PPARgamma Activation by Losartan in Hypertensive Patients: The Importance of Losartan-Metabolites
Information source: German Heart Institute
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hypertension
Intervention: losartan (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: German Heart Institute Official(s) and/or principal investigator(s):
Eckart Fleck, Prof, Principal Investigator, Affiliation: German Heart Institute
Ulrich Kintscher, Prof, Principal Investigator, Affiliation: Institute of Pharmacology Charite University Medicine Berlin Germany
Overall contact:
Eckart Fleck, Prof, Phone: +49-30-4593-2400, Email: fleck@dhzb.de
Summary
The purpose of this study is to determine whether losartan metabolites are effective in
inducing PPARγ target genes in monocytes in losartan-treated patients.
Clinical Details
Study design: Retrospective
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
Minimum age: 19 Years.
Maximum age: 80 Years.
Gender(s): Both.
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.
Locations and Contacts
Eckart Fleck, Prof, Phone: +49-30-4593-2400, Email: fleck@dhzb.de
German Heart Institute, Berlin 13353, Germany; Recruiting
Eckart Fleck, Prof, Phone: +49-30-4593 2400, Email: fleck@dhzb.de
Philipp Stawowy, Dr, Phone: +49-30-45932473, Email: stawowy@dhzb.de
Eckart Fleck, Prof, Principal Investigator
Additional Information
Starting date: September 2007
Last updated: November 16, 2007
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