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

NCT00179400 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 2000-200
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 2 Diabetes Mellitus

Keywords

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (2)

• Endogenous Glucose Production (EGP)

  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).

  Up to 6 hours

• Glucose Rates of Disappearance (Rd)

  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).

  Up to 6 hours

Secondary Outcomes (4)

• Gene Expression in Both Whole Fat Tissue and Isolated Macrophages

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

• Effects of Pioglitazone on Adipose Tissue Percentage of Macrophage Content

  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 Percentage of Macrophage Content

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

• Adipose Tissue Regulatory T Lymphocyte Content

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

Study Arms (2)

Pioglitazone

ACTIVE COMPARATOR

Participants received Pioglitazone 45 mg via oral capsule daily for 10 or 21 days in randomized, placebo-controlled crossover fashion, separated by a wash-out period. The investigators used a research procedure called a "pancreatic clamp" study to study the effects of the pioglitazone. During the clamp procedure, glucose (a sugar) and insulin (a hormone produced in the pancreas that regulates the amount of glucose in the blood) 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 related to glucose metabolism.

Drug: Pioglitazone; Procedure: Pancreatic Clamp Study

Placebo

PLACEBO COMPARATOR

Participants received matched placebo via oral capsule daily for 10 or 21 days in randomized, placebo-controlled crossover fashion, separated by a wash-out period. The investigators used a research procedure called a "pancreatic clamp" study to study the effects of the pioglitazone. During the clamp procedure, glucose (a sugar) and insulin (a hormone produced in the pancreas that regulates the amount of glucose in the blood) 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 related to glucose metabolism.

Drug: Placebo; Procedure: Pancreatic Clamp Study

Interventions

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.

Also known as: Actos, Thiazolidinedione

Pioglitazone

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.

Also known as: Control

Placebo

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.

Also known as: Glucose clamp technique

Pioglitazone; Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals with Type 2 Diabetes

You may not qualify if:

• 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

Sponsors & Collaborators

• Albert Einstein College of Medicine: lead
• Takeda: collaborator

Study Sites (1)

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Pioglitazone; 2,4-thiazolidinedione; Glucose Clamp Technique

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Chemistry Techniques, Analytical; Investigative Techniques

Results Point of Contact

• Title: Prof. Meredith A. Hawkins
• Organization: Albert Einstein College of Medicine

meredith.hawkins@einsteinmed.edu

718 430 3186

Study Officials

• Meredith Hawkins, M.D., M.S.

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 16, 2005
• Study Start: December 1, 2000
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: March 3, 2025
• Results First Posted: March 3, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)