PPARgamma Activation by Losartan in Hypertensive Patients: The Importance of Losartan-Metabolites

The recruitment status of this study is unknown because the information has not been verified recently.

Verified July 2007 by German Heart Institute. Recruitment status was Recruiting

First Received on November 16, 2007. No Changes Posted

Sponsor:	German Heart Institute
Collaborators:	Charite University, Berlin, Germany MSD SHARP and DOHME GMBH Haar Germany
Information provided by:	German Heart Institute
ClinicalTrials.gov Identifier:	NCT00561327

Purpose

The purpose of this study is to determine whether losartan metabolites are effective in inducing PPARγ target genes in monocytes in losartan-treated patients.

Condition	Intervention
Hypertension	Drug: losartan

Study Type:	Observational
Study Design:	Time Perspective: Retrospective

Resource links provided by NLM:

MedlinePlus related topics: High Blood Pressure

Drug Information available for: Losartan Losartan potassium

U.S. FDA Resources

Further study details as provided by German Heart Institute:

Study Start Date:

September 2007

Groups/Cohorts	Assigned Interventions
A Patients chronically treated with drug losartan	Drug: losartan Daily treated with losartan 100mg for at least the past 2 months (retrospective, no new drug treatment/ intervention)
B Patients not chronically treated with losartan

Detailed Description:

The losartan metabolite EXP3179 potently induces the activity of the peroxisome proliferator-activated receptor γ (PPAR-γ) as a partial agonist in vitro. PPAR-γ is a nuclear hormone receptor and functions as a regulator of lipid- and glucose metabolism. PPAR-γ ligands improve insulin sensitivity and glucose tolerance, and reduce cardiovascular morbidity and mortality in diabetic patients.

Angiotensin II receptor 1-blocking and PPAR-γ-activating properties of losartan metabolites in patients would markedly improve the pharmacological profile of losartan by combining anti-hypertensive and highly beneficial metabolic actions. We developed the following hypothesis:

Hypertensive patients chronically treated with losartan exhibit sufficient plasma levels of EXP3179 to activate PPARγ.
PPARγ target genes are induced in monocytes from losartan-treated patients.

Eligibility

Ages Eligible for Study:	19 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age: 19-80
Sex: male or female
Prior diagnosis of treated hypertension
Treatment with losartan 100mg/daily during at least the past 2 months (n=20/ case);
or: no prior angiotensin receptor 1-blocker treatment during the last 2 months (n=10/ control).

Exclusion Criteria:

Non-steroidal anti-inflammatory drugs (exception: Acetyl salicylic acid) for the past 21 days (due to structural homologies to glitazones, and activating effects on PPARγ)
Therapy with glitazones for the past 21 days.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00561327

Contacts

Contact: Eckart Fleck, Prof	+49-30-4593-2400	fleck@dhzb.de
Contact: Philipp Stawowy, Dr	+49-30-4593-2473	stawowy@dhzb.de

Locations

Germany
German Heart Institute	Recruiting
Berlin, Germany, 13353
Contact: Eckart Fleck, Prof +49-30-4593 2400 fleck@dhzb.de
Contact: Philipp Stawowy, Dr +49-30-45932473 stawowy@dhzb.de
Principal Investigator: Eckart Fleck, Prof

Sponsors and Collaborators

German Heart Institute

Charite University, Berlin, Germany

MSD SHARP and DOHME GMBH Haar Germany

Investigators

Principal Investigator:	Eckart Fleck, Prof	German Heart Institute
Principal Investigator:	Ulrich Kintscher, Prof	Institute of Pharmacology Charite University Medicine Berlin Germany

More Information

No publications provided

ClinicalTrials.gov Identifier:	NCT00561327 History of Changes
Other Study ID Numbers:	P2132V1
Study First Received:	November 16, 2007
Last Updated:	November 16, 2007
Health Authority:	Germany: Ethics Commission

Keywords provided by German Heart Institute:

hypertension
angiotensin receptor blockers
peroxisome proliferator activated receptor gamma

Additional relevant MeSH terms:

Hypertension
Vascular Diseases
Cardiovascular Diseases
Losartan
Angiotensin Receptor Antagonists
Anti-Arrhythmia Agents

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

ClinicalTrials.gov processed this record on May 24, 2012