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

NCT ID: NCT04269304

Last Updated: 2024-11-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 429 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-10-28
• Study Completion Date: 2025-06-30

Brief 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.

Detailed 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.

Conditions

Age-related Macular Degeneration

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Observational

Intermediate Age-Related Macular Degeneration Patients

No interventions assigned to this group

Eligibility Criteria

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

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Imperial College London

OTHER

Sponsor Role: collaborator

University of Basel

OTHER

Sponsor Role: collaborator

Medical University of Vienna

OTHER

Sponsor Role: collaborator

University of Michigan

OTHER

Sponsor Role: collaborator

King's College London

OTHER

Sponsor Role: collaborator

University College, London

OTHER

Sponsor Role: collaborator

University of Southampton

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrew J Lotery, Prof

Role: PRINCIPAL_INVESTIGATOR

University of Southampton

Locations

Medical University of Vienna

Vienna, , Austria

University Hospital Basel

Basel, , Switzerland

The Princess Alexandra Hospital Nhs Foundation Trust

Harlow, Essex, United Kingdom

University Hospital Southampton

Southampton, Hampshire, United Kingdom

St Mary's Hospital

Newport, Isle Of Wight, United Kingdom

John Radcliffe Hospital

Oxford, Oxfordshire, United Kingdom

Frimley Health Nhs Foundation Trust

Frimley, Surrey, United Kingdom

Salisbury Nhs Foundation Trust

Salisbury, Wiltshire, United Kingdom

University Hospitals Bristol and Weston Nhs Foundation Trust

Bristol, , United Kingdom

Moorfields Eye Hospital

London, , United Kingdom

Guy'S and St Thomas' Nhs Ft

London, , United Kingdom

St Mary's Hospital, Imperial College Healthcare NHS Trust

London, , United Kingdom

Countries

Austria; Switzerland; United Kingdom

References

Anders P, Traber GL, Pfau M, Riedl S, Hagag AM, Camenzind H, Mai J, Kaye R, Bogunovic H, Fritsche LG, Rueckert D, Schmidt-Erfurth U, Sivaprasad S, Lotery AJ, Scholl HPN. Comparison of Novel Volumetric Microperimetry Metrics in Intermediate Age-Related Macular Degeneration: PINNACLE Study Report 3. Transl Vis Sci Technol. 2023 Aug 1;12(8):21. doi: 10.1167/tvst.12.8.21.

Reference Type: DERIVED

PMID: 37624605 (View on PubMed)

Related Links

https://clinicalresearch.uhs.nhs.uk/take-part

Opt-out of PINNACLE (Retrospective)

https://pubmed.ncbi.nlm.nih.gov/35614343/

Protocol and statistical analysis plan PMID: 35614343

Other Identifiers

47270

Identifier Type: OTHER

Identifier Source: secondary_id

210572/Z/18/Z

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

IRAS - 256931

Identifier Type: -

Identifier Source: org_study_id