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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
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Maryland
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Baltimore, Maryland, United States, 21201
- University of Maryland, Baltimore
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: Ramipril
Patients randomized to 6 months treatment of Ramipril.
|
Ramipril 20 mg once daily for 6 months
Other Names:
|
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Active Comparator: HCTZ
PAtients randomized to 6 months treatment of HCTZ.
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HCTZ 25 mg once daily for 6 months
Other Names:
|
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Active Comparator: Ramipril+HCTZ
Patients randomized to 6 months treatment of Ramipril+HCTZ.
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Ramipril 20 mg and HCTZ 25 mg, both once daily for 6 months
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Changes in Insulin Sensitivity
Time Frame: 6 months
|
Measures of change in endogenous glucose production from baseline to final 30 minutes of clamp studies after 6 months of treatment.
|
6 months
|
Collaborators and Investigators
Investigators
- Principal Investigator: Stephen N. Davis, MD, FRCP, University of Maryland, Baltimore
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Insulin Resistance
- Hyperinsulinism
- Metabolic Syndrome
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Enzyme Inhibitors
- Protease Inhibitors
- Natriuretic Agents
- Membrane Transport Modulators
- Diuretics
- Angiotensin-Converting Enzyme Inhibitors
- Sodium Chloride Symporter Inhibitors
- Hydrochlorothiazide
- Ramipril
Other Study ID Numbers
- HP-00044872-Ramipril
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