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

December 13, 2007
May 27, 2014
March 2007
December 2015   (final data collection date for primary outcome measure)
Changes in Insulin Sensitivity [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Insulin Sensitivity [ Time Frame: 6 hours ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00574834 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
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Mechanisms of Ramipril Reduction in the Onset of Type 2 Diabetes
Mechanisms of Reduced Ramipril on the Onset of Type 2 Diabetes Mellitis

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.

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.
Interventional
Not Provided
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Metabolic Syndrome
  • Drug: Ramipril
    Ramipril 20 mg once daily for 6 months
    Other Name: Altace
  • Drug: HCTZ-hydrochlorothiazide
    HCTZ 25 mg once daily for 6 months
    Other Name: Brand Names: HydroDIURIL, Microzide
  • Drug: Ramipril+HCTZ
    Ramipril 20 mg and HCTZ 25 mg, both once daily for 6 months
    Other Name: Altace and HydroDIURIL, Microzide
  • Active Comparator: Ramipril
    Patients randomized to 6 months treatment of Ramipril.
    Intervention: Drug: Ramipril
  • Active Comparator: HCTZ
    PAtients randomized to 6 months treatment of HCTZ.
    Intervention: Drug: HCTZ-hydrochlorothiazide
  • Active Comparator: Ramipril+HCTZ
    Patients randomized to 6 months treatment of Ramipril+HCTZ.
    Intervention: Drug: Ramipril+HCTZ
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
48
December 2015
December 2015   (final data collection date for primary outcome measure)

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

Both
20 Years to 65 Years
Yes
Contact: Donna B. Tate 410-706-5643 dtate@medicine.umaryland.edu
United States
 
NCT00574834
HP-00044872-Ramipril
Yes
Stephen N. Davis, University of Maryland
University of Maryland
King Pharmaceuticals is now a wholly owned subsidiary of Pfizer
Principal Investigator: Stephen N. Davis, MD, FRCP University of Maryland, Baltimore County
University of Maryland
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP