Changes After Angiotensin Converting Enzyme (ACE) Inhibitor Replacement by Angiotensin II Receptor Type I (AT1) Blocker (ADIRAS)

This study is currently recruiting participants.

Verified September 2011 by Slovak Academy of Sciences

Sponsor:

Information provided by (Responsible Party):

Stefan Zorad, Slovak Academy of Sciences

ClinicalTrials.gov Identifier:

NCT01444833

First received: September 19, 2011

Last updated: September 29, 2011

Last verified: September 2011

History of Changes

Purpose

It is supposed that the significant metabolic effects (improvement of insulin sensitivity) of hypertension therapy with renin-angiotensin system (RAS) blockers in humans are mediated mainly via changes in abdominal adipose tissue. This project is aimed to confirm the hypothesis that increased concentrations of circulatory angiotensin II after angiotensin II receptor type I (AT1) blockade leads, via stimulation of angiotensin II receptor type II (AT2), to activation of adipogenesis and improvement of insulin sensitivity. Therefore, in hypertensive patients, the components of RAS and the parameters of insulin sensitivity on systemic (in plasma) and local (in adipose tissue and in its interstitial fluid) level will be studied. The main aim of the study is to identify the changes occurring in patient before and 6 months after the conversion of therapy from angiotensin converting enzyme (ACE) inhibitors to AT1 receptor blockers. Observed parameters will include gene expression of RAS components, parameters of insulin sensitivity, amount, and cellularity of adipose tissue obtained by biopsy, evaluation of direct production of cytokines and angiotensins into the interstitial fluid of fat tissue obtained by microdialysis and evaluation of the selected parameters in plasma.

Condition	Intervention
Hypertension	Drug: Candesartan

Study Type:	Interventional
Study Design:	Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Molecular - Genetic Alterations in Adipose Tissue After Change in Therapy From ACE Inhibitors to AT1 Receptor Blockers in Patients With Essential Hypertension

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Medicines High Blood Pressure

Drug Information available for: Candesartan Candesartan cilexetil

U.S. FDA Resources

Further study details as provided by Slovak Academy of Sciences:

Primary Outcome Measures:

Systemic Insulin Sensitivity after Replacement of ACE Inhibitor by AT1 Blocker [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Oral glucose tolerance test (OGTT) will be used to determine systemic insulin sensitivity.

Secondary Outcome Measures:

Adipocyte Diameter from Subcutaneous Adipose Tissue after Replacement ACE Inhibitor by AT1 Blocker [ Time Frame: 6 months ] [ Designated as safety issue: No ]
The tissue obtai ned by biopsy will be digested by collagenase and the diameter of isolated adipocytes will be evaulated by light microscopy.

Estimated Enrollment:	35
Study Start Date:	October 2008
Estimated Study Completion Date:	December 2012
Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Intervention Details:

32 mg per day duration 6 months

Other Name: Atacand

Show Detailed Description

Eligibility

Ages Eligible for Study:	25 Years to 50 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

essential hypertension
ACE inhibitors

Exclusion Criteria:

diabetes mellitus
endocrinopathies
no smokers

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01444833

Contacts

Contact: Stefan Zorad, Dr.	00421 2 54772800 ext 250	stefan.zorad@savba.sk
Contact: Adrian Oksa, MD.	00421 2 59370 ext 628	adrian.oksa@szu.sk

Locations

Slovakia
Institute of Experimental Endocrinology, SAS	Recruiting
Bratislava, Slovakia, 833 06
Contact: Stefan Zorad, Dr. 00421 2 54772800 ext 250 stefan.zorad@savba.sk
Contact: Adela Penesova, MD. 00421 2 54772800 ext 260 adela.penesova@savba.sk
Principal Investigator: Richard Imrich, MD.
Principal Investigator: Katarina Krskova, Dr.
Principal Investigator: Miroslav Vlcek, MD.
Sub-Investigator: Adrian Oksa, MD.

Sponsors and Collaborators

Slovak Academy of Sciences

Investigators

Principal Investigator:

Stefan Zorad, Dr.

Institute of Experimental Endocrinology SAS

More Information

Publications:

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Oksa A, Gajdos M, Fedelesová V, Spustová V, Dzúrik R. Effects of angiotensin-converting enzyme inhibitors on glucose and lipid metabolism in essential hypertension. J Cardiovasc Pharmacol. 1994 Jan;23(1):79-86.

Pinterova L, Krizanova O, Zorad S. Rat epididymal fat tissue express all components of the renin-angiotensin system. Gen Physiol Biophys. 2000 Sep;19(3):329-34.

Pintérová L, Zelezná B, Ficková M, Macho L, Krizanová O, Jezová D, Zórad S. Elevated AT1 receptor protein but lower angiotensin II-binding in adipose tissue of rats with monosodium glutamate-induced obesity. Horm Metab Res. 2001 Dec;33(12):708-12.

Rieusset J, Touri F, Michalik L, Escher P, Desvergne B, Niesor E, Wahli W. A new selective peroxisome proliferator-activated receptor gamma antagonist with antiobesity and antidiabetic activity. Mol Endocrinol. 2002 Nov;16(11):2628-44. Erratum in: Mol Endocrinol 2002 Dec;16(12):2745.

Responsible Party:	Stefan Zorad, Head of Laboratory, Slovak Academy of Sciences
ClinicalTrials.gov Identifier:	NCT01444833 History of Changes
Other Study ID Numbers:	MinHealth, 2007/27-SAV-02
Study First Received:	September 19, 2011
Last Updated:	September 29, 2011
Health Authority:	Slovak Republic: Ethics Committee

Keywords provided by Slovak Academy of Sciences:

hypertension
obesity
metabolism
angiotensin

Additional relevant MeSH terms:

Hypertension
Vascular Diseases
Cardiovascular Diseases
Angiotensin-Converting Enzyme Inhibitors
Candesartan
Candesartan cilexetil
Protease Inhibitors
Enzyme Inhibitors

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on May 23, 2013

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