Trial Outcomes & Findings for Cellular Dynamics of Subcutaneous Fat Distribution in Obese Women (NCT NCT01748994)

Last Updated: 2021-04-30

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

63 participants

Primary outcome timeframe

Change from baseline in adipogenesis at 16 weeks

Results posted on

2021-04-30

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Administration of placebo to upper- and lower-body obese women Placebo	Drug Administration of pioglitazone to upper- and lower-body obese women Pioglitazone: 30mg per day for four months
Overall Study STARTED	31	32
Overall Study COMPLETED	23	26
Overall Study NOT COMPLETED	8	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Administration of placebo to upper- and lower-body obese women Placebo	Drug Administration of pioglitazone to upper- and lower-body obese women Pioglitazone: 30mg per day for four months
Overall Study Lost to Follow-up	8	6

Baseline Characteristics

Cellular Dynamics of Subcutaneous Fat Distribution in Obese Women

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Change from baseline in adipogenesis at 16 weeks

Population: Of the 23 participants in the Placebo group, N=3 did not have adipose tissue biopsy data, and of the 26 participants in the Drug group, N=5 did not have adipose tissue biopsy data. Therefore, the Primary Outcome Analysis only included N=20 and N=21, respectively.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Placebo	Drug n=21 Participants Pioglitazone
In Vivo Adipose Cell Formation (Adipogenesis) Abdominal	-0.3 percent Standard Error 1.5	1.8 percent Standard Error 1.4
In Vivo Adipose Cell Formation (Adipogenesis) Femoral	-1.2 percent Standard Error 1.1	2.1 percent Standard Error 1.1

SECONDARY outcome

Timeframe: Change from baseline in visceral fat at 16 weeks

Population: Of the 23 participants in the Placebo group, N=3 did not have adipose tissue biopsy data, and of the 26 participants in the Drug group, N=5 did not have adipose tissue biopsy data. Therefore, the Secondary Outcome Analysis only included N=20 and N=21, respectively.

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).

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Placebo	Drug n=21 Participants Pioglitazone
Visceral Adipose Tissue (Percentage of Total Abdominal Adipose Tissue)	0.5 percent Standard Error 0.3	-0.8 percent Standard Error 0.3

SECONDARY outcome

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

Population: Of the 23 participants in the Placebo group, N=3 did not have adipose tissue biopsy data, and of the 26 participants in the Drug group, N=5 did not have adipose tissue biopsy data. Therefore, the Secondary Outcome Analysis only included N=20 and N=21, respectively.

Lipid accretion in the liver cells will be measured using 1H-MRS of the liver.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Placebo	Drug n=21 Participants Pioglitazone
Lipid Accretion in the Liver (Intra-hepatic Lipid; IHL)	-0.7 percent Standard Error 1.2	-2.0 percent Standard Error 1.2

SECONDARY outcome

Timeframe: Change from Baseline in Matsuda Index at 16 weeks

Population: Of the 23 participants in the Placebo group, N=3 did not have adipose tissue biopsy data, and of the 26 participants in the Drug group, N=5 did not have adipose tissue biopsy data. Therefore, the Secondary Outcome Analysis only included N=20 and N=21, respectively.

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.

Outcome measures

Outcome measures
Measure	Placebo n=20 Participants Placebo	Drug n=21 Participants Pioglitazone
Matsuda Index (Measure of Insulin Sensitivity)	-0.39 index Standard Error 0.41	0.80 index Standard Error 0.40

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Drug

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo n=31 participants at risk Administration of placebo to upper- and lower-body obese women Placebo	Drug n=32 participants at risk Administration of pioglitazone to upper- and lower-body obese women Pioglitazone: 30mg per day for four months
Nervous system disorders Vertigo (dizziness)	12.9% 4/31	18.8% 6/32
Skin and subcutaneous tissue disorders Skin irritation	19.4% 6/31	18.8% 6/32
Gastrointestinal disorders Gastrointestinal issues	12.9% 4/31	9.4% 3/32
Skin and subcutaneous tissue disorders Skin hematoma	3.2% 1/31	0.00% 0/32

Additional Information

Dr. Eric Ravussin

Pennington Biomedical Research Center

Phone: 225-763-3186

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Placebo n=20 Participants Administration of placebo to upper- and lower-body obese women Placebo	Drug n=21 Participants Administration of pioglitazone to upper- and lower-body obese women Pioglitazone: 30mg per day for four months	Total n=41 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=5 Participants	21 Participants n=7 Participants	41 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	21 Participants n=7 Participants	41 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=5 Participants	21 Participants n=7 Participants	41 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants	21 participants n=7 Participants	41 participants n=5 Participants