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Mechanisms of Ramipril Reduction in the Onset of Type 2 Diabetes

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ClinicalTrials.gov Identifier: NCT00574834
Recruitment Status : Terminated (Lack of funding)
First Posted : December 17, 2007
Results First Posted : January 15, 2016
Last Update Posted : March 20, 2017
Sponsor:
Collaborator:
King Pharmaceuticals is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
Stephen N. Davis, University of Maryland

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.


Condition or disease Intervention/treatment Phase
Metabolic Syndrome Drug: Ramipril Drug: HCTZ-hydrochlorothiazide Drug: Ramipril+HCTZ Early Phase 1

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 : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Mechanisms of Reduced Ramipril on the Onset of Type 2 Diabetes Mellitis
Study Start Date : March 2007
Primary Completion Date : August 2014
Study Completion Date : August 2014


Arm Intervention/treatment
Active Comparator: Ramipril
Patients randomized to 6 months treatment of Ramipril.
Drug: Ramipril
Ramipril 20 mg once daily for 6 months
Other Name: Altace
Active Comparator: HCTZ
PAtients randomized to 6 months treatment of HCTZ.
Drug: HCTZ-hydrochlorothiazide
HCTZ 25 mg once daily for 6 months
Other Name: Brand Names: HydroDIURIL, Microzide
Active Comparator: Ramipril+HCTZ
Patients randomized to 6 months treatment of Ramipril+HCTZ.
Drug: Ramipril+HCTZ
Ramipril 20 mg and HCTZ 25 mg, both once daily for 6 months
Other Name: Altace and HydroDIURIL, Microzide



Primary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   20 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00574834


Locations
United States, Maryland
University of Maryland, Baltimore
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
University of Maryland
King Pharmaceuticals is now a wholly owned subsidiary of Pfizer
Investigators
Principal Investigator: Stephen N. Davis, MD, FRCP University of Maryland

Responsible Party: Stephen N. Davis, Professor, University of Maryland
ClinicalTrials.gov Identifier: NCT00574834     History of Changes
Other Study ID Numbers: HP-00044872-Ramipril
First Posted: December 17, 2007    Key Record Dates
Results First Posted: January 15, 2016
Last Update Posted: March 20, 2017
Last Verified: February 2017

Additional relevant MeSH terms:
Metabolic Syndrome X
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Hydrochlorothiazide
Ramipril
Antihypertensive Agents
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors