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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00559286
Recruitment Status : Terminated (logistic reasons, patients could not be recruited)
First Posted : November 16, 2007
Last Update Posted : January 29, 2009
Heidelberg University
Information provided by:
RWTH Aachen University

Brief 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.

Condition or disease Intervention/treatment Phase
Arterial Hypertension Diabetes Mellitus Type 2 IRC or NIR Drug: Telmisartan Phase 4

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  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Influence of the Angiotensin Receptor Blocker Telmisartan on the Red Blood Cell Function and the Microcirculatory Perfusion
Study Start Date : December 2007
Actual Primary Completion Date : January 2009
Actual Study Completion Date : January 2009

Resource links provided by the National Library of Medicine

Drug Information available for: Telmisartan

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

Primary Outcome Measures :
  1. 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 :
  1. Improvement of microcirculatory perfusion (using laser doppler measurement) [ Time Frame: after 30 days treatment ]
  2. Improvement of endothelial function (using ultrasound measurements during flow mediated dilation) [ Time Frame: after 30 days treatment ]
  3. Increase in the total blood born NO pool (using reductive gase phase chemiluminescence [ Time Frame: after 30 days treatment ]
  4. Decrease of RBC aggregation (using Laser assisted optical rotational cell analyzer (Lorrca) [ Time Frame: after 30 days of treatment ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00559286

University Hospital
Aachen, NRW, Germany, 52074
Sponsors and Collaborators
RWTH Aachen University
Heidelberg University
Principal Investigator: Malte Kelm, MD, Univ.Prof. Department of Cardiology, Angiology, Pulmonary Diseases and cardiologic critical care Identifier: NCT00559286     History of Changes
Other Study ID Numbers: AIX-MK-01
EUDRA CT No 2007-002765-12
First Posted: November 16, 2007    Key Record Dates
Last Update Posted: January 29, 2009
Last Verified: January 2009

Keywords provided by RWTH Aachen University:
RBC function
NO metabolism
AT receptor blocker

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Vascular Diseases
Cardiovascular Diseases
Angiotensin Receptor Antagonists
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Molecular Mechanisms of Pharmacological Action