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Mechanisms of Ramipril Reduction in the Onset of Type 2 Diabetes

Primary Purpose

Metabolic Syndrome

Status
Terminated
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ramipril
HCTZ-hydrochlorothiazide
Ramipril+HCTZ
Sponsored by
University of Maryland, Baltimore
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Metabolic Syndrome

Eligibility Criteria

20 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • University of Maryland, Baltimore

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Ramipril

HCTZ

Ramipril+HCTZ

Arm Description

Patients randomized to 6 months treatment of Ramipril.

PAtients randomized to 6 months treatment of HCTZ.

Patients randomized to 6 months treatment of Ramipril+HCTZ.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
December 13, 2007
Last Updated
September 10, 2019
Sponsor
University of Maryland, Baltimore
Collaborators
King Pharmaceuticals is now a wholly owned subsidiary of Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT00574834
Brief Title
Mechanisms of Ramipril Reduction in the Onset of Type 2 Diabetes
Official Title
Mechanisms of Reduced Ramipril on the Onset of Type 2 Diabetes Mellitis
Study Type
Interventional

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Terminated
Why Stopped
Lack of funding
Study Start Date
March 2007 (undefined)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
August 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Maryland, Baltimore
Collaborators
King Pharmaceuticals is now a wholly owned subsidiary of Pfizer

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metabolic Syndrome

7. Study Design

Primary Purpose
Prevention
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ramipril
Arm Type
Active Comparator
Arm Description
Patients randomized to 6 months treatment of Ramipril.
Arm Title
HCTZ
Arm Type
Active Comparator
Arm Description
PAtients randomized to 6 months treatment of HCTZ.
Arm Title
Ramipril+HCTZ
Arm Type
Active Comparator
Arm Description
Patients randomized to 6 months treatment of Ramipril+HCTZ.
Intervention Type
Drug
Intervention Name(s)
Ramipril
Other Intervention Name(s)
Altace
Intervention Description
Ramipril 20 mg once daily for 6 months
Intervention Type
Drug
Intervention Name(s)
HCTZ-hydrochlorothiazide
Other Intervention Name(s)
Brand Names: HydroDIURIL, Microzide
Intervention Description
HCTZ 25 mg once daily for 6 months
Intervention Type
Drug
Intervention Name(s)
Ramipril+HCTZ
Other Intervention Name(s)
Altace and HydroDIURIL, Microzide
Intervention Description
Ramipril 20 mg and HCTZ 25 mg, both once daily for 6 months
Primary Outcome Measure Information:
Title
Changes in Insulin Sensitivity
Description
Measures of change in endogenous glucose production from baseline to final 30 minutes of clamp studies after 6 months of treatment.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen N. Davis, MD, FRCP
Organizational Affiliation
University of Maryland, Baltimore
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Maryland, Baltimore
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States

12. IPD Sharing Statement

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Mechanisms of Ramipril Reduction in the Onset of Type 2 Diabetes

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