Effects of Pioglitazone on Insulin Sensitivity in Healthy Overweight and Obese Males (MK-0000-170)

A Randomized Clinical Trial to Measure the Effect of Pioglitazone on Insulin Sensitivity in Healthy Overweight and Obese Males

The purpose of this study is to evaluate whether 30 mg of pioglitazone administered once daily for up to 28 days to healthy overweight and obese subjects will lead to a significant change in insulin sensitivity, measured in the setting of a hyperinsulinemic euglycemic clamp

Study Overview

• Status: Completed
• Conditions: Healthy; Obesity; Overweight
• Intervention / Treatment: Drug: Comparator: Pioglitazone; Drug: Comparator: Hyperinsulinemic Euglycemic Clamp; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Subject has a BMI of greater than 28 kg/m^2 and less than or equal to 38 kg/m^2
• Subject has been a nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 6 months
• Subject is willing to avoid major dietary changes for the duration of the study

Exclusion Criteria:

• Subject has history of diabetes (Type 1, Type 2 or steroid-induced)
• Subject has a history of hypersensitivity to pioglitazone or other thiazolidinediones
• Subject has a history of liver disease, other than non-alcoholic fatty liver disease or non-alcoholic steatohepatitis
• Subject has a history of congestive heart failure
• Subject has a active or past history of atherosclerotic heart disease, heart failure, osteoporosis, osteopenia, recurrent bone fractures, or anemia
• Subject has a history of stroke, chronic seizures, or major neurological disorder
• Subject has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological or renal abnormalities or diseases
• Subject has a history of neoplastic disease within the past 5 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Comparator: Hyperinsulinemic Euglycemic Clamp; Infusion of Glucose (20% dextrose) to achieve a glucose concentration of 90mg/dL; Infusion of Insulin at a rate of 10 mU/m2/minute from 0 to 180 minutes and at a rate of 40 mU/m2/minute from 180 to 360 minutes; Saline infusion at 60 minutes before the insulin and glucose infusions to keep the antecubital vein open.; Drug: Placebo; Placebo (to match pioglitazone 30 mg) once daily
Active Comparator: Pioglitazone 30 mg	Drug: Comparator: Pioglitazone; Pioglitazone 30 mg once daily; Drug: Comparator: Hyperinsulinemic Euglycemic Clamp; Infusion of Glucose (20% dextrose) to achieve a glucose concentration of 90mg/dL; Infusion of Insulin at a rate of 10 mU/m2/minute from 0 to 180 minutes and at a rate of 40 mU/m2/minute from 180 to 360 minutes; Saline infusion at 60 minutes before the insulin and glucose infusions to keep the antecubital vein open.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in glucose infusion rate (M) during the high dose portion of the hyperinsulinemic euglycemic clamp after 28 days of dosing.	Baseline and 28 days
Change from baseline in glucose infusion rate (M) during the high dose portion of the hyperinsulinemic euglycemic clamp after 14 days of dosing	Baseline and 14 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in glucose infusion rate (M) during the low dose portion of the hyperinsulinemic euglycemic clamp after 28 days of dosing.	Baseline and 28 days
Change from baseline in glucose infusion rate (M) during the low dose portion of the hyperinsulinemic euglycemic clamp after 14 days of dosing	Baseline and 14 days

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Shankar SS, Shankar RR, Railkar RA, Beals CR, Steinberg HO, Kelley DE. Early Clinical Detection of Pharmacologic Response in Insulin Action in a Nondiabetic Insulin-Resistant Population. Curr Ther Res Clin Exp. 2015 Aug 14;77:83-9. doi: 10.1016/j.curtheres.2015.08.001. eCollection 2015 Dec.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: April 30, 2010
• First Submitted That Met QC Criteria: May 3, 2010
• First Posted (Estimate): May 4, 2010

Study Record Updates

• Last Update Posted (Estimate): October 2, 2015
• Last Update Submitted That Met QC Criteria: October 1, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Healthy Volunteers
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Body Weight; Hyperinsulinism; Insulin Resistance; Overweight; Hypoglycemic Agents; Physiological Effects of Drugs; Pioglitazone
• Other Study ID Numbers: 0000-170; 170 (Other Identifier: Merck)