Effect of the Known Antihypertensive Drug Telmisartan on Red Blood Cells and Circulation in the Smallest Blood Vessels
Information source: RWTH Aachen University
Information obtained from ClinicalTrials.gov on November 03, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Arterial Hypertension; Diabetes Mellitus Type 2 IRC or NIR
Intervention: Telmisartan (Drug)
Phase: Phase 4
Status: Not yet recruiting
Sponsored by: RWTH Aachen University Official(s) and/or principal investigator(s):
Malte Kelm, MD, Univ.Prof., Principal Investigator, Affiliation: Department of Cardiology, Angiology, Pulmonary Diseases and cardiologic critical care
Overall contact:
Malte Kelm, MD, Univ.Prof., Phone: +49-241-8089301, Email: mkelm@ukaachen.de
Summary
The hypothesis of the presented study is: Telmisartan induces an increase of eNOS activity in
RBC resulting in an enhanced intravascular NO bioavailability, an ameliorated RBC
deformability and a reduction of RBC and platelet aggregation. This could be a potential
mechanism of the improvement of microcirculatory disorders, especially in patients with
diabetes mellitus and arterial hypertension, treated with Telmisartan.
Clinical Details
Official title: Influence of the Angiotensin Receptor Blocker Telmisartan on the Red Blood Cell Function and the Microcirculatory Perfusion
Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Dose Comparison, Parallel Assignment, Efficacy Study
Primary outcome: Changes in Elongation-Index (EI)
Method: To determine the elongation index (EI) we use the Laser assisted optical rotational cell analyzer (Lorrca).
Secondary outcome: Improvement of microcirculatory perfusion (using laser doppler measurement)Improvement of endothelial function (using ultrasound measurements during flow mediated dilation) Increase in the total blood born NO pool (using reductive gase phase chemiluminescence Decrease of RBC aggregation (using Laser assisted optical rotational cell analyzer (Lorrca)
Detailed description:
Recently, it could be shown that the renin-angiotensin-system (RAS) influences different
signal transduction pathways within the red blood cells (RBC). This includes the Na+/H+
exchange activity, the Ca2+-ATP-ase mediated Ca2+efflux, the erythropoietin- dependent
production of RBC, the RBC deformability, RBC aggregation and the interaction of RBC and
platelets. Recent studies and experiments, done by our group, focus on the oxidative and
nitrosative metabolism of NO within the blood. The interactions of the RAS and endothelial NO
are well known and described in detail. Based on a wide experience in this research field of
NO metabolism, we characterized recently an active endothelial-type NO-synthase in RBC on the
biochemical, functional and molecular level. Erythrocyte-derived NO formation serves
important regulatory functions essential for adequate passage of blood through the
vasculature. Here we aimed to treat patients with diabetes mellitus and arterial hypertension
with Telmisartan as an angiotensin receptor antagonist. Efficacy parameters studied in this
study should be: i) RBC deformability, RBC aggregation, ii) RBC dependent production of
nitric oxide as well as detection of eNOS activity in RBC and iii) indices of
microcirculatory perfusion. This project could broaden the view of effects of Telmisartan in
the treatment of microcirculatory disorders in patients with diabetes mellitus and arterial
hypertension, who exhibit a reduced NO bioavailability and RBC function.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Male.
Criteria:
Inclusion Criteria:
- Men older than 18 years
- Diabetes mellitus type 2 defined according to the criteria of the American Diabetes
Association Arterial hypertension defined according to the criteria of the Joint
National Committtees (JNC 7)
- Given informed consent
Exclusion Criteria:
- Serve heart failure
- Serve aortic valve stenosis or hypertrophy obstructive cardiomyopathy
- Relevant cardiac arrhythmias
- Acute myocardial infarction within the last 4 weeks
- renal failure
- bilateral renal artery stenosis
- liver diseases
- primary hyperaldosteronism
- orthostatic hypotension (systolic blood pressure <100mmHg)
- hypokalemia, hyponatremia, hypercalcemia, symptomatic hyperuricemia
- inflammatory disease
- malignant disease
- previous intolerance to AT1 receptor antagonists and/or sulfonamides
- current therapy with insulin sensitizer
- current therapy with digoxin
- known abuse of alcohol or drugs
Locations and Contacts
Malte Kelm, MD, Univ.Prof., Phone: +49-241-8089301, Email: mkelm@ukaachen.de
University Hospital, Aachen, NRW 52074, Germany
Additional Information
Starting date: December 2007
Ending date: December 2008
Last updated: August 13, 2008
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