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 (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.
Early Phase 1
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Investigator
Primary Purpose: Prevention
|Official Title:||Mechanisms of Reduced Ramipril on the Onset of Type 2 Diabetes Mellitis|
- Changes in Insulin Sensitivity [ Time Frame: 6 months ]Measures of change in endogenous glucose production from baseline to final 30 minutes of clamp studies after 6 months of treatment.
|Study Start Date:||March 2007|
|Study Completion Date:||August 2014|
|Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
Active Comparator: Ramipril
Patients randomized to 6 months treatment of Ramipril.
Ramipril 20 mg once daily for 6 months
Other Name: Altace
Active Comparator: HCTZ
PAtients randomized to 6 months treatment of HCTZ.
HCTZ 25 mg once daily for 6 months
Other Name: Brand Names: HydroDIURIL, Microzide
Active Comparator: Ramipril+HCTZ
Patients randomized to 6 months treatment of Ramipril+HCTZ.
Ramipril 20 mg and HCTZ 25 mg, both once daily for 6 months
Other Name: Altace and HydroDIURIL, Microzide
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00574834
|United States, Maryland|
|University of Maryland, Baltimore|
|Baltimore, Maryland, United States, 21201|
|Principal Investigator:||Stephen N. Davis, MD, FRCP||University of Maryland|