Imidapril and Candesartan on Fibrinolysis and Insulin-Sensitivity in Patients With Mild to Moderate Hypertension

March 25, 2008 updated by: University of Pavia

Randomized, Controlled, Parallel Arm, PROBE Study to Evaluate Different Effects of Imidapril and Candesartan on Fibrinolysis and Insulin-Sensitivity in Patients With Mild to Moderate Hypertension

BACKGROUND The effects of ACE-inhibitors on fibrinolysis are well documented. Experimental and clinical studies have shown that ACE inhibitors induce a reduction in plasma PAI-1 levels in many cardiovascular diseases, like hypertension, coronary heart disease, and heart failure. Their effects on t-PA are more controversial, due to the fact that t-PA exists in several forms, including free and bound to PAI-1. Indeed an increase in t-PA activity has been observed in humans and it seems related to bradykinin increase which is known to stimulate endothelial t-PA synthesis. These favourable effects on fibrinolysis could be related not only to the Angiotensin II reduction and the bradykinin increase but also to the improvement in insulin sensitivity, as insulin has been suggested as one of the main regulators of fibrinolytic activity.

To date conflicting results have been reported about the effects of ARBs on fibrinolysis. Some studies have reported small improvements, others no significant effect. These conflicting results may be due to possible methodological bias but a possible pathophysiological explanation might be that receptor subtypes other than AT1 mediate the effect of Angiotensin-II on endothelial PAI-1 expression, i.e. the AT4 receptors, and during AT1 receptor blockade there is an important increase not only of Angiotensin-II, but also of all its catabolites including Angiotensin IV. The dissimilar effects on of ACE Is and ARBs may also depend on their different action on the RAS and their different effect on insulin sensitivity: ACE-Is improve insulin sensitivity, while the majority of ARBs have been reported to have a neutral effect. Moreover, unlike ACE-Is, ARBs do not affect the metabolism of bradykinin, which is known to stimulate t-PA synthesis and release.

AIM OF THE STUDY The aim of this study is to verify the effect of imidapril compared to candesartan on insulin sensitivity, evaluated through the euglycemic hyperinsulinemic clamp, and on fibrinolysis, evaluated through the plasma PAI-1 and t-PA activity, in mild to moderate hypertensive patients.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Pavia, Italy, 27100
        • Recruiting
        • University of Pavia
        • Contact:
        • Contact:
        • Principal Investigator:
          • Giuseppe Derosa, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age 18-65 years
  • DBP ≥ 90 < 110 mmHg and SBP ≥ 140 < 180 mmHg
  • Normal Body Mass Index (BMI) (≤ 25 Kg/m2)
  • Normal kidney function (Creatinine Clearance > 80 ml/min)
  • Normocholesterolemia (TC < 250 mg/dl)

  • At least one of the following risk factor:

    • age (M > 55 years)
    • smoking
    • family history of premature CV disease
    • echocardiographic LVH
    • carotid wall thickening (IMT > 0.9 mm)
    • ankle/brachial BP < 0.9

Exclusion Criteria:

  • Secondary hypertension
  • Overweight or obese state (BMI ≥ 25 Kg/m2)
  • Suspected history of allergy to the ARBs, or ACEs
  • Malignancy
  • Renal, hepatic, endocrine, or gastrointestinal disease
  • Women who are pregnant and lactating
  • Women child-bearing potential
  • Heart failure
  • AMI and/or stroke in the previous 6 months
  • CHD
  • Diabetes mellitus

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 2
Imidapril
Drug: Imidapril
tablets; 5, 10, 15, 20 mg; od; 12 weeks
Other Names:
  • Not yet registered in Italy
Active Comparator: 1
Candesartan
Drug: Candesartan
tablets; 8, 16, 24, and 32 mg; od; 12 weeks
Other Names:
  • Registered in Italy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
PAI-1 level and t-PA activity time course changes
Time Frame: Desmopressin and Clamp venous blood samples will be taken for all patients between 08.00 and 09.00 at 0 and 12 weeks; week 0, 1, 2, 4, 8, and 12 for the others
Desmopressin and Clamp venous blood samples will be taken for all patients between 08.00 and 09.00 at 0 and 12 weeks; week 0, 1, 2, 4, 8, and 12 for the others
t-PA activity at the desmopressin test
Time Frame: Desmopressin and Clamp venous blood samples will be taken for all patients between 08.00 and 09.00 at 0 and 12 weeks; week 0, 1, 2, 4, 8, and 12 for the others
Desmopressin and Clamp venous blood samples will be taken for all patients between 08.00 and 09.00 at 0 and 12 weeks; week 0, 1, 2, 4, 8, and 12 for the others
Insulin sensitivity state through euglycemic hyperinsulinemic clamp method
Time Frame: Desmopressin and Clamp venous blood samples will be taken for all patients between 08.00 and 09.00 at 0 and 12 weeks; week 0, 1, 2, 4, 8, and 12 for the others
Desmopressin and Clamp venous blood samples will be taken for all patients between 08.00 and 09.00 at 0 and 12 weeks; week 0, 1, 2, 4, 8, and 12 for the others

Secondary Outcome Measures

Outcome Measure
Time Frame
Blood pressure changes
Time Frame: At 0, 1, 2, 4, 8, and 12 weeks
At 0, 1, 2, 4, 8, and 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pavia

Investigators

  • Principal Investigator: Giuseppe Derosa, MD, University of Pavia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2008

Primary Completion (Actual)

March 1, 2008

Study Completion (Anticipated)

March 1, 2009

Study Registration Dates

First Submitted

March 12, 2008

First Submitted That Met QC Criteria

March 25, 2008

First Posted (Estimate)

March 26, 2008

Study Record Updates

Last Update Posted (Estimate)

March 26, 2008

Last Update Submitted That Met QC Criteria

March 25, 2008

Last Verified

March 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UNIPV001DIM2008

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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