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
Sponsor:
Collaborators:
Charite University, Berlin, Germany
MSD SHARP and DOHME GMBH Haar Germany
Information provided by:
German Heart Institute
ClinicalTrials.gov Identifier:
NCT00561327
First received: November 16, 2007
Last updated: NA
Last verified: July 2007
History: No changes posted
  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:


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:

  1. Hypertensive patients chronically treated with losartan exhibit sufficient plasma levels of EXP3179 to activate PPARγ.
  2. 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 April 17, 2014