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

NCT ID: NCT00561327

Last Updated: 2007-11-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Study Classification

OBSERVATIONAL

Study Start Date

2007-09-30

Brief Summary

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

Detailed Description

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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.

Conditions

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Hypertension

Keywords

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hypertension angiotensin receptor blockers peroxisome proliferator activated receptor gamma

Study Design

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Study Time Perspective

RETROSPECTIVE

Study Groups

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A

Patients chronically treated with drug losartan

losartan

Intervention Type DRUG

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

No interventions assigned to this group

Interventions

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losartan

Daily treated with losartan 100mg for at least the past 2 months (retrospective, no new drug treatment/ intervention)

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

19 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Charite University, Berlin, Germany

OTHER

Sponsor Role collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

German Heart Institute

OTHER

Sponsor Role lead

Principal Investigators

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Eckart Fleck, Prof

Role: PRINCIPAL_INVESTIGATOR

German Heart Institute

Ulrich Kintscher, Prof

Role: PRINCIPAL_INVESTIGATOR

Institute of Pharmacology Charite University Medicine Berlin Germany

Locations

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German Heart Institute

Berlin, State of Berlin, Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Eckart Fleck, Prof

Role: CONTACT

Phone: +49-30-4593-2400

Email: [email protected]

Philipp Stawowy, Dr

Role: CONTACT

Phone: +49-30-4593-2473

Email: [email protected]

Facility Contacts

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Eckart Fleck, Prof

Role: primary

Philipp Stawowy, Dr

Role: backup

Other Identifiers

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P2132V1

Identifier Type: -

Identifier Source: org_study_id