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Completed

NCT Number: NCT00179400

The Role of Acute Combined PPAR Alpha and Gamma Stimulation on Insulin Action in Humans

The purpose of this study is to investigate the acute effects of the thiazolidinedione agent pioglitazone (which has combined PPAR alpha and gamma stimulation) on insulin's ability to suppress glucose production, stimulated glucose uptake, and impact a number of other metabolically important endpoints, including production of adiponectin (a protein hormone which regulates sugar levels and fatty acid breakdown) in subjects with type 2 diabetes.

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Key information

Conditions

Type 2 Diabetes Mellitus Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

About this study

Participants in this study were given a supply of either pioglitazone (a medication used to treat diabetes) or matched placebo for a duration of 10 days or 21 days. Changes to the body's response to insulin in the liver and in peripheral tissues (eg, muscle and fat) will be measured using a procedure called a pancreatic clamp. During the clamp procedure, glucose (a sugar) and insulin were infused with an intravenous catheter, and blood samples were collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are found in the body and are related to glucose metabolism. Small amounts of muscle and fat tissue were also taken during this study to measure changes in gene expression after taking the medication/placebo.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Individuals with Type 2 Diabetes

Exclusion criteria

  • Individuals with bleeding disorders including gastrointestinal reflux disease (GERD), peptic ulcer disease (PUD), any gastrointestinal (GI) bleeding
  • High blood pressure
  • History of Coronary Artery Disease or chest pain on exertion

Treatment and study plan

pioglitazone

Drug

This was a randomized placebo-controlled crossover study in which subjects received both agents in random order, separated by a wash-out period. Following 10 or 21 days' intervention, subjects underwent a pancreatic clamp study.

Other names: Actos, Thiazolidinedione

Placebo

Drug

This was a randomized placebo-controlled crossover study in which subjects received both agents in random order, separated by a wash-out period. Following 10 or 21 days' intervention, subjects underwent a pancreatic clamp study.

Other names: Control

Pancreatic Clamp Study

Procedure

During the clamp procedure, glucose (a sugar) and insulin were infused with an IV catheter, and blood samples were collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are found in the body and are related to glucose metabolism.

Other names: Glucose clamp technique

Primary outcomes

  1. Endogenous Glucose Production (EGP)

    Time frame: Up to 6 hours

    EGP (a measure of the body's production of sugar) was measured by using a 6-hour stepped pancreatic clamp procedure under various treatment conditions (e.g., Pioglitazone or placebo at 10-days and/or 21-days), by monitoring the level of a non-radioactive, naturally occurring form of glucose (sugar). The relevant data at the end of each last 60 minute bin of each run was reported for each of the four groups up to 6 hours. Results are summarized by study arm/group and reported in milligrams/kilograms/minute (mg/kg/min).

  2. Glucose Rates of Disappearance (Rd)

    Time frame: Up to 6 hours

    Glucose rates of disappearance were measured using a stepped pancreatic clamp study procedure under various treatment conditions (e.g., Pioglitazone or placebo at 10-days and/or 21-days) by monitoring the level of a non-radioactive, naturally occurring form of glucose (sugar). For purposes of this study, the most relevant data for the final hour is summarized within each study Pioglitazone and Placebo study arm/group, respectively. Results are summarized by study arm/group and reported in milligrams/kilograms/minute (mg/kg/min).

Secondary outcomes

  1. Gene Expression in Both Whole Fat Tissue and Isolated Macrophages

    Time frame: Outcome was compared prior to and post 10-day or 21-day administration of either placebo or Pioglitazone

    Gene expression of inflammatory markers in both whole fat tissue and isolated macrophages were studied by quantitative, real-time reverse transcriptase polymerase chain reaction (RT-PCR) in placebo and Pioglitazone groups of either 10- or 21-day study. The reporting data was calculated as the ratio between the target genes and housekeeping genes in either the 10- or 21-day study.

  2. Effects of Pioglitazone on Adipose Tissue Percentage of Macrophage Content

    Time frame: Assessed at day 1 prior to the intervention and on day 10 or 21 following the intervention, day 10 or 21 following the intervention reported

    Adipose tissue biopsy was performed on day one or on the last day (10th or 21st day) for the corresponding Pioglitazone and placebo interventions. Macrophages were stained with immunofluorescence antibody after isolation from adipose tissue and processed. The percentage of macrophage content in stromal vascular fraction cells (SVF) analyzed by Fluorescence-activated cell sorter analysis (FACS) was determined. Results are summarized by study arm/group and reported in milligrams/kilograms/minute (mg/kg/min).

  3. Adipose Tissue Percentage of Macrophage Content

    Time frame: Outcome was compared between Pioglitazone and placebo group prior to and after 21-day administration

    Adipose tissue percentage of macrophage content was analyzed by Immuno-fluorescence staining (iNOS+ and CD68+). Both the immuno-fluorescence stained macrophages and all other stained cells will be counted after staining. The percentage of macrophage content will be calculated as the the ratio between the number of macrophage and all other cells.

  4. Adipose Tissue Regulatory T Lymphocyte Content

    Time frame: Outcome was compared between Pioglitazone and placebo group prior to and after 21-day administration

    Adipose tissue T lymphocyte content (%) was analyzed by Immunohistochemistry (IHC) staining with Treg-specific marker FOXP3

    Both the IHC FOXP3 stained T lymphocyte and all other stained cells will be counted after staining. The percentage of T lymphocyte content will be calculated as the the ratio between the number of T lymphocyte and all other cells.

Sponsors and collaborators

Lead sponsor

Albert Einstein College of Medicine

Other

Collaborators

  • Takeda

Registry information

Official study title

The Role of Acute Combined Peroxisome Proliferator-Activated Receptors (PPAR) Alpha and Gamma Stimulation on Insulin Action in Humans

Important dates

Study start
2000
Primary completion
2011
Study completion
2011
First posted
Sep 16, 2005
Registry last updated
Mar 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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