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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified July 2007 by German Heart Institute.
Recruitment status was:  Recruiting
Charite University, Berlin, Germany
Information provided by:
German Heart Institute Identifier:
First received: November 16, 2007
Last updated: NA
Last verified: July 2007
History: No changes posted
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
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)
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.

Ages Eligible for Study:   19 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: NCT00561327

Contact: Eckart Fleck, Prof +49-30-4593-2400
Contact: Philipp Stawowy, Dr +49-30-4593-2473

German Heart Institute Recruiting
Berlin, Germany, 13353
Contact: Eckart Fleck, Prof    +49-30-4593 2400   
Contact: Philipp Stawowy, Dr    +49-30-45932473   
Principal Investigator: Eckart Fleck, Prof         
Sponsors and Collaborators
German Heart Institute
Charite University, Berlin, Germany
Principal Investigator: Eckart Fleck, Prof German Heart Institute
Principal Investigator: Ulrich Kintscher, Prof Institute of Pharmacology Charite University Medicine Berlin Germany
  More Information Identifier: NCT00561327     History of Changes
Other Study ID Numbers: P2132V1
Study First Received: November 16, 2007
Last Updated: November 16, 2007

Keywords provided by German Heart Institute:
angiotensin receptor blockers
peroxisome proliferator activated receptor gamma

Additional relevant MeSH terms:
Vascular Diseases
Cardiovascular Diseases
Anti-Arrhythmia Agents
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action processed this record on September 21, 2017