

Conditions

Obesity; Metabolic Syndrome

Keywords

Obesity; Fat distribution; Adipogenesis; Adipocyte; Preadipocyte; Ectopic fat

Outcome Measures

Primary Outcomes (1)

• In Vivo Adipose Cell Formation (Adipogenesis)

  Following the consumption of water labeled with the stable isotope deuterium (2H2O; heavy water), adipose tissue biopsies from the subcutaneous abdominal and femoral (thigh) depots will be collected. The 2H from the heavy water is enriched into the DNA of newly synthesized cells. Measures of DNA synthesis (obtained via gas chromatography and mass spectrometry analysis of 2H-enrichment) denote new adipose cell formation, or adipogenesis. The primary outcome is to assess the change (from baseline) in adipose cell formation rates (i.e. adipogenesis) in response to 16-weeks of pioglitazone versus the control group.

  Change from baseline in adipogenesis at 16 weeks

Secondary Outcomes (3)

• Visceral Adipose Tissue (Percentage of Total Abdominal Adipose Tissue)

  Change from baseline in visceral fat at 16 weeks

• Lipid Accretion in the Liver (Intra-hepatic Lipid; IHL)

  Change from Baseline in intra-hepato-cellular lipid at 16 weeks

• Matsuda Index (Measure of Insulin Sensitivity)

  Change from Baseline in Matsuda Index at 16 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Administration of placebo to upper- and lower-body obese women

Drug: Placebo

Drug

ACTIVE COMPARATOR

Administration of pioglitazone to upper- and lower-body obese women

Drug: Pioglitazone

Interventions

Pioglitazone DRUG

30mg per day for four months

Also known as: Actos

Drug

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Pennington Biomedical Research Center: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (2)

Pennington Biomedical Research Center

Baton Rouge, Louisiana, 70808, United States

Location

Pennington Biomedical Research Center

Baton Rouge, Louisiana, 70809, United States

Location

Related Publications (3)

• 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.

  PMID: 33001232 DERIVED

• 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.

  PMID: 29910190 DERIVED

• 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.

  PMID: 26993068 DERIVED

MeSH Terms

Conditions

Obesity; Metabolic Syndrome

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Eric Ravussin
• Organization: Pennington Biomedical Research Center

eric.ravussin@pbrc.edu

225-763-3186

Study Officials

• Eric Ravussin, PhD

  Pennington Biomedical Research Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 10, 2012
• First Posted: December 13, 2012
• Study Start: February 1, 2011
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: April 30, 2021
• Results First Posted: April 30, 2021

Record last verified: 2021-04

Locations

US (2)