Ocular Hemodynamic Effects of Nitrovasodilators in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Glaucoma
• Intervention / Treatment: Drug: Nitroglycerin; Drug: Isosorbide-Dinitrate; Drug: Sodium-nitroprusside; Drug: Physiologic saline solution (control substance)

• Study Type: Interventional
• Enrollment (Actual): 14
• 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: 19 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; 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; intravenous infusion; 0, 0.125, 0.25, 0.5, 1 and 2 µg/kg/min; 20 minutes per infusion step
Active Comparator: 2; 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; intravenous infusion; 0, 0.5, 1, 2, 4, and 6 µg/kg/min; 20 minutes per infusion step
Active Comparator: 3; 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; intravenous infusion; 0, 0.25, 0.5, 1, 2, and 4 µg/kg/min; 20 minutes per infusion step
Placebo Comparator: 4; Physiologic saline solution	Drug: Physiologic saline solution (control substance); intravenous infusion, infusion period 120 minutes

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Hans-Georg Eichler, MD, Department of Clinical Pharmacology, Medical University of Vienna

Study record dates

Study Major Dates

• Study Start: January 1, 1999
• Primary Completion (Actual): June 1, 1999
• Study Completion (Actual): June 1, 1999

Study Registration Dates

• First Submitted: December 17, 2008
• First Submitted That Met QC Criteria: December 17, 2008
• First Posted (Estimate): December 18, 2008

Study Record Updates

• Last Update Posted (Estimate): December 18, 2008
• Last Update Submitted That Met QC Criteria: December 17, 2008
• Last Verified: December 1, 2008

More Information

Terms related to this study

• Keywords: Laser-Doppler Flowmetry; Nitroglycerin; Isosorbide Dinitrate; Choroidal blood flow; Nitrovasodilators; ONH blood flow; Sodium nitroprusside; Regional Blood Flow
• Additional Relevant MeSH Terms: Eye Diseases; Ocular Hypertension; Glaucoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Nitric Oxide Donors; Nitroglycerin; Isosorbide; Isosorbide Dinitrate; Isosorbide-5-mononitrate; Nitroprusside
• Other Study ID Numbers: OPHT-211097