Role of Nitric Oxide in Optic Nerve Head Blood Flow Regulation During Experimental Increase of Intraocular Pressure in Healthy Humans

NCT00914394 | Terminated DMC

• 1 other identifier: OPHT-310708
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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. Large scale studies have shown that reduced ocular perfusion pressure is an important risk factor for the prevalence, the incidence and the progression of primary open angle glaucoma. Former studies that investigated ocular blood flow autoregulation focused mainly on choroidal blood flow. For the optic nerve head only few data are available, although it seems likely that it underlies similar autoregulatory mechanisms. A previous study investigating choroidal blood flow has shown that nitric oxide (NO) plays a key role in choroidal autoregulation. The present study is designed to test the hypothesis that NO plays a role in optic nerve head autoregulation during increased intraocular pressure (IOP). Therefore, IOP will be experimentally increased using a suction cup device in the absence of presence of either a nitric oxide synthase inhibitor (L-NMMA), an α-receptor agonist (phenylephrine) or placebo. Optic nerve head blood flow will be continuously measured during the procedure.

Conditions

Healthy

Keywords

L-NG-Monomethyl Arginine; Optic Nerve Head Blood Flow; Intraocular Pressure; Regional Blood Flow; Ocular Physiology; Optic Disk

Outcome Measures

Primary Outcomes (1)

• optic nerve head pressure-flow relationship

  1 year

Study Arms (3)

NG-monomethyl-L-arginine (L-NMMA)

ACTIVE COMPARATOR

Drug: NG-monomethyl-L-arginine (L-NMMA); Drug: Phenylephrine; Drug: Physiological saline solution (as placebo); Device: Laser Doppler Flowmetry; Device: Goldmann applanation tonometer; Device: Suction cup

Phenylephrine

ACTIVE COMPARATOR

Drug: NG-monomethyl-L-arginine (L-NMMA); Drug: Phenylephrine; Drug: Physiological saline solution (as placebo); Device: Laser Doppler Flowmetry; Device: Goldmann applanation tonometer; Device: Suction cup

Physiological saline solution

PLACEBO COMPARATOR

Drug: NG-monomethyl-L-arginine (L-NMMA); Drug: Phenylephrine; Drug: Physiological saline solution (as placebo); Device: Laser Doppler Flowmetry; Device: Goldmann applanation tonometer; Device: Suction cup

Interventions

NG-monomethyl-L-arginine (L-NMMA) DRUG

bolus 6mg/kg over 5 minutes followed by a continuous infusion of 60µg/kg/min over 15 minutes

NG-monomethyl-L-arginine (L-NMMA); Phenylephrine; Physiological saline solution

Phenylephrine DRUG

1µg/kg/min, infusion period 20 minutes

NG-monomethyl-L-arginine (L-NMMA); Phenylephrine; Physiological saline solution

Physiological saline solution (as placebo) DRUG

infusion period 20 minutes

NG-monomethyl-L-arginine (L-NMMA); Phenylephrine; Physiological saline solution

Laser Doppler Flowmetry DEVICE

Measurements will be performed at the neuroretinal rim to assess ONH blood flow.

NG-monomethyl-L-arginine (L-NMMA); Phenylephrine; Physiological saline solution

Goldmann applanation tonometer DEVICE

intraocular pressure measurements

NG-monomethyl-L-arginine (L-NMMA); Phenylephrine; Physiological saline solution

Suction cup DEVICE

Experimental stepwise increase of intraocular pressure while measurement of optic nerve head blood flow.

NG-monomethyl-L-arginine (L-NMMA); Phenylephrine; Physiological saline solution

Eligibility Criteria

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

You may qualify if:

• 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 1 diopter

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 (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

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Department of Clinical Pharmacology, Medical University of Vienna

Vienna, Vienna, 1090, Austria

Location

MeSH Terms

Interventions

omega-N-Methylarginine; Phenylephrine; Laser-Doppler Flowmetry

Intervention Hierarchy (Ancestors)

Arginine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Rheology; Investigative Techniques

Study Officials

• Gabriele Fuchsjaeger-Mayrl, MD, Univ.Doz.

  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
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc Prof Priv-Doz Dr

Study Record Dates

• First Submitted: June 1, 2009
• First Posted: June 5, 2009
• Study Start: October 1, 2010
• Primary Completion: July 1, 2011
• Last Updated: November 14, 2014

Record last verified: 2014-11

Locations

AU (1)