Ocular Hemodynamic Effects of Nitrovasodilators in Healthy Subjects

Official Title: “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.

Intervention(s) in this Clinical Trial

• Drug: Nitroglycerin
  • intravenous infusion; 0, 0.125, 0.25, 0.5, 1 and 2 µg/kg/min; 20 minutes per infusion step
• Drug: Isosorbide-Dinitrate
  • intravenous infusion; 0, 0.5, 1, 2, 4, and 6 µg/kg/min; 20 minutes per infusion step
• Drug: Sodium-nitroprusside
  • intravenous infusion; 0, 0.25, 0.5, 1, 2, and 4 µg/kg/min; 20 minutes per infusion step
• Drug: Physiologic saline solution (control substance)
  • intravenous infusion, infusion period 120 minutes

Arms, Groups and Cohorts in this Clinical Trial

• 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
• 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
• 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
• Placebo Comparator: 4
  • Physiologic saline solution

Primary Measures

• Optic disc blood flow (laser Doppler flowmetry)
  • Time Frame: in total 24x on 4 study days
    Safety Issue?: No

Secondary Measures

• Intraocular pressure
  • Time Frame: in total 8x in 4 study days
    Safety Issue?: No
• Choroidal blood flow (laser Doppler flowmetry)
  • Time Frame: in total 24x on 4 study days
    Safety Issue?: No
• Fundus pulsation amplitude in the macula (laser interferometry)
  • Time Frame: in total 24x on 4 study days
    Safety Issue?: No
• Fundus pulsation amplitude in the optic disc (laser interferometry)
  • Time Frame: in total 24x on 4 study days
    Safety Issue?: No
• Blood pressure, pulse rate
  • Time Frame: on 4 study days
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 19 Years

Maximum Age for this Clinical Trial: 35 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: Medical University of Vienna Other

Overall Clinical Trial Officials and Contacts

Hans-Georg Eichler, MD Principal Investigator Department of Clinical Pharmacology, Medical University of Vienna  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00810381

Study ID Number: OPHT-211097

ClinicalTrials.gov Identifier: NCT00810381

Health Authority: Austria: Agency for Health and Food Safety