|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.
|Early Phase 1
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
- 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
|August 2014 (Final data collection date for primary outcome measure)
- 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.
- 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
- 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
- Hepatic Failure/Jaundice
- Renal Failure
- Acute Cerebrovascular/ Neurological deficit
- Fever greater than 38.0 C
Screening Laboratory Tests Exclusion Criteria according to protocol
|Sexes Eligible for Study:||All|
|20 Years to 65 Years (Adult, Older Adult)
|Contact information is only displayed when the study is recruiting subjects|
|Stephen N. Davis, MBBS, University of Maryland, Baltimore
|University of Maryland, Baltimore
|King Pharmaceuticals is now a wholly owned subsidiary of Pfizer
|Principal Investigator:||Stephen N. Davis, MD, FRCP||University of Maryland, Baltimore|
|University of Maryland, Baltimore