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Cellular Dynamics of Subcutaneous Fat Distribution in Obese Women (Apple/Pear)

Primary Purpose

Obesity, Metabolic Syndrome

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Pioglitazone
Placebo
Sponsored by
Pennington Biomedical Research Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Obesity focused on measuring Obesity, Fat distribution, Adipogenesis, Adipocyte, Preadipocyte, Ectopic fat

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleAccepts Healthy Volunteers

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)

Sites / Locations

  • Pennington Biomedical Research Center
  • Pennington Biomedical Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

Drug

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Visceral Adipose Tissue (Percentage of Total Abdominal Adipose Tissue)
The volume of fat tissue around the internal organs in the abdomen (visceral adipose tissue; VAT) and underneath the skin (subcutaneous abdominal adipose tissue; scABD) will be determined by Magnetic Resonance Imaging (MRI) of the abdominal region. VAT:total abdominal AT (TAT) reflects the percentage of abdominal fat that is VAT and is calculated as VAT/(scABD AT + VAT).
Lipid Accretion in the Liver (Intra-hepatic Lipid; IHL)
Lipid accretion in the liver cells will be measured using 1H-MRS of the liver.
Matsuda Index (Measure of Insulin Sensitivity)
Insulin sensitivity (glucose tolerance) will be assessed using an oral 75 g oral glucose tolerance test (OGTT) after an overnight fast. Blood samples will be collected at 0, 30, 60, 90, and 120 min after glucose administration to measure serum glucose and insulin. Insulin sensitivity was calculated using the Matsuda insulin sensitivity index [10,000/ √(glucose 0' x insulin 0') X (mean glucose OGTT x mean insulin OGTT)]. A higher value denotes increased insulin sensitivity.

Full Information

First Posted
December 10, 2012
Last Updated
April 29, 2021
Sponsor
Pennington Biomedical Research Center
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT01748994
Brief Title
Cellular Dynamics of Subcutaneous Fat Distribution in Obese Women
Acronym
Apple/Pear
Official Title
Cellular Dynamics of Subcutaneous Fat Distribution in Obese Women
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
February 2011 (undefined)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Pennington Biomedical Research Center
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Metabolic Syndrome
Keywords
Obesity, Fat distribution, Adipogenesis, Adipocyte, Preadipocyte, Ectopic fat

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
63 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Administration of placebo to upper- and lower-body obese women
Arm Title
Drug
Arm Type
Active Comparator
Arm Description
Administration of pioglitazone to upper- and lower-body obese women
Intervention Type
Drug
Intervention Name(s)
Pioglitazone
Other Intervention Name(s)
Actos
Intervention Description
30mg per day for four months
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
In Vivo Adipose Cell Formation (Adipogenesis)
Description
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.
Time Frame
Change from baseline in adipogenesis at 16 weeks
Secondary Outcome Measure Information:
Title
Visceral Adipose Tissue (Percentage of Total Abdominal Adipose Tissue)
Description
The volume of fat tissue around the internal organs in the abdomen (visceral adipose tissue; VAT) and underneath the skin (subcutaneous abdominal adipose tissue; scABD) will be determined by Magnetic Resonance Imaging (MRI) of the abdominal region. VAT:total abdominal AT (TAT) reflects the percentage of abdominal fat that is VAT and is calculated as VAT/(scABD AT + VAT).
Time Frame
Change from baseline in visceral fat at 16 weeks
Title
Lipid Accretion in the Liver (Intra-hepatic Lipid; IHL)
Description
Lipid accretion in the liver cells will be measured using 1H-MRS of the liver.
Time Frame
Change from Baseline in intra-hepato-cellular lipid at 16 weeks
Title
Matsuda Index (Measure of Insulin Sensitivity)
Description
Insulin sensitivity (glucose tolerance) will be assessed using an oral 75 g oral glucose tolerance test (OGTT) after an overnight fast. Blood samples will be collected at 0, 30, 60, 90, and 120 min after glucose administration to measure serum glucose and insulin. Insulin sensitivity was calculated using the Matsuda insulin sensitivity index [10,000/ √(glucose 0' x insulin 0') X (mean glucose OGTT x mean insulin OGTT)]. A higher value denotes increased insulin sensitivity.
Time Frame
Change from Baseline in Matsuda Index at 16 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric Ravussin, PhD
Organizational Affiliation
Pennington Biomedical Research Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Pennington Biomedical Research Center
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70808
Country
United States
Facility Name
Pennington Biomedical Research Center
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70809
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
33001232
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.
Results Reference
derived
PubMed Identifier
29910190
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.
Results Reference
derived
PubMed Identifier
26993068
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.
Results Reference
derived

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Cellular Dynamics of Subcutaneous Fat Distribution in Obese Women

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