Clinical Investigation on the Blood Oxygenation at the Optic Nerve Head in Fabry Patients

Fabry Disease Clinical Trial

Official title:

Clinical Investigation on the Blood Oxygenation at the Optic Nerve Head in Relation With Visual Field Loss in Fabry Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02023086
• Other study ID #: GZ-2012-10918
• Status: Completed
• Phase: N/A
• First received: December 10, 2013
• Last updated: May 1, 2017
• Start date: August 2014
• Est. completion date: September 2016

Study information

• Verified date: May 2017
• Source: Université de Montréal
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

This study aims to evaluate blood oxygenation at the optic nerve head in relation with visual field losses observed in many Fabry patients. Data collected will allow to evaluate if there is a link between these two entities.

Study will last up to 2 years during which a limited number of Fabry patients will be compared to a control group to confirm any relationship between blood flow and field losses, and to see if these results vary over time.

HYPOTHESIS

1. Fabry patients will present significant differences in visual fields compared to control 2 There will be variability of the visual field defects on the long term but not on the short term 3 Blood oxygenation will be higher for Fabry patients 4 Blood volume at the optic nerve head will be the same for both groups.

Description:

The first subjects who meet the following criteria will be enrolled in the study.

Inclusion criteria (Fabry group ):

• Aged over 18 years old

• Being diagnosed with Fabry disease

• 3 subjects will be under enzyme replacement treatment for the treatment of Fabry disease.

• 3 subjects will not receive enzyme replacement treatment

• Is fit to give legal consent.

• Is available for a period of 2 years

Inclusion criteria (CONTROL group ):

• Matched for age and sex with group A - 6 participants

• Being healthy, with no known chronic systemic disease nor acute disease at the moment of the recruitment

• Is fit to give legal consent.

• Is available for a period of 2 years

Exclusion criteria (Both groups):

• Presents with an active pathological ocular condition

• Presence of an abnormal optic nerve (congenital or acquired)

• Usage of topical ocular drug(s) at the time of selection

• To have known allergy to topical diagnostic drugs used in this study

• Usage of systemic medication with known effect on the visual field

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Inclusion criteria (Fabry group):

• Aged over 18 years old

• Being diagnosed with Fabry disease

• 3 subjects will be under enzyme replacement treatment for the treatment of Fabry disease.

• 3 subjects will not receive enzyme replacement treatment

• Is fit to give legal consent.

• Is available for a period of 2 years

Inclusion criteria (CONTROL group):

• Matched for age and sex with group A - 6 participants

• Being healthy, with no known chronic systemic disease nor acute disease at the moment of the recruitment

• Is fit to give legal consent.

• Is available for a period of 2 years

Exclusion Criteria:( both groups):

• Presents with an active pathological ocular condition

• Presence of an abnormal optic nerve (congenital or acquired)

• Usage of topical ocular drug(s) at the time of selection

• To have known allergy to topical diagnostic drugs used in this study

• Usage of systemic medication with known effect on the visual field

Related Conditions & MeSH terms

• Fabry Disease

Intervention

Procedure:
• Contrast sensitivity measurement
Contrast sensitivity test is made with targets alternating black and white lines. The larger the lines are, easier it is to see them. Targets are distributed in 5 rows, each oriented at a different angle. Contrast sensitivity level is determined by the smallest target seen by the participant, line by line. This test is done under dim lightning with the habitual visual correction worn.
• Slit Lamp assessment and intra-ocular pressure measurement
Slit lamp is used to assess the presence of significant lens opacities known as Fabry cataracts. In fact, these opacities can induced a bias on the contrast sensitivity measurement and can increase the symptoms felt by the patient. A grade 2 (CFDI grading chart) of lens opacities is considered clinically significant and this will become an exclusion criteria for the following of the study. Intra-ocular pressure will be measured with a non contact tonometer (air pulsed) (Ocular Response Analyser, Reichert Instrumentation.)
• Visual field testing
Visual field will be assessed with an automated perimeter (Humphrey, Texas) using a threshold strategy. This implies that the subject has to identify not only if he perceives the visual stimulus but the minimal level of this stimulus (in decibels), to be seen, is also recorded. Visual field will be tested up to 30 degrees from the central point of fixation. In order to measure immediate variability of the visual testing among Fabry subjects, this test will be done at the beginning of the testing session (in the morning) and another time 1h00 later.
• Oxygen flow at the optic nerve head measurement
Pupils will be dilated with 1 drop of 1% tropicamide. The procedure is similar to the one used for taking a photo of the retina. Each measurement session represents a continuous recording of 20 simultaneous functions of reflectometry from the optic nerve area during 10 seconds. During all recording sessions, the systemic arterial oxygen saturation will be also monitored at the right index finger using a pulse oximeter (Escort M10, Invivo, Orlando, USA). Arterial blood pressure will be also monitored before and after the testing using a manual sphygmomanometer.

Drug:
• Tropicamide
Used to dilate patient's pupil during testing

Device:
• OSOME
The OSOME system is the only technology able to perform on line and real time capillaries blood oxygenation measurement in the eye. The system operates with 1200 discreet wavelengths between 400 nm to 700 nm with 500 millisecond integration times. It is not invasive, functioning just like a fundus camera.

Locations

Country	Name	City	State
Canada	Universite de Montreal	Montreal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Université de Montréal	Genzyme, a Sanofi Company

Country where clinical trial is conducted

Canada, 

References & Publications (4)

Diaconu V. Multichannel spectroreflectometry: a noninvasive method for assessment of on-line hemoglobin derivatives. Appl Opt. 2009 Apr 1;48(10):D52-61. — View Citation

Feke GT, Riva CE. Laser Doppler measurements of blood velocity in human retinal vessels. J Opt Soc Am. 1978 Apr;68(4):526-31. — View Citation

Kumagai K, Mitamura Y, Mizunoya S, Fujimoto N, Yamamoto S. A case of anterior ischemic optic neuropathy associated with Fabry's disease. Jpn J Ophthalmol. 2008 Sep-Oct;52(5):421-3. doi: 10.1007/s10384-008-0572-4. Epub 2008 Nov 11. — View Citation

Pitz S, Grube-Einwald K, Renieri G, Reinke J. Subclinical optic neuropathy in Fabry disease. Ophthalmic Genet. 2009 Dec;30(4):165-71. doi: 10.3109/13816810903148004. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood oxygenation at the optic nerve head	To evaluate blood oxygenation and blood volume optical density at the different optic nerve head zones in Fabry patients, presenting field defects, and to compare the results to a control group.	up to 2 years
Secondary	Origin of visual field defect in Fabry patients	To validate that visual field defects found in Fabry patients could be vascular in origin. AND To demonstrate that visual field testing should be included in the standard eye examination and follow-up of patients with Fabry	up to 2 years

External Links

•   web site of the School of Optometry University of Montreal