Official Title: “Mechanisms of Ramipril Reduction in the Onset of Type 2 Diabetes”

The study will be focused on determining the integrated in-vivo mechanisms responsible for Ramipril's effects on delaying type 2 diabetes and restoring normal glycemia in patients with impaired glucose tolerance.

Hypothesis - Ramipril effects will delay the onset of type 2 diabetes and restore normal glycemia in patients with impaired glucose tolerance.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment

Study Primary Completion Date: August 2009

Several studies have demonstrated that therapeutic agents used to reduce glucose levels and/or weight can delay the onset of type 2 diabetes. Intriguingly, modulation of the rennin-angiotensin-system by either angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) also result in reduction in the onset of type 2 DM. The most striking effect was found with Ramipril in the HOPE study. The onset of new type 2 DM was reduced by 34% (p<0.001) as compared to placebo. Furthermore, the results of the DREAM trial demonstrate that Ramipril at a dose of 15 mg can significantly reverse impaired glucose tolerance. However, the mechanisms underlying Ramipril effects to delay type 2 diabetes are not known.

The proposal will be focused on determining the integrated in-vivo mechanisms responsible for Ramipril's effects on delaying type 2 DM and restoring normo glycemia in patients with impaired glucose tolerance.

The specific aims of the project are: - to determine the effect of Ramipril on insulin resistance at the level of the liver and peripheral tissues, - to determine the effect of Ramipril on endothelial function, - to determine the effects of Ramipril on insulin secretion, and - to determine the effects of Ramipril on substrate flux, lipolysis and inflammatory cytokines.

Intervention(s) in this Clinical Trial

• Drug: Ramipril
  • Ramipril 20 mg once daily for 6 months
• Drug: HCTZ-hydrochlorothiazide
  • HCTZ 25 mg once daily for 6 months
• Drug: Ramipril+HCTZ
  • Ramipril 20 mg and HCTZ 25 mg, both once daily for 6 months

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Ramipril
  • Patients randomized to 6 months treatment of Ramipril.
• Active Comparator: HCTZ
  • PAtients randomized to 6 months treatment of HCTZ.
• Active Comparator: Ramipril+HCTZ
  • Patients randomized to 6 months treatment of Ramipril+HCTZ.

Primary Measures

• Insulin Sensitivity
  • Time Frame: 6 hours
    Safety Issue?: No

Inclusion Criteria:

• 48 (24 male / 24 female) with impaired glucose tolerance
• Fasting plasma glucose between 100 and 126 mg/dl or post prandial glucose between 140 and 200 mg/dl
• BMI greater than 25 kgM2
• Age: 20-65 years

Exclusion Criteria:

• Patients receiving agents that can increase or lower blood glucose, i.e., metformin, thiazolidinediones, sulfonylureas, glitinides, acarbose, GLP-1 receptor agonists
• Current ACE or ARB therapy
• Pregnancy or intent to become pregnant during the study
• Smoking

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 20 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Vanderbilt University

Overall Clinical Trial Officials and Contacts

Stephen N. Davis, MD, FRCP Principal Investigator Vanderbilt University  

Overall Contact: Vanessa J. Briscoe, PhD, ANP 615-936-1824 vanessa.j.briscoe@vanderbilt.edu

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00574834

Study ID Number: IRB#070154-Ramipril

ClinicalTrials.gov Identifier: NCT00574834

Health Authority: United States: Institutional Review Board