Ocular Hemodynamic Effects of Nitrovasodilators in Healthy Subjects

NCT00810381 | Completed DMC

• 1 other identifier: OPHT-211097
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Glaucoma

Keywords

Nitrovasodilators; ONH blood flow; Choroidal blood flow; Nitroglycerin; Isosorbide Dinitrate; Sodium nitroprusside; Laser-Doppler Flowmetry; Regional Blood Flow

Outcome Measures

Primary Outcomes (1)

• Optic disc blood flow (laser Doppler flowmetry)

  in total 24x on 4 study days

Secondary Outcomes (5)

• 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

Study Arms (4)

1

ACTIVE COMPARATOR

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

2

ACTIVE COMPARATOR

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

3

ACTIVE COMPARATOR

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

4

PLACEBO COMPARATOR

Physiologic saline solution

Drug: Physiologic saline solution (control substance)

Interventions

Nitroglycerin DRUG

intravenous infusion; 0, 0.125, 0.25, 0.5, 1 and 2 µg/kg/min; 20 minutes per infusion step

1

Isosorbide-Dinitrate DRUG

intravenous infusion; 0, 0.5, 1, 2, 4, and 6 µg/kg/min; 20 minutes per infusion step

2

Sodium-nitroprusside DRUG

intravenous infusion; 0, 0.25, 0.5, 1, 2, and 4 µg/kg/min; 20 minutes per infusion step

3

Physiologic saline solution (control substance) DRUG

intravenous infusion, infusion period 120 minutes

4

Eligibility Criteria

• Age: 19 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Department of Clinical Pharmacology, Medical University of Vienna

Vienna, 1090, Austria

Location

MeSH Terms

Conditions

Glaucoma

Interventions

Nitroglycerin; Isosorbide; Nitroprusside; Control Groups

Condition Hierarchy (Ancestors)

Ocular Hypertension; Eye Diseases

Intervention Hierarchy (Ancestors)

Nitro Compounds; Organic Chemicals; Sorbitol; Sugar Alcohols; Alcohols; Carbohydrates; Ferricyanides; Cyanides; Anions; Ions; Electrolytes; Inorganic Chemicals; Ferric Compounds; Iron Compounds; Hydrogen Cyanide; Nitrogen Compounds; Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Hans-Georg Eichler, MD

  Department of Clinical Pharmacology, Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 17, 2008
• First Posted: December 18, 2008
• Study Start: January 1, 1999
• Primary Completion: June 1, 1999
• Study Completion: June 1, 1999
• Last Updated: December 18, 2008

Record last verified: 2008-12

Locations

AU (1)