Effect of the Known Antihypertensive Drug Telmisartan on Red Blood Cells and Circulation in the Smallest Blood Vessels (ITEM)

January 28, 2009 updated by: RWTH Aachen University

Influence of the Angiotensin Receptor Blocker Telmisartan on the Red Blood Cell Function and the Microcirculatory Perfusion

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A
treatment with 80 mg Telmisartan per day for 30 days
Drug: Telmisartan
application of 80mg or 20mg Telmisartan per day for 30 days
Active Comparator: B
treatment with 20mg Telmisartan per day for 30 days
Drug: Telmisartan
application of 80mg or 20mg Telmisartan per day for 30 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
after 30 days of treatment with study drug/control

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

RWTH Aachen University

Collaborators

Bayer
Heidelberg University
CTCA

Investigators

  • Principal Investigator: Malte Kelm, MD, Univ.Prof., Department of Cardiology, Angiology, Pulmonary Diseases and cardiologic critical care

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2007

Primary Completion (Actual)

January 1, 2009

Study Completion (Actual)

January 1, 2009

Study Registration Dates

First Submitted

November 15, 2007

First Submitted That Met QC Criteria

November 15, 2007

First Posted (Estimate)

November 16, 2007

Study Record Updates

Last Update Posted (Estimate)

January 29, 2009

Last Update Submitted That Met QC Criteria

January 28, 2009

Last Verified

January 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AIX-MK-01
  • EUDRA CT No 2007-002765-12

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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