Insulin Signaling in Skeletal Muscle

Effect of Metformin and Pioglitazone on Insulin Signaling in Skeletal Muscle

The insulin sensitizing effects of metformin and pioglitazone in the skeletal muscle remain unknown. Our group aims to analyze molecular changes within the skeletal muscle of pre-diabetic patients through the use of a clinical trial in humans.

Study Overview

• Status: Withdrawn
• Conditions: Insulin Sensitivity
• Intervention / Treatment: Drug: Placebo; Drug: Metformin; Drug: Pioglitazone

• Study Type: Interventional
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pre-diabetes as defined by an oral glucose tolerance test 2-hour level between 140 and 200 mg/dL

General Inclusion Criteria:

• Able to communicate meaningfully with the investigator and legally competent to provide informed written consent.
• Female subjects must be non-lactating, have a negative pregnancy test, and be on acceptable birth control.

Exclusion Criteria:

• Oral glucose tolerance test <140 or >200mg/dL

• Treated with any of the following medications:

  • Systemic glucocorticoids (more than 2 weeks), antineoplastic agents, transplant medications, fibrates, anti-retroviral medications, or thiazolidinediones within 6 months prior to screening
  • Start or change of hormonal replacement therapy within 3 months prior to screening
  • Short-acting insulin (more than15 units per day) in DMT2 subjects, indicating severe insulin deficiency within 6 months prior to screening

• History or presence of any of the following conditions:

  • Clinically significant heart disease (New York Heart Classification greater than grade II; more than non-specific ST-T wave changes on the EKG)
  • Peripheral vascular disease (history of claudication)
  • Clinically significant pulmonary disease.
  • Current uncontrolled hypertension (systolic BP>160 mmHg, diastolic BP>100 mmHg)
  • History or presence of malignancy other than basal cell or squamous cell skin cancer
  • Autonomic neuropathy
  • Clinically significant hematologic disease

• Any of the following abnormal laboratory values:

  • Hematocrit < 35 vol%
  • Serum creatinine > 1.6 mg/dl
  • AST, ALT or Alkaline phosphatase > 2.5 times the upper limit of normal
  • PT, PTT outside the normal reference range
  • TSH outside the normal reference range
  • Triglycerides > 400 mg/dl
  • Platelet count < 50,000
• Current or history of drug abuse or alcohol abuse
• Blood donation within 2 months prior to screening
• Engage in exercise with moderate to hard intensity for greater than 1 hour per day for 5 or more days per week.
• Diagnosed with Type 1 diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; oral, once daily
Experimental: Metformin	Drug: Metformin; oral, 850 mg twice daily
Experimental: Pioglitazone	Drug: Pioglitazone; oral, 45 mg daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proteomic	Changes in global protein abundance levels	3 months
Proteomic 2	Changes in global protein phosphorylation levels	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Epigenomic	Change in global DNA percent methylation	3 months

Collaborators and Investigators

• Sponsor: Wayne State University

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2019
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): June 1, 2025

Study Registration Dates

• First Submitted: February 12, 2018
• First Submitted That Met QC Criteria: February 28, 2018
• First Posted (Actual): March 2, 2018

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 5, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin; Pioglitazone
• Other Study ID Numbers: MetPioMuscle

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes