Role of Endothelin-1 in Optic Nerve Head Blood Flow Regulation During Isometric Exercise in Healthy Humans

Autoregulation is defined as the ability of a vascular bed to adapt its vascular resistance to changes in perfusion pressure. In the eye, several studies have reported that retinal blood flow is autoregulated over a wide range of ocular perfusion pressures. The investigators could recently show that Endothelin-1 is a key metabolite in the regulation of vascular tone in the eye and plays an important role in the blood flow autoregulation of the choroidal circulation. However, no data is yet available for the optic nerve head. Thus, the present study is designed to test the hypothesis that Endothelin-1 plays also a role in optic nerve head blood flow autoregulation.

Therefore, subjects will perform squatting to increase systemic perfusion pressure during administration of either an endothelin A-receptor blocker (BQ-123) or placebo. Optic nerve head blood flow will be continuously measured during the procedure to investigate optic nerve head autoregulation.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: BQ-123; Drug: Physiological saline solution; Device: Laser Doppler Flowmetry; Device: Goldmann Applanation Tonometer; Other: squatting

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Department of Clinical Pharmacology, Medical University of Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women aged between 18 and 35 years, nonsmokers
• Men and women will be included in equal parts
• Normal findings in the medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant
• Normal findings in the laboratory testings unless the investigator considers an abnormality to be clinically irrelevant
• Normal ophthalmic findings, ametropia less than 3 diopters

Exclusion Criteria:

• Regular use of medication, abuse of alcoholic beverages, participation in a clinical trial in the 3 weeks preceding the study
• Treatment in the previous 3 weeks with any drug (except intake of oral contraceptives)
• Symptoms of a clinically relevant illness in the 3 weeks before the first study day
• History or presence of gastrointestinal, liver or kidney disease, or other conditions known to interfere with distribution, metabolism or excretion of study drugs
• Blood donation during the previous 3 weeks
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Physiological saline solution	Drug: BQ-123; 60 mcg/min, infusion period: 60 min; Drug: Physiological saline solution; infusion period 60 minutes; Device: Laser Doppler Flowmetry; blood flow measurements at the temporal neuroretinal rim to assess optic nerve head blood flow; Device: Goldmann Applanation Tonometer; intraocular pressure measurements; Other: squatting; subjects will perform squatting for 6 minutes while blood flow measurements
Active Comparator: BQ-123	Drug: BQ-123; 60 mcg/min, infusion period: 60 min; Drug: Physiological saline solution; infusion period 60 minutes; Device: Laser Doppler Flowmetry; blood flow measurements at the temporal neuroretinal rim to assess optic nerve head blood flow; Device: Goldmann Applanation Tonometer; intraocular pressure measurements; Other: squatting; subjects will perform squatting for 6 minutes while blood flow measurements

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Optic nerve head pressure-flow relationship	1 year

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Gabriele Fuchsjaeger-Mayrl, MD, Univ.Doz, Department of Clinical Pharmacology, Medical University of Vienna

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: June 1, 2009
• First Submitted That Met QC Criteria: June 4, 2009
• First Posted (Estimate): June 5, 2009

Study Record Updates

• Last Update Posted (Estimate): August 10, 2012
• Last Update Submitted That Met QC Criteria: August 9, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Intraocular Pressure; BQ-123; Optic Disk; Regional Blood Flow; Ocular Physiology; Optic Nerve Head Blood Flow
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Endothelin Receptor Antagonists; cyclo(Trp-Asp-Pro-Val-Leu)
• Other Study ID Numbers: OPHT-320708