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

NCT00644475 | Unknown Phase 3

• 1 other identifier: UNIPV001DIM2008
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Essential Hypertension

Keywords

Hypertension; Insulin sensitivity; Fibrinolysis

Outcome Measures

Primary Outcomes (3)

• PAI-1 level and t-PA activity time course changes

  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

  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

  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 Outcomes (1)

• Blood pressure changes

  At 0, 1, 2, 4, 8, and 12 weeks

Study Arms (2)

2

EXPERIMENTAL

Imidapril

Drug: Imidapril

1

ACTIVE COMPARATOR

Candesartan

Drug: Candesartan

Interventions

Imidapril DRUG

tablets; 5, 10, 15, 20 mg; od; 12 weeks

Also known as: Not yet registered in Italy

2

Candesartan DRUG

tablets; 8, 16, 24, and 32 mg; od; 12 weeks

Also known as: Registered in Italy

1

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pavia: lead

Study Sites (1)

University of Pavia

Pavia, 27100, Italy

RECRUITING

MeSH Terms

Conditions

Essential Hypertension; Hypertension; Insulin Resistance

Interventions

imidapril; candesartan

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Giuseppe Derosa, MD

  University of Pavia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Giuseppe Derosa, MD

CONTACT

+39 0382 502614; giuseppe.derosa@unipv.it

Roberto Fogari, MD

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 12, 2008
• First Posted: March 26, 2008
• Study Start: March 1, 2008
• Primary Completion: March 1, 2008
• Study Completion: March 1, 2009
• Last Updated: March 26, 2008

Record last verified: 2008-03

Locations

IT (1)