Mechanisms of Ramipril Reduction in the Onset of Type 2 Diabetes
Information source: University of Maryland
Information obtained from ClinicalTrials.gov on December 08, 2011
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Metabolic Syndrome
Intervention: Ramipril (Drug); HCTZ-hydrochlorothiazide (Drug); Ramipril+HCTZ (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: University of Maryland Official(s) and/or principal investigator(s):
Stephen N. Davis, MD, FRCP, Principal Investigator, Affiliation: University of Maryland
Overall contact:
Donna B. Tate, Phone: 410-706-5643, Email: dtate@medicine.umaryland.edu
Summary
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.
Clinical Details
Official title: Mechanisms of Reduced Ramipril on the Onset of Type 2 Diabetes Mellitis
Study design: Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
Primary outcome: Changes in Insulin Sensitivity
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
Minimum age: 20 Years.
Maximum age: 65 Years.
Gender(s): Both.
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
Locations and Contacts
Donna B. Tate, Phone: 410-706-5643, Email: dtate@medicine.umaryland.edu
University of Maryland, Baltimore, Baltimore, Maryland 21201, United States; Recruiting
Donna B. Tate, Phone: 410-706-5643, Email: dtate@medicine.umaryland.edu
Additional Information
Starting date: March 2007
Last updated: February 15, 2011
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