Mechanisms of Ramipril Reduction in the Onset of Type 2 Diabetes

Metabolic Syndrome Clinical Trial

Official title:

Mechanisms of Reduced Ramipril on the Onset of Type 2 Diabetes Mellitis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00574834
• Other study ID #: HP-00044872-Ramipril
• Status: Terminated
• Phase: Early Phase 1
• Start date: March 2007
• Est. completion date: August 2014

Study information

• Verified date: September 2019
• Source: University of Maryland, Baltimore
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 17
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Metabolic Syndrome

Intervention

Drug:
• Ramipril
Ramipril 20 mg once daily for 6 months
• HCTZ-hydrochlorothiazide
HCTZ 25 mg once daily for 6 months
• Ramipril+HCTZ
Ramipril 20 mg and HCTZ 25 mg, both once daily for 6 months

Locations

Country	Name	City	State
United States	University of Maryland, Baltimore	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
University of Maryland, Baltimore	King Pharmaceuticals is now a wholly owned subsidiary of Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in Insulin Sensitivity	Measures of change in endogenous glucose production from baseline to final 30 minutes of clamp studies after 6 months of treatment.	6 months