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

Study Overview
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Brief Summary
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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.

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

Conditions
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Healthy

Intervention / Treatment
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* Drug: BQ-123
* Drug: Physiological saline solution
* Device: Laser Doppler Flowmetry
* Device: Goldmann Applanation Tonometer
* Other: squatting


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BQ-123, Optic Nerve Head Blood Flow, Intraocular Pressure, Regional Blood Flow, Ocular Physiology, Optic Disk