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

This study has been terminated.
(logistic reasons, patients could not be recruited)
Sponsor:
Collaborators:
CTCA
Heidelberg University
Bayer
Information provided by:
RWTH Aachen University
ClinicalTrials.gov Identifier:
NCT00559286
First received: November 15, 2007
Last updated: January 28, 2009
Last verified: January 2009
  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 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


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
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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Germany
University Hospital
Aachen, NRW, Germany, 52074
Sponsors and Collaborators
RWTH Aachen University
CTCA
Heidelberg University
Bayer
Investigators
Principal Investigator: Malte Kelm, MD, Univ.Prof. Department of Cardiology, Angiology, Pulmonary Diseases and cardiologic critical care
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00559286     History of Changes
Other Study ID Numbers: AIX-MK-01, EUDRA CT No 2007-002765-12
Study First Received: November 15, 2007
Last Updated: January 28, 2009
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:
Hypertension
Diabetes Mellitus
Diabetes Mellitus, Type 2
Vascular Diseases
Cardiovascular Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Telmisartan
Angiotensin Receptor Antagonists
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014