Mechanisms of Ramipril Reduction in the Onset of Type 2 Diabetes - Full Text View

Sponsor:	Vanderbilt University
Collaborator:	King Pharmaceuticals
Information provided by:	Vanderbilt University
ClinicalTrials.gov Identifier:	NCT00574834

Purpose

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.

Condition	Intervention
Metabolic Syndrome	Drug: Ramipril Drug: HCTZ-hydrochlorothiazide Drug: Ramipril+HCTZ

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment
Official Title:	Mechanisms of Ramipril Reduction in the Onset of Type 2 Diabetes

Resource links provided by NLM:

MedlinePlus related topics: Diabetes

Drug Information available for: Hydrochlorothiazide Ramipril

U.S. FDA Resources

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:

Insulin Sensitivity [ Time Frame: 6 hours ] [ Designated as safety issue: No ]

Estimated Enrollment:	48
Study Start Date:	March 2007
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Ramipril: Active Comparator Patients randomized to 6 months treatment of Ramipril.	Drug: Ramipril Ramipril 20 mg once daily for 6 months
HCTZ: Active Comparator PAtients randomized to 6 months treatment of HCTZ.	Drug: HCTZ-hydrochlorothiazide HCTZ 25 mg once daily for 6 months
Ramipril+HCTZ: Active Comparator Patients randomized to 6 months treatment of Ramipril+HCTZ.	Drug: Ramipril+HCTZ Ramipril 20 mg and HCTZ 25 mg, both once daily for 6 months

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, 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.

Eligibility

Ages Eligible for Study:	20 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00574834

Contacts

Contact: Vanessa J. Briscoe, PhD, ANP	615-936-1824	vanessa.j.briscoe@vanderbilt.edu
Contact: Donna B. Tate, MS	615-936-1824	donna.tate@vanderbilt.edu

Locations

United States, Tennessee
Vanderbilt University	Recruiting
Nashville, Tennessee, United States, 37232
Contact: Vanessa J. Briscoe, PhD, ANP 615-936-1824 vanessa.j.briscoe@vanderbilt.edu

Sponsors and Collaborators

Vanderbilt University

King Pharmaceuticals

Investigators

Principal Investigator:

Stephen N. Davis, MD, FRCP

Vanderbilt University

More Information

No publications provided

Responsible Party:	Vanderbilt University ( Stephen N. Davis, MD )
Study ID Numbers:	IRB#070154-Ramipril, vumc33289
Study First Received:	December 13, 2007
Last Updated:	June 23, 2009
ClinicalTrials.gov Identifier:	NCT00574834 History of Changes
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Metabolic Diseases
Disease
Molecular Mechanisms of Pharmacological Action
Sodium Chloride Symporter Inhibitors
Diuretics
Physiological Effects of Drugs
Diabetes Mellitus
Endocrine System Diseases
Enzyme Inhibitors
Cardiovascular Agents
Antihypertensive Agents
Hydrochlorothiazide

Pharmacologic Actions
Ramipril
Protease Inhibitors
Membrane Transport Modulators
Pathologic Processes
Natriuretic Agents
Therapeutic Uses
Syndrome
Diabetes Mellitus, Type 2
Angiotensin-Converting Enzyme Inhibitors
Glucose Metabolism Disorders

ClinicalTrials.gov processed this record on February 08, 2010