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Investigation of Neurovascular Coupling in Glaucoma Patients and Healthy Subjects

Primary Purpose

Glaucoma, Open-Angle, Normal Tension Glaucoma, Ocular Hypertension

Status
Recruiting
Phase
Not Applicable
Locations
Austria
Study Type
Interventional
Intervention
Fourier Domain Doppler Optical Coherence Tomography (FDOCT)
Dynamic Vessel Analyzer (DVA)
Pattern Electroretinography (pERG)
Optical coherence tomography (OCT)
Laser Speckle Flowgraphy (LSFG)
Sponsored by
Medical University of Vienna
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Glaucoma, Open-Angle

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion criteria

Patients with primary open angle glaucoma

  • Diagnosis of manifest primary open angle glaucoma defined as pathological optic disc appearance
  • Glaucoma hemifield test outside normal limits
  • Untreated IOP ≥ 21 mmHg on at least three measurements in the medical history
  • Mean deviation in the visual field test is less than or equal 10dB (for one group) OR more than 10dB (for the other group)

Patients with normal tension glaucoma

  • Diagnosis of manifest normal tension glaucoma defined as pathological optic disc appearance
  • Glaucoma hemifield test outside normal limits
  • No evidence of untreated IOP > 20 mmHg in the medical history
  • Mean deviation in the visual field is less than or equal 10dB (for one group) OR more than 10dB (for the other group)

Patients with ocular hypertension

  • Normal ophthalmic findings except presence of ocular hypertension defined as untreated IOP ≥ 21 mmHg on at least three measurements in the medical history
  • No signs of glaucomatous damage in the optic disc
  • or the glaucoma hemifield test

Healthy control subjects

  • Normal ophthalmic findings
  • IOP < 20 mmHg on least three measurements
  • No evidence of increased IOP in the medical history
  • No signs of glaucomatous damage in the optic disc
  • or the glaucoma hemifield test

Exclusion criteria

  • History of a severe medical condition as judged by the clinical investigator
  • Abuse of alcoholic beverages
  • Smoker
  • Participation in a clinical trial in the 3 weeks preceding the study
  • Exfoliation glaucoma, pigmentary glaucoma, history of acute angle closure
  • Intraocular surgery within the last 6 months
  • Ocular inflammation or infection within the last 3 months
  • History of epilepsia
  • Diabetes mellitus
  • Untreated hypertension with systolic blood pressure > 160 mmHg, diastolic blood pressure > 95 mmHg
  • Pregnancy
  • Planned pregnancy or lactating

Sites / Locations

  • Department of Clinical Pharmacology, Medical University of ViennaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

POAG MD<10dB

POAG MD>10dB

NTG MD<10dB

NTG MD>10dB

OHT

controls

Arm Description

patients with primary open angle glaucoma with MD in visual field less than or equal 10dB

patients with primary open angle glaucoma with MD in visual field more than 10dB

patients with normal tension glaucoma with MD in visual field less than or equal 10dB

patients with normal tension glaucoma with MD in visual field more than 10dB

patients with ocular hypertension

healthy, age and sex matched, control subjects

Outcomes

Primary Outcome Measures

Flicker induced blood flow alterations
Response of retinal blood flow to flicker light

Secondary Outcome Measures

Full Information

First Posted
March 8, 2019
Last Updated
April 6, 2022
Sponsor
Medical University of Vienna
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1. Study Identification

Unique Protocol Identification Number
NCT03870230
Brief Title
Investigation of Neurovascular Coupling in Glaucoma Patients and Healthy Subjects
Official Title
Investigation of Neurovascular Coupling in Glaucoma Patients and Healthy Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 1, 2017 (Actual)
Primary Completion Date
March 2023 (Anticipated)
Study Completion Date
March 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of Vienna

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Glaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs) leading to optic nerve head (ONH) damage and associated visual field defects. The main risk factor for glaucoma is elevated intraocular pressure (IOP). Reducing IOP slows down the progression of the disease as several large multicenter trials have shown. Some patients, however, still progress despite adequately controlled IOP. As such, there is considerable interest in approaches that rescue RGCs independent of IOP, a strategy called neuroprotection. Although this field was actively discovered in the last 20 years in the brain and the eye, no non-IOP related treatment is clinically available to date. Various approaches are currently studied in some detail. One interesting strategy focuses on the neurovascular unit. The blood flow of the human retina is controlled by complex mechanisms that include myogenic, metabolic and hormonal factors. The high consumption of oxygen in the human retina is crucial for normal functioning of the organ. As in the brain, blood flow in the retina is also controlled by neurovascular coupling. This means that the retina increases its blood flow to regions in which neurons are activated. This is done in an effort to provide more oxygen and glucose to the active neurons. In the recent years evidence has accumulated that astrocytes play a key role in mediating this vasodilator signal. In the brain, abnormalities in neurovascular coupling have been observed in diseases like stroke, hypertension, spinal-cord injury and Alzheimer's disease. This break-down of neurovascular coupling is considered to play a key role in neuronal death in these diseases. In the retina, abnormalities in neurovascular coupling have been observed in diseases as diabetes and glaucoma. Most of the data obtained in the human retina stem from a system that measures retinal vasodilatation during stimulation with flickering light. The investigators have previously shown that flicker stimulation of the retina is, however, also associated with a pronounced increase in retinal blood velocities. In this study the investigators employed laser Doppler velocimetry (LDV) for the measurement of retinal blood velocities, but this technique is not clinically applicable because it requires excellent fixation of the subject under study. In the present study, the investigators propose to use an alternative system for neurovascular coupling that they have developed recently. In this approach, the investigators use bi-directional Fourier-domain optical coherence tomography for the assessment of retinal blood flow. Optical coherence tomography (OCT) is a non-invasive optical imaging modality enabling cross-sectional tomographic in vivo visualization of internal microstructure in biological systems. In ophthalmology, OCT has become a standard tool in visualizing the retina and nowadays is considered also as a standard tool in the diagnosis of retinal disease. In the recent years, conventional time domain OCT was replaced by Fourier domain OCT providing significantly improved signal quality. This bidirectional system overcomes the limitations of previously realized techniques, which include doubtful validity and limited reproducibility. In addition, pattern ERG, multifocal ERG and oscillatory potentials will be measured to allow for concomitant assessment of neural function. The investigators seek to measure neurovascular coupling in the human retina in patients with early primary open angle glaucoma (POAG), normal tension glaucoma, ocular hypertension and a healthy control group. In order to obtain information on neurovascular coupling, both neuronal function as well as retinal blood flow need to be measured. In the present study, the investigators will employ pattern ERG, multifocal ERG as well as oscillatory potentials to assess the function of the inner retina. Retinal blood flow through major retinal arterial and venous branch vessels will be measured before, during and after flicker stimulation with the dual-beam bidirectional Fourier Domain Doppler OCT coupled to the commercially available Dynamic Vessel Analyzer (DVA) produced by IMEDOS, Jena, Germany, which provides adequate resolution to study the retinal circulation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glaucoma, Open-Angle, Normal Tension Glaucoma, Ocular Hypertension

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
POAG MD<10dB
Arm Type
Experimental
Arm Description
patients with primary open angle glaucoma with MD in visual field less than or equal 10dB
Arm Title
POAG MD>10dB
Arm Type
Experimental
Arm Description
patients with primary open angle glaucoma with MD in visual field more than 10dB
Arm Title
NTG MD<10dB
Arm Type
Experimental
Arm Description
patients with normal tension glaucoma with MD in visual field less than or equal 10dB
Arm Title
NTG MD>10dB
Arm Type
Experimental
Arm Description
patients with normal tension glaucoma with MD in visual field more than 10dB
Arm Title
OHT
Arm Type
Experimental
Arm Description
patients with ocular hypertension
Arm Title
controls
Arm Type
Experimental
Arm Description
healthy, age and sex matched, control subjects
Intervention Type
Device
Intervention Name(s)
Fourier Domain Doppler Optical Coherence Tomography (FDOCT)
Intervention Description
Retinal blood flow will be assessed using FDOCT
Intervention Type
Device
Intervention Name(s)
Dynamic Vessel Analyzer (DVA)
Intervention Description
Retinal vessel diameters and oxygen saturation will be measured with the DVA device
Intervention Type
Device
Intervention Name(s)
Pattern Electroretinography (pERG)
Intervention Description
to assess the neuronal function of the retina, pattern ERG will be performed
Intervention Type
Device
Intervention Name(s)
Optical coherence tomography (OCT)
Intervention Description
to assess the morphology of the retina, OCT will be performed
Intervention Type
Device
Intervention Name(s)
Laser Speckle Flowgraphy (LSFG)
Intervention Description
to assess retinal blood flow, LSFG will be performed
Primary Outcome Measure Information:
Title
Flicker induced blood flow alterations
Description
Response of retinal blood flow to flicker light
Time Frame
1 day

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion criteria Patients with primary open angle glaucoma Diagnosis of manifest primary open angle glaucoma defined as pathological optic disc appearance Glaucoma hemifield test outside normal limits Untreated IOP ≥ 21 mmHg on at least three measurements in the medical history Mean deviation in the visual field test is less than or equal 10dB (for one group) OR more than 10dB (for the other group) Patients with normal tension glaucoma Diagnosis of manifest normal tension glaucoma defined as pathological optic disc appearance Glaucoma hemifield test outside normal limits No evidence of untreated IOP > 20 mmHg in the medical history Mean deviation in the visual field is less than or equal 10dB (for one group) OR more than 10dB (for the other group) Patients with ocular hypertension Normal ophthalmic findings except presence of ocular hypertension defined as untreated IOP ≥ 21 mmHg on at least three measurements in the medical history No signs of glaucomatous damage in the optic disc or the glaucoma hemifield test Healthy control subjects Normal ophthalmic findings IOP < 20 mmHg on least three measurements No evidence of increased IOP in the medical history No signs of glaucomatous damage in the optic disc or the glaucoma hemifield test Exclusion criteria History of a severe medical condition as judged by the clinical investigator Abuse of alcoholic beverages Smoker Participation in a clinical trial in the 3 weeks preceding the study Exfoliation glaucoma, pigmentary glaucoma, history of acute angle closure Intraocular surgery within the last 6 months Ocular inflammation or infection within the last 3 months History of epilepsia Diabetes mellitus Untreated hypertension with systolic blood pressure > 160 mmHg, diastolic blood pressure > 95 mmHg Pregnancy Planned pregnancy or lactating
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gerhard Garhöfer, MD
Phone
004314040029810
Email
gerhard.garhoefer@meduniwien.ac.at
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gerhard Garhöfer, MD
Organizational Affiliation
Department of Clinical Pharmacology, Medical University of Vienna
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Clinical Pharmacology, Medical University of Vienna
City
Vienna
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gerhard Garhöfer, MD

12. IPD Sharing Statement

Learn more about this trial

Investigation of Neurovascular Coupling in Glaucoma Patients and Healthy Subjects

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