Role of Nitric Oxide in Optic Nerve Head Blood Flow Regulation During Isometric Exercise in Healthy Humans

NCT00806741 | Completed DMC

• 1 other identifier: OPHT-300708
• Study Type: interventional
• Target: 18
• 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. The investigators recently showed that nitric oxide (NO) is a key metabolite in the regulation of vascular tone in the eye and plays an important role in the blood flow autoregulation of the choroidal circulation. However, no data is yet available for the optic nerve head. Thus, the present study is designed to test the hypothesis that NO plays also a role in optic nerve head blood flow autoregulation. Therefore, subjects will perform squatting to increase systemic perfusion pressure during administration 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 to investigate optic nerve head autoregulation.

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

  in total 6x on 3 study days

Study Arms (3)

1

ACTIVE COMPARATOR

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

Drug: NG-monomethyl-L-arginine (L-NMMA); Device: Laser Doppler Flowmetry; Device: Goldmann applanation tonometer; Other: squatting

2

ACTIVE COMPARATOR

Phenylephrine

Drug: Phenylephrine; Device: Laser Doppler Flowmetry; Device: Goldmann applanation tonometer; Other: squatting

3

PLACEBO COMPARATOR

Physiological saline solution

Drug: Physiological saline solution (as placebo); Device: Laser Doppler Flowmetry; Device: Goldmann applanation tonometer; Other: squatting

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

1

Phenylephrine DRUG

1μg/kg/min, infusion period 20 minutes

2

Physiological saline solution (as placebo) DRUG

infusion period 20 minutes

3

Laser Doppler Flowmetry DEVICE

blood flow measurements at the temporal neuroretinal rim of the optic nerve head

1; 2; 3

Goldmann applanation tonometer DEVICE

intraocular pressure measurements

1; 2; 3

squatting OTHER

Subjects will perform squatting for 6 minutes while blood flow is measured

1; 2; 3

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 3 diopters

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, 1090, Austria

Location

Related Publications (1)

• Schmidl D, Boltz A, Kaya S, Lasta M, Pemp B, Fuchsjager-Mayrl G, Hommer A, Garhofer G, Schmetterer L. Role of nitric oxide in optic nerve head blood flow regulation during isometric exercise in healthy humans. Invest Ophthalmol Vis Sci. 2013 Mar 15;54(3):1964-70. doi: 10.1167/iovs.12-11406.

  PMID: 23439596 DERIVED

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.

  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. PD Dr.

Study Record Dates

• First Submitted: December 10, 2008
• First Posted: December 11, 2008
• Study Start: September 1, 2009
• Primary Completion: March 1, 2010
• Study Completion: September 1, 2012
• Last Updated: November 30, 2012

Record last verified: 2012-11

Locations

AU (1)