Insulin Signaling in Skeletal Muscle

Phase 2

Withdrawn

• Conditions: Insulin Sensitivity
• Interventions: Drug: Placebo; Drug: Pioglitazone; Drug: Metformin

• Registration Number: NCT03452267
• Lead Sponsor: Wayne State University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-02-12
• Study First Submitted QC: 2018-02-28
• Study First Posted: 2018-03-02
• Study Start: 2019-09-01
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-05
• Last Update Posted: 2020-10-08
• Primary Completion: 2024-12
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Pioglitazone	Pioglitazone	-
Metformin	Metformin	-

Primary Outcome Measures

Name	Time	Method
Proteomic	3 months	Changes in global protein abundance levels
Proteomic 2	3 months	Changes in global protein phosphorylation levels

Secondary Outcome Measures

Name	Time	Method
Epigenomic	3 months	Change in global DNA percent methylation