Role of Endothelin- and Nitric Oxide-System in the Regulation of Optic Nerve Head Blood Flow During Changes in Ocular Perfusion Pressure

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by Medical University of Vienna.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT00406731
First received: November 30, 2006
Last updated: June 2, 2009
Last verified: June 2009
  Purpose

Autoregulation is the ability of a vascular bed to maintain blood flow despite changes in perfusion pressure. The existence of an effective autoregulation in the optic nerve circulation has been shown in animals and humans. The exact mechanism behind this autoregulation is still unknown. The motive for the investigation of optic nerve head (ONH) blood flow autoregulation is to enhance the understanding of pathologic eye conditions associated with ocular vascular disorders. To clarify the regulatory mechanisms of ONH microcirculation is of critical importance to understand the pathophysiology of glaucoma because there is evidence that glaucoma is associated with optic nerve head ischemia. Several studies indicate that a disturbed autoregulation might contribute to glaucomatous optic neuropathy. Previous findings suggest endothelial dysfunction in glaucomatous optic neuropathy, in particular alterations in endothelin- and nitric oxide- system, which both play an important role in local regulation of vascular tone.

In the present study, changes in ocular perfusion pressure will be performed during administration of drugs, which may potentially alter the pressure-flow relationship. These drugs include endothelin-1 and the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA).


Condition Intervention Phase
Ocular Physiology
Optic Disk
Regional Blood Flow
Drug: NG-monomethyl-L-arginine (L-NMMA)
Drug: Endothelin-1 (ET-1)
Drug: Physiologic saline solution (placebo control)
Device: Laser Doppler flowmetry
Device: Goldmann applanation tonometer
Device: HP-CMS patient monitor
Procedure: Suction cup method
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Role of Endothelin-and Nitric Oxide-System in the Regulation of Optic Nerve Head Blood Flow During Changes in Ocular Perfusion Pressure

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • ONH pressure-flow relationship [ Time Frame: in total 6x on 3 study days ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: January 2008
Estimated Study Completion Date: November 2009
Estimated Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: NG-monomethyl-L-arginine (L-NMMA)
    bolus 6 mg/kg over 5 minutes followed by a continuous intravenous infusion of 60 µg/kg/min over 12 minutes; twice on 1 study day
    Drug: Endothelin-1 (ET-1)
    5 ng/kg/min intravenous infusion over 17 minutes; twice on 1 study day
    Drug: Physiologic saline solution (placebo control)
    intravenous infusion over 20 minutes; twice on 1 study day
    Device: Laser Doppler flowmetry
    blood flow measurements at the temporal neuroretinal rim of the optic nerve head
    Device: Goldmann applanation tonometer
    Intraocular pressure measurements
    Device: HP-CMS patient monitor
    blood pressure and pulse rate measurements
    Procedure: Suction cup method
    The IOP will be raised by an 11 mm diameter, standardized suction cup placed on the temporal sclera with the anterior edge at least 1 mm from the limbus.
  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Men aged between 18 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, ametropy < 1 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 systemic or pulmonary hypertension, or other cardiac or pulmonary diseases
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00406731

Contacts
Contact: Gerhard Garhoefer, MD +43 40 400 2981 gerhard.garhoefer@meduniwien.ac.at

Locations
Austria
Department of Clinical Pharmacology, Medical University of Vienna Recruiting
Vienna, Austria, 1090
Sponsors and Collaborators
Medical University of Vienna
Investigators
Principal Investigator: Gabriele Fuchsjaeger-Mayrl, MD,Univ.Doz. Department of Clinical Pharmacology, Medical University of Vienna
  More Information

No publications provided

Responsible Party: Gabriele Fuchsjaeger-Mayrl, MD, Department of Clinical Pharmacology, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT00406731     History of Changes
Other Study ID Numbers: OPHT-080206
Study First Received: November 30, 2006
Last Updated: June 2, 2009
Health Authority: Austria: Agency for Health and Food Safety

Keywords provided by Medical University of Vienna:
Endothelin-1
L-NG-Monomethyl Arginine
Optic Nerve Head blood flow

Additional relevant MeSH terms:
Nitric Oxide
Omega-N-Methylarginine
Anti-Asthmatic Agents
Antioxidants
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Endothelium-Dependent Relaxing Factors
Enzyme Inhibitors
Free Radical Scavengers
Gasotransmitters
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Respiratory System Agents
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on October 23, 2014