Effect of the Known Antihypertensive Drug Telmisartan on Red Blood Cells and Circulation in the Smallest Blood Vessels - Full Text View

Sponsor:	RWTH Aachen University
Collaborators:	CTCA University of Heidelberg Bayer
Information provided by:	RWTH Aachen University
ClinicalTrials.gov Identifier:	NCT00559286

Purpose

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.

Condition	Intervention	Phase
Arterial Hypertension Diabetes Mellitus Type 2 IRC or NIR	Drug: Telmisartan	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Dose Comparison, Parallel Assignment, Efficacy Study
Official Title:	Influence of the Angiotensin Receptor Blocker Telmisartan on the Red Blood Cell Function and the Microcirculatory Perfusion

Resource links provided by NLM:

MedlinePlus related topics: Blood Pressure Medicines Diabetes High Blood Pressure

Drug Information available for: Telmisartan

U.S. FDA Resources

Further study details as provided by RWTH Aachen University:

Primary Outcome Measures:

Changes in Elongation-Index (EI) Method: To determine the elongation index (EI) we use the Laser assisted optical rotational cell analyzer (Lorrca). [ Time Frame: after 30 days of treatment with study drug/control ]

Secondary Outcome Measures:

Improvement of microcirculatory perfusion (using laser doppler measurement) [ Time Frame: after 30 days treatment ]
Improvement of endothelial function (using ultrasound measurements during flow mediated dilation) [ Time Frame: after 30 days treatment ]
Increase in the total blood born NO pool (using reductive gase phase chemiluminescence [ Time Frame: after 30 days treatment ]
Decrease of RBC aggregation (using Laser assisted optical rotational cell analyzer (Lorrca) [ Time Frame: after 30 days of treatment ]

Estimated Enrollment:	40
Study Start Date:	December 2007
Study Completion Date:	January 2009
Primary Completion Date:	January 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental treatment with 80 mg Telmisartan per day for 30 days	Drug: Telmisartan application of 80mg or 20mg Telmisartan per day for 30 days
B: Active Comparator treatment with 20mg Telmisartan per day for 30 days	Drug: Telmisartan application of 80mg or 20mg Telmisartan per day for 30 days

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00559286

Locations

Germany, NRW
University Hospital
Aachen, NRW, Germany, 52074

Sponsors and Collaborators

RWTH Aachen University

CTCA

University of Heidelberg

Bayer

Investigators

Principal Investigator:

Malte Kelm, MD, Univ.Prof.

Department of Cardiology, Angiology, Pulmonary Diseases and cardiologic critical care

More Information

No publications provided

Study ID Numbers:	AIX-MK-01, EUDRA CT No 2007-002765-12
Study First Received:	November 15, 2007
Last Updated:	January 28, 2009
ClinicalTrials.gov Identifier:	NCT00559286 History of Changes
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by RWTH Aachen University:

perfusion
microcirculation
RBC function
NO metabolism
AT receptor blocker

Additional relevant MeSH terms:

Metabolic Diseases
Molecular Mechanisms of Pharmacological Action
Diabetes Mellitus
Vascular Diseases
Endocrine System Diseases
Enzyme Inhibitors
Cardiovascular Agents
Antihypertensive Agents
Pharmacologic Actions

Protease Inhibitors
Angiotensin II Type 1 Receptor Blockers
Therapeutic Uses
Diabetes Mellitus, Type 2
Angiotensin-Converting Enzyme Inhibitors
Cardiovascular Diseases
Telmisartan
Glucose Metabolism Disorders
Hypertension

ClinicalTrials.gov processed this record on February 08, 2010