Deciphering AMD by Deep Phenotyping and Machine Learning- Prospective Study - SUMMIT (Part 2)

• Conditions: Age-Related Macular Degeneration

• Registration Number: NCT06682455
• Lead Sponsor: University of Southampton

Brief Summary

We will conduct a prospective, non-interventional roll-over extension of the PINNACLE study (Deciphering AMD by deep phenotyping and machine learning). This will include up to 300 intermediate AMD participants (= approximately 450 untreated intermediate AMD eyes, including both unilateral (AREDS IV) and bilateral (≥AREDS II)). As per the PINNACLE study, SUMMIT study participants will continue to be followed using OCT imaging every 4 months for a further 2-years, to specifically investigate the morphological sequence of events preceding the conversion towards late AMD. Across both studies combined, we will be able to detect the earliest focal sites of disease progression over a total 5-year follow-up.

Detailed Description

Participants who have taken part in the PINNACLE study and have progressed to the final visit (i.e. have not made the decision to withdraw or met any withdrawal criteria prior to completing month 36/visit 10), within 12 months of enrolment to SUMMIT will be considered for this cohort.

We will recruit patients with a continued diagnosis of 1) intermediate AMD in the study eye and advanced AMD in the non-study eye or 2) patients with bilateral intermediate AMD (where both eyes will be included).

As within PINNACLE, there will be four clinical sites performing detailed assessments on their recruited patients, and an additional eight referral sites in the United Kingdom who will follow patients by Spectral Domain Optical Coherence Tomography (SD-OCT) every 4 months. The acquired images from all sites will be sent to the Vienna Reading Centre for review.

After consent, study assessments including both structural and functional visual testing and imaging procedures, and the collection of medical and medication data will be performed at 4-monthly intervals across a maximum 2-year period. Participants will attend a maximum of 6 visits, 2 of which (M48 and M60), will be classified as 'annual' visits, where enhanced imaging and testing will take place to further identify and assess focal and global changes.

Demographic data collected as part of the PINNACLE study baseline procedures, including birth year, smoking history and body mass index data will not be re-collected as part of the SUMMIT study. The information previously collected will however be included within the SUMMIT analysis, as has also been considered previously. The data extracted from the genotyping samples within the PINNACLE study will also be included in the SUMMIT final analysis, but no additional samples or research on existing samples will be performed under the SUMMIT study protocol.

Study Timeline

• Study Start: 2024-06-12
• Status Verified: 2024-11
• Study First Submitted: 2024-11-07
• Study First Submitted QC: 2024-11-07
• Last Update Submitted: 2024-11-07
• Study First Posted: 2024-11-11
• Last Update Posted: 2024-11-11
• Primary Completion: 2027-06-30
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

1. Have taken part in the PINNACLE study and progressed to/completed the final M36/V10 study visit.

2. Have not been considered 'withdrawn' (either by 'opt-out', or any reason that would deem them ineligible, e.g. disease progression) from the PINNACLE study at any timepoint.

3. Have a period of no longer than 12 months between their final M36/V10 PINNACLE study visit and the first SUMMIT study visit (if M36/V10 was missed, the participant will still be eligible if M32/V9 completion date is within 12 months of enrolment).

4. Continued diagnosis of intermediate AMD (as defined by Ferris et al PMID: 23332590) in both eyes (i.e. large drusen > 125 µm 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 (GA or MNV secondary to AMD) in the other eye.

   Participants enrolled with both eyes (OU) on the PINNACLE study, will still be eligible to enrol under OD/OS only, should one eye have been withdrawn prior to completing PINNACLE, or considered no longer eligible during enrolment on SUMMIT.

5. Have media clarity and pupillary dilation for adequate imaging and functional tests.

6. Deemed able to meet the physical demands of attending 4-monthly appointments and undergo the examinations as listed in section 7.3, for the study duration (maximum 2 years).

Exclusion Criteria

1. Co-existent ocular disease, which might affect visual function or retinal morphology.
2. 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).
3. Cataract sufficient to affect retinal imaging.
4. Myopia > minus 6 diopters or a history of myopia > minus 6 diopters if patient has had cataract/refractive surgery.
5. Major ocular surgery (e.g. corneal transplant, vitreo-retinal surgery) 3 months prior or anticipated within the next 6 months following enrolment (not including cataract surgery).
6. Taking drugs known to cause retinal toxicity, such as hydroxychloroquine or tamoxifen.
7. OCT evidence of MNV (e.g sub-retinal scar tissue, sub-retinal fluid or intra-retinal fluid associated with a pigment epithelial detachment).
8. Participants who have completed the PINNACLE study >12 months prior to their enrolment on SUMMIT.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Sensitivity / specificity of OCT biomarkers	2 years	Sensitivity / specificity of OCT biomarkers identified in the retrospective branch of our study at predicting disease progression towards advanced AMD i.e. development of early onset neurosensory atrophy or choroidal neovascularisation.

Secondary Outcome Measures

Name	Time	Method
Sensitivity / specificity of novel imaging characteristics	2 years	Sensitivity / specificity of novel imaging characteristics e.g. fundus autofluorescence, AO-OCT, OCT-A at predicting disease progression; ROC curves; time from development of imaging change to development of these end-points; structure-function correlation; structure-genotype correlation; predictive risk models.

Trial Locations

Locations (8)

Medical University of Vienna; 🇦🇹 Vienna, Austria

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

Moorfields Eye Hospital; 🇬🇧 London, United Kingdom