Mechanisms of Ramipril Reduction in the Onset of Type 2 Diabetes

Early Phase 1

Terminated

• Conditions: Metabolic Syndrome
• Interventions: Drug: Ramipril+HCTZ; Drug: HCTZ-hydrochlorothiazide; Drug: Ramipril

• Registration Number: NCT00574834
• Lead Sponsor: University of Maryland, Baltimore

Brief Summary

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 (blood sugar levels) 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.

Detailed Description

Several studies have demonstrated that therapeutic agents used to reduce glucose levels and/or weight can delay the onset of type 2 diabetes. Intriguingly, 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 normal 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.

Study Timeline

• Study Start: 2007-03
• Study First Submitted: 2007-12-13
• Study First Submitted QC: 2007-12-13
• Study First Posted: 2007-12-17
• Primary Completion: 2014-08
• Study Completion: 2014-08
• Results First Submitted: 2015-12-10
• Results First Submitted QC: 2015-12-10
• Results First Posted: 2016-01-15
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-10
• Last Update Posted: 2019-09-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 17

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ramipril+HCTZ	Ramipril+HCTZ	Patients randomized to 6 months treatment of Ramipril+HCTZ.
HCTZ	HCTZ-hydrochlorothiazide	PAtients randomized to 6 months treatment of HCTZ.
Ramipril	Ramipril	Patients randomized to 6 months treatment of Ramipril.

Primary Outcome Measures

Name	Time	Method
Changes in Insulin Sensitivity	6 months	Measures of change in endogenous glucose production from baseline to final 30 minutes of clamp studies after 6 months of treatment.

Trial Locations

Locations (1)

University of Maryland, Baltimore; 🇺🇸 Baltimore, Maryland, United States