Mechanisms of Ramipril Reduction in the Onset of Type 2 Diabetes

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Maryland
Sponsor:
Collaborator:
King Pharmaceuticals is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
Stephen N. Davis, University of Maryland
ClinicalTrials.gov Identifier:
NCT00574834
First received: December 13, 2007
Last updated: May 27, 2014
Last verified: May 2014
  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:


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 2015
Estimated Primary Completion Date: December 2015 (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 is now a wholly owned subsidiary of Pfizer
Investigators
Principal Investigator: Stephen N. Davis, MD, FRCP University of Maryland, Baltimore County
  More Information

No publications provided

Responsible Party: Stephen N. Davis, Professor, University of Maryland
ClinicalTrials.gov Identifier: NCT00574834     History of Changes
Other Study ID Numbers: HP-00044872-Ramipril
Study First Received: December 13, 2007
Last Updated: May 27, 2014
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 July 26, 2014