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

Sponsor:	University of Maryland
Collaborator:	King Pharmaceuticals
Information provided by:	University of Maryland
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 (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.

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

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Prevention
Official Title:	Mechanisms of Reduced Ramipril on the Onset of Type 2 Diabetes Mellitis

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 2 Metabolic Syndrome

Drug Information available for: Hydrochlorothiazide Ramipril

U.S. FDA Resources

Further study details as provided by University of Maryland:

Primary Outcome Measures:

Changes in Insulin Sensitivity [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	48
Study Start Date:	March 2007
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

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

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.

Eligibility

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

Criteria

Inclusion:

48 (24 male / 24 female) with impaired glucose tolerance.
Impaired blood glucose values as outlined by the American Diabetes Association guideline. Fasting plasma glucose between 100 and 126 mg/dl or 2 hour post prandial glucose between 140 and 200 mg/dl
BMI > 25 kgM2
Age: 20-65 years
Treated or Untreated hypertension defined as measurement of seated BP at screening visit of systolic BP 120 to 150 and/ or diastolic BP 80 to 100.

Exclusion:

Patients receiving agents that can increase or lower blood glucose, i.e., metformin, thiazolidinediones, sulfonylureas, glitinides, acarbose, GLP-1 receptor agonists
Untreated or treated while seated Systolic Blood pressure >150and/or Diastolic Blood pressure >100
Taking hypertensive medications of HCTZ or ACE/ARB
Allergy to HCTZ, heparin, nitroglycerin or lidocaine
History of allergy or unacceptable side effects from ACE inhibitors
Pregnancy or intent to become pregnant during the study
Smoking
Subject unable to give voluntary informed consent

Physical Exam Exclusion Criteria

Clinically significant Cardiac Abnormalities (e.g. Heart Failure, Arrhythmia) from history or ECG in subjects > 40 years old
Pneumonia
Hepatic Failure/Jaundice
Renal Failure
Acute Cerebrovascular/ Neurological deficit
Fever greater than 38.0 C

Screening Laboratory Tests Exclusion Criteria according to protocol

Contacts and Locations

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

Contacts

Contact: Donna B. Tate

410-706-5643

dtate@medicine.umaryland.edu

Locations

United States, Maryland
University of Maryland, Baltimore	Recruiting
Baltimore, Maryland, United States, 21201
Contact: Donna B. Tate 410-706-5643 dtate@medicine.umaryland.edu

Sponsors and Collaborators

University of Maryland

King Pharmaceuticals

Investigators

Principal Investigator:

Stephen N. Davis, MD, FRCP

University of Maryland

More Information

No publications provided

Responsible Party:	Stephen N. Davis, MD, University of Maryland, Baltimore
ClinicalTrials.gov Identifier:	NCT00574834 History of Changes
Other Study ID Numbers:	HP-00044872-Ramipril
Study First Received:	December 13, 2007
Last Updated:	February 15, 2011
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Diabetes Mellitus, Type 2
Metabolic Syndrome X
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin Resistance
Hyperinsulinism
Hydrochlorothiazide
Ramipril
Diuretics
Natriuretic Agents

Physiological Effects of Drugs
Pharmacologic Actions
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012