Impact of Non-Exudative Type 1 MNV on AMD Progression

Age-Related Macular Degeneration Clinical Trial

Official title:

The Impact of Non-Exudative Type 1 Macular Neovascularization (MNV) on Age-related Macular Degeneration (AMD) Progression

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06125977
• Other study ID #: IRB_00151913
• Secondary ID: 1R01EY033365-01A
• Status: Recruiting
• Start date: January 30, 2023
• Est. completion date: August 2027

Study information

• Verified date: November 2023
• Source: University of Utah
• Contact: Christine Glasmann
• Phone: 801-585-6667
• Email: christine.glasmann[@]hsc.utah.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The overall goal of the proposed research project is to provide evidence that a specific subtype of neovascularization that may develop in eyes with age-related macular degeneration (AMD) prevents vision loss.

This concept challenges the current view that the development of neovascularizations in AMD represents a harmful event in general. Notably, before the era of anti-vascular endothelial growths factor (VEGF) therapy, destruction and surgical removal of neovascular membranes have been tested as treatment options for neovascular AMD.

This research project aims to substantiate the hypothesis that type 1 macular neovascularization (MNV) is intrinsically protective, in sense of a positive response to the degenerative processes in AMD. This concept has actually been proposed by pathologists decades ago but has not been systematically investigated in vivo.

With the immense advances in retinal imaging, 'sub-clinical', non-exudative type 1 MNVs that are located beneath the retinal pigment epithelium (RPE) can now be detected non-invasively and characterized in vivo. There is currently a growing body of evidence that photoreceptor and RPE degeneration is indeed slowed down in eyes exhibiting type 1 MNV. However, the proof of a direct protective effect of non-exudative type 1 MNV on visual function in AMD is lacking.

Here, the aim is to demonstrate relative preservation of function along with preserved structure in the immediate vicinity of type 1 MNV, while there is progressive loss of sensitivity and degeneration in the surrounding tissue.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 88
• Est. completion date: August 2027
• Est. primary completion date: August 2027
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Males and females aged 50 years and older of all ethnicities.

• Intermediate AMD in at least one eye (study eye) with the following criteria (to be confirmed by UREAD Reading Center at the Screening and Baseline Visit):

• Large drusen >125 microns and definite hyperpigmentary abnormalities associated with medium (> 63 microns and <= 125 microns) or large drusen.

• Treatment-naive, non-exudative type 1 macular neovascularization (MNV) in the study eye (to be confirmed by the Utah Retinal Reading Center (UREAD) at the Screening and Baseline Visit):

• localized presence of a dense vascular network between Bruch's membrane and retinal pigment epithelium (RPE) on optical coherence tomography angiography (OCT-A) and a double-layer / shallow irregular RPE elevation (SIRE) sign on structural OCT without previous treatment or signs of exudation.

• MNV lesion size between one disc area (2.54 mm2) and a maximum of 5 disc areas (12.7 mm2).

• MNV lesion does not exceed the image frame of the 9x9 OCT-A scan.

• Sufficiently clear ocular media, adequate pupillary dilatation, and adequate fixation to permit quality fundus imaging and fundus-controlled perimetry (FCP) testing.

• Ability to comply with study protocol timelines.

Exclusion Criteria:

• Atrophy in the study eye defined as

• Complete RPE and outer retinal atrophy (cRORA) on OCT with Homogeneous choroidal hypertransmission

• Absence of the RPE band measuring > 250 microns

• Evidence of overlying photoreceptor degeneration whose features include outer nuclear layer thinning, external limiting membrane loss, and ellipsoid zone or interdigitation zone loss

• Incomplete RPE and outer retinal atrophy (iRORA) on OCT with Region of signal hypertransmission into the choroid (< 250µm)

• Corresponding zone of attenuation or disruption of the RPE

• Evidence of overlying photoreceptor degeneration.

• Signs of exudation defined as serous detachment of the sensory retina, intraretinal cystoid fluid, or subretinal/retinal hemorrhage in the study eye.

• Any history of treatment of exudative MNV in the study eye (e.g. type 1, type 2, mixed, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation); Note: Non-exudative type 1 MNV in the study eye is NOT an exclusion criterion; non-exudative or exudative MNV in the fellow eye is not an exclusion criterion. Fellow-eyes may receive treatment of exudative MNV as part of clinical care.

• Any disease/disorder other than AMD in the study eye at the time of inclusion (e.g.

• monogenic retinal diseases, diabetic retinopathy, retinal detachment, previous retinal surgeries, myopic degeneration), uncontrolled glaucoma with intraocular pressure (IOP) of higher than 30 mmHg (despite current pharmacological or non-pharmacological treatment) and uveitis.

• History of central retinal laser treatment, including photodynamic therapy (PDT) and subthreshold laser treatment for AMD in the study eye.

• Cataract surgery in the study eye within the last three months prior to enrollment. Laser posterior capsulotomy in the study eye within the last 2 weeks prior to enrollment.

• Current or previous participation in clinical trials investigating drugs or supplements in AMD (except vitamins and minerals).

• Current or previous participation (less than 3 months from termination of participation) in clinical trials investigating drugs or supplements in diseases other than AMD.

• Any concurrent ocular condition in the study eye (e.g. cataracts) that, in the opinion of the investigator, requires medical or surgical intervention during the study period to prevent or treat visual loss that might result from that condition or, if allowed to progress untreated, could likely contribute to loss of at least two Snellen equivalent lines of best-corrected visual acuity during the study period.

• Concomitant diseases that in the opinion of the investigator would make adherence to the examination schedule difficult or unlikely (e.g. personality disorder, chronic alcoholism, Alzheimers Disease, drug abuse).

• Evidence of significantly uncontrolled concomitant diseases at the discretion of the investigator (e.g. cardiovascular, neurological, pulmonary, renal, hepatic, endocrine gastrointestinal disorder).

Related Conditions & MeSH terms

• Age-Related Macular Degeneration
• Choroidal Neovascularization
• Macular Degeneration
• Neovascularization, Choroidal
• Neovascularization, Pathologic

Locations

Country	Name	City	State
United States	University of Utah	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
University of Utah	National Eye Institute (NEI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean change in mesopic retinal sensitivity assessed by Fundus-controlled Perimetry (FCP).	This sensitivity change will be compared between (I) retinal areas colocalizing with non-exudative type 1 MNV (test-point group I) and (II) retinal areas without evidence of MNV (testpoint group II).	At months 36 from baseline.
Secondary	Changes over time of qualitative and quantitative structural biomarkers for disease progression.	These changes will be compared between (I) retinal areas co-localizing with non-exudative type 1 MNV and (II) retinal areas without evidence of MNV.	At months 36 from baseline.
Secondary	Mean change over time in dark-adapted retinal sensitivity assessed by Fundus-controlled Perimetry (FCP).	This sensitivity change will be compared between (I) retinal areas colocalizing with non-exudative type 1 MNV (test-point group I) and (II) retinal areas without evidence of MNV (testpoint group II).	At months 36 from baseline.