Ocular Hemodynamic Effects of Nitrovasodilators in Healthy Subjects

Study Overview
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Brief Summary
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Glaucoma, one of the most common causes of blindness, is associated with increased intraocular pressure (IOP) and optic nerve head ischemia. Nitrovasodilators are discussed in the treatment of glaucoma. Nitrates relax smooth muscle cells in the vasculature by liberating the vasodilator nitric oxide. The IOP lowering potential and the vasodilator action in retinal and choroidal vessels of nitrates is still a matter of controversy. Previous studies on the ocular hemodynamic effects of nitrates showed partially contradicting results. In addition the IOP lowering effect of nitrates is still unclear. However, recent studies show that long acting nitrates may preserve optic nerve deterioration and visual field loss. Therefore, the role of nitrovasodilators in control of ocular blood flow and intraocular pressure has to be elucidated. For this purpose the investigators plan to test the hypothesis that nitrovasodilators improve ocular blood supply to the optic nerve head at doses which do not affect systemic hemodynamics.

Official Title
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Ocular Hemodynamic Effects of Nitrovasodilators in Healthy Subjects

Conditions
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Glaucoma

Intervention / Treatment
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* Drug: Nitroglycerin
* Drug: Isosorbide-Dinitrate
* Drug: Sodium-nitroprusside
* Drug: Physiologic saline solution (control substance)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men aged between 19 and 35 years, nonsmokers Body mass index between 15th and 85th percentile (Must et al. 1991) Normal findings in the medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant Normal laboratory values unless the investigator considers an abnormality to be clinically irrelevant Normal ophthalmic findings, ametropia < 3 Dpt. 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 Symptoms of a clinically relevant illness in the 3 weeks before the first study day History of hypersensitivity to the trial drug or to drugs with a similar chemical structure History or presence of gastrointestinal, liver or kidney disease, or other conditions known to interfere with, distribution, metabolism or excretion of study drugs History of migraine Blood donation during the previous 3 weeks

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

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: 1<br>Nitroglycerin: (Perlinganit, Nycomet Heilmittelwerke, Vienna, Austria): 0, 0.25, 0.5, 1, 1.5 and 2 µg/kg/min, each infusion step for 20 minutes | Drug: Nitroglycerin<br>* intravenous infusion; 0, 0.125, 0.25, 0.5, 1 and 2 µg/kg/min; 20 minutes per infusion step<br>|
| Active Comparator: 2<br>Isosorbide-Dinitrate: (Isoket 0,1 %, Gebro Broschek, Fieberbrunn, Austria): 0, 0.5, 1, 2, 4 and 6 µg/kg/min , each infusion step for 20 minutes | Drug: Isosorbide-Dinitrate<br>* intravenous infusion; 0, 0.5, 1, 2, 4, and 6 µg/kg/min; 20 minutes per infusion step<br>|
| Active Comparator: 3<br>Sodium-Nitroprusside: (Nipruss, Sanol-Schwarz, Monheim, Germany): 0, 0.25, 0.5, 1, 2 and 4 µg/kg/min, each infusion step for 20 minutes | Drug: Sodium-nitroprusside<br>* intravenous infusion; 0, 0.25, 0.5, 1, 2, and 4 µg/kg/min; 20 minutes per infusion step<br>|
| Placebo Comparator: 4<br>Physiologic saline solution | Drug: Physiologic saline solution (control substance)<br>* intravenous infusion, infusion period 120 minutes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optic disc blood flow (laser Doppler flowmetry) |  | in total 24x on 4 study days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intraocular pressure |  | in total 8x in 4 study days | 
| Choroidal blood flow (laser Doppler flowmetry) |  | in total 24x on 4 study days | 
| Fundus pulsation amplitude in the macula (laser interferometry) |  | in total 24x on 4 study days | 
| Fundus pulsation amplitude in the optic disc (laser interferometry) |  | in total 24x on 4 study days | 
| Blood pressure, pulse rate |  | on 4 study days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nitrovasodilators, ONH blood flow, Choroidal blood flow, Nitroglycerin, Isosorbide Dinitrate, Sodium nitroprusside, Laser-Doppler Flowmetry, Regional Blood Flow