Deciphering AMD by Deep Phenotyping and Machine Learning- Prospective Study - PINNACLE

Age-related Macular Degeneration Clinical Trial

— PINNACLE  

Official title:

Deciphering AMD by Deep Phenotyping and Machine Learning- Prospective Study - PINNACLE

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04269304
• Other study ID #: IRAS - 256931
• Secondary ID: 47270210572/Z/18
• Status: Active, not recruiting
• Start date: October 28, 2019
• Est. completion date: June 2025

Study information

• Verified date: February 2024
• Source: University of Southampton
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

We will conduct a prospective non-interventional study including 400 early AMD patients (=600 untreated early AMD eyes, including both unilateral (AREDS IV) and bilateral (≥AREDS II)) over a minimum of 1 year to specifically investigate the morphological sequence of events preceding the conversion towards late AMD. All patients will be followed by Optical Coherence Tomography (OCT) imaging every 4 months to detect the earliest focal sites of disease progression. As soon as focal areas of change are observed by the Vienna Reading Center (VRC), a targeted follow-up schedule will be triggered to investigate the events at that area of change in a targeted manner.

Description:

We will recruit patients with 1) intermediate AMD in one eye and advanced AMD in the non-study eye or 2) patients with bilateral intermediate AMD (where both eyes will be included). As some participants are symptomless at the stage of intermediate AMD, we will recruit from hospital databases including imaging databases and ophthalmology and optometry practices and engagement with Patient Societies e.g. the Macular Society and patient public involvement meetings.

There will be four clinical sites performing detailed assessments on 50 patients each and, to increase sample size, an additional eight referral sites in the United Kingdom who will each enrol and follow 25 study patients by Spectral Domain Optical Coherence Tomography (SD-OCT) every 4 months. The acquired images from these referral sites will be sent to the Vienna Reading Centre for morphological identification of focal events. If a focal event is detected, participants will then be referred for a detailed, targeted assessment at either the University of Southampton or Moorfields Eye Hospital as detailed below.

After consent, patients will undergo visual function tests (ETDRS visual acuity, microperimetry) and multimodal imaging including fundus photographs, OCT scans, OCT angiography, autofluorescence and adaptive optics imaging. The visual function tests will be repeated annually and the multimodal imaging will be done at 4 monthly intervals for a minimum of 1 year. Blood will be taken within the first year for DNA analysis.

200 patients (main cohort) will undergo dense retinal phenotyping at a minimum of 4 visits.

Medical and smoking history, genotype and body mass index will also be included in the analysis as has been done previously. As well as structural tests, functional tests will be performed at baseline and end of the study using both microperimetry (a type of visual field test to create a "retinal sensitivity map" of the quantity of light perceived in specific parts of the retina) to identify focal changes and low luminance visual acuity to assess global changes. To increase sample size but make the study feasible an additional 200 patients at UK referral sites will undergo 4 monthly OCT and be referred to Southampton / Moorfields for dense phenotyping only if a focal event is detected by OCT.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 429
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 90 Years

Eligibility

Inclusion Criteria:

• Subjects = 55 years with either intermediate AMD (as defined by Ferris et al PMID:

23332590) in both eyes, i.e. large drusen > 125 um and/or any definite hyper- or hypopigmentary abnormalities associated with medium or large drusen; or intermediate AMD as defined above in one eye (study eye) and advanced AMD (geographic atrophy or choroidal neovascularization secondary to AMD) in the other eye.

• Subjects should have media clarity and pupillary dilation for adequate imaging and functional tests.

Exclusion Criteria:

• Co-existent ocular disease, which might affect visual function or retinal morphology

• Established glaucoma in either study eye or fellow eye with evidence of visual field loss or retinal nerve fibre loss (ocular hypertension is not an exclusion criterion unless associated with visual field loss or retinal nerve fibre loss in either eye).

• Cataract sufficient to affect retinal imaging

• Myopia > minus 6 diopters or a history of myopia > minus 6 diopters if patient has had cataract / refractive surgery.

• Major ocular surgery 3 months prior or anticipated within the next 6 months following enrolment.

• Taking drugs known to cause retinal toxicity such as hydroxychloroquine or tamoxifen

• OCT evidence of geographic atrophy (or complete Retinal Pigment Epithelium (RPE) and outer retinal atrophy (cRORA). This is (1) a region of hypertransmission of at least 250 mm in diameter, (2) a zone of attenuation or disruption of the RPE of at least 250 mm in diameter, (3) evidence of overlying photoreceptor degeneration, and (4) absence of scrolled RPE or other signs of an RPE tear.

• OCT evidence of choroidal neovascularization e.g sub-retinal scar tissue, sub-retinal fluid or intra-retinal fluid associated with a pigment epithelial detachment

Related Conditions & MeSH terms

• Age-related Macular Degeneration
• Macular Degeneration

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna
Switzerland	University Hospital Basel	Basel
United Kingdom	University Hospitals Bristol and Weston Nhs Foundation Trust	Bristol
United Kingdom	Frimley Health Nhs Foundation Trust	Frimley	Surrey
United Kingdom	The Princess Alexandra Hospital Nhs Foundation Trust	Harlow	Essex
United Kingdom	Guy'S and St Thomas' Nhs Ft	London
United Kingdom	Moorfields Eye Hospital	London
United Kingdom	St Mary's Hospital, Imperial College Healthcare NHS Trust	London
United Kingdom	St Mary's Hospital	Newport	Isle Of Wight
United Kingdom	John Radcliffe Hospital	Oxford	Oxfordshire
United Kingdom	Salisbury Nhs Foundation Trust	Salisbury	Wiltshire
United Kingdom	University Hospital Southampton	Southampton	Hampshire

Sponsors (7)

Lead Sponsor	Collaborator
University of Southampton	Imperial College London, King's College London, Medical University of Vienna, University College, London, University of Basel, University of Michigan

Countries where clinical trial is conducted

Austria,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sensitivity / specificity of OCT and autofluorescence parameters.	Identified by machine learning (ML) at predicting disease progression defined as focal conversion towards advanced AMD e.g. change in drusen volume, development of new geographic atrophy / choroidal neovascularisation.	3 years
Secondary	Sensitivity / specificity of novel imaging characteristics	For example, Adaptive Optics OCT (AO-OCT), OCT-A, at predicting disease progression; Receiver Operating Characteristic (ROC) curves; time from development of imaging change to development of these end-points; structure-function correlation; structure-genotype correlation; predictive risk models.	3 years

External Links

•   Opt-out of PINNACLE (Retrospective)
•   Protocol and statistical analysis plan PMID: 35614343