Clinical trial NCT00152698: Effect of Irbesartan on Endothelial Function of the Retinal Vasculature in Patients With Hypercholesterolemia
Official title: A Randomised, Double-blind, Placebo-controlled, Phase III Trial to Study the Effect of Irbesartan on Endothelial Function of the Retinal Vasculature in Patients With Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Hypercholesterolemia
Lead sponsor: University of Erlangen-Nürnberg Medical School
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2005-09-09
Enrollment: 0
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The retinal vasculature is morphologically and functionally related to the cerebral vessels due to its common origin from the internal carotid artery. A recent study demonstrated that endothelium-dependent vasodilation of the retinal vasculature is impaired in patients with essential hypertension, which is a strong risk factor for stroke. Furthermore, AT1-receptor blockade was demonstrated to improve retinal endothelium-dependent vasodilation in these hypertensive patients. Hypercholesterolemia is also a risk factor for ischemic stroke and impairment of endothelial function has been observed in various vascular beds in hypercholesterolemic patients, including the coronary and the forearm vasculature. Whether endothelial function of the retinal vasculature is impaired in patients with hypercholesterolemia has not yet been investigated. In patients with stroke, AT1-receptor blockade and angiotensin-converting enzyme inhibition have beneficial effects on clinical outcome. Alterations of endothelial function of the cerebral vasculature might be one pathogenetic factor for the beneficial clinical outcome. To further address this issue, the present study was designed to test the hypothesis that endothelium-dependent vasodilation of the retinal vasculature is impaired in hypercholesterolemic patients and that endothelial function can be improved by AT1-receptor blockade.

Detailed description: see above

Eligibility criteria: Inclusion Criteria:

* Male patients aged 18-65 years with LDL-cholesterol \>= 130mg/dl
* Male healthy control subjects aged 18-65 years

Exclusion Criteria:

* All kinds of secondary hyperlipidemia.
* Advanced damage of vital organs (grades III and IV retinopathy)
* Lipid-lowering drugs (including lipid lowering dietary supplements or food additives) within the last 4 weeks
* History of serious hypersensitivity reaction to AT1-receptor blockers
* Actual or anamnestic alcohol- or drug abuse.
* Smokers or ex-smokers \< 1 year.
* Patients with Diabetes mellitus (oral medication or insulin).
* Patients with arterial fibrillation or AV-Block (II° or more).
* Patients with anamnestic myocardial infarction.
* Patients with instable angina pectoris including EcG-aberrations or cardiac insufficiency NYHA III or IV.
* History of malignancy (unless a documented disease-free period exceeding 10 years is present) with the exception of basal cell carcinoma of the skin
* History of allograft transplantation
* Patients with anaphylaxis or known therapy resistance of the used test matters
* Therapy with not approved concomitant medication, or participation in a clinical study within 4 weeks preceding treatment start.
* Disease which interfere with the pharmacodynamics and pharmacokinetics of the study drug.
* Liver or kidney disease with SGOT, GPT, g-GT, AP, bilirubin and creatinin above 200% of standard.
* Patients, who are not sufficiently compliant, or patients, who are not capable or willing to appear for controlling visits.
* Presumed risk of transmission of HIV or hepatitis via blood from the proband

Primary outcomes:
measure: Comparison of retinal endothelial function between hypercholesterolemic patients and healthy control subjects
Secondary outcomes:
measure: Effect of AT1-receptor blockade on retinal endothelial function in hypercholesterolemic patients
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: CRC, Medizinsiche Klinik 4, Nephrology and Hypertension, University of Erlangen-Nürnberg
state: Bavaria
Study officials:
affiliation: CRC, Medizinische Klinik 4, Nephrology and Hypertension, University of Erlangen-Nürnberg
name: Roland E Schmieder, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kannenkeril D, Bosch A, Harazny J, Karg M, Jung S, Ott C, Schmieder RE. Early vascular parameters in the micro- and macrocirculation in type 2 diabetes. Cardiovasc Diabetol. 2018 Sep 19;17(1):128. doi: 10.1186/s12933-018-0770-4.
citation: Bosch AJ, Harazny JM, Kistner I, Friedrich S, Wojtkiewicz J, Schmieder RE. Retinal capillary rarefaction in patients with untreated mild-moderate hypertension. BMC Cardiovasc Disord. 2017 Dec 21;17(1):300. doi: 10.1186/s12872-017-0732-x.
citation: Jumar A, Harazny JM, Ott C, Kistner I, Friedrich S, Schmieder RE. Improvement in Retinal Capillary Rarefaction After Valsartan Treatment in Hypertensive Patients. J Clin Hypertens (Greenwich). 2016 Nov;18(11):1112-1118. doi: 10.1111/jch.12851. Epub 2016 Jun 16.