Age-related Macular DegenerationPINNACLENCT04269304
Deciphering AMD by Deep Phenotyping and Machine Learning- Prospective Study - PINNACLE
An observational study of Age-related Macular Degeneration, run by University of Southampton at 12 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 55 to 90 years
- Conditions the study is for
- Age-related Macular Degeneration
- How many people
- 429 participants
- Where
- 12 sitesin 3 countries
- Study dates
- 28 Oct 2019to Jun 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 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).
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
12 sites in 3 countries.
12 sites in 3 countries
United Kingdom10 sites
University Hospitals Bristol and Weston Nhs Foundation Trust
Bristol, BS1 3NU
Frimley Health Nhs Foundation Trust
Frimley, Surrey, GU16 7UJ
The Princess Alexandra Hospital Nhs Foundation Trust
Harlow, Essex, CM20 1QX
Moorfields Eye Hospital
London, EC1V 2PD
Guy'S and St Thomas' Nhs Ft
London, SE1 9RT
St Mary's Hospital, Imperial College Healthcare NHS Trust
London, W2 1NY
St Mary's Hospital
Newport, Isle Of Wight, PO30 5TG
John Radcliffe Hospital
Oxford, Oxfordshire, OX3 9DU
Salisbury Nhs Foundation Trust
Salisbury, Wiltshire, SP2 8BJ
University Hospital Southampton
Southampton, Hampshire, SO16 6YD
About this study
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.
Read the 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
- Medical subject headings
- Macular Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Observational | Intermediate Age-Related Macular Degeneration Patients |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 years
Secondary outcomes (1)
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.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2020
- Study start28 Oct 2019
- Primary completionJun 2025 (estimated)
- Study completionJun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Age-related Macular DegenerationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 429 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southampton
- Sponsor type
- University, hospital or other
- Collaborators
- Imperial College London, University of Basel, Medical University of Vienna, University of Michigan, King's College London, University College, London
- Responsible party
- Sponsor
- Investigators
- Andrew J Lotery, Prof, Principal investigator, University of Southampton
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04269304
- Sponsor's protocol ID
- IRAS - 256931
- Other IDs
- 47270, 210572/Z/18/Z
- Acronym
- PINNACLE
- Status last verified
- Nov 2024
- First submitted
- 11 Feb 2020
- Last updated
- 12 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Requests to access anonymised Individual Participant Data (IPD) can be made on application to the Trial Management Group Data Access Committee.
Publications
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.
PubMed 37624605
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Deciphering AMD by Deep Phenotyping and Machine Learning- Prospective Study - PINNACLE
- ClinicalTrials.gov ID
- NCT04269304
- Acronym / sponsor ID
- PINNACLE / IRAS - 256931
- Conditions
- Age-related Macular Degeneration
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 429 participants (actual)
- Lead sponsor
- University of SouthamptonUniversity, hospital or other
- Collaborators
- Imperial College London, University of Basel, Medical University of Vienna, University of Michigan, King's College London, University College, London
- Study start
- 28 Oct 2019 (actual)
- Primary completion
- Jun 2025 (estimated)
- Study completion
- Jun 2025 (estimated)
- First posted
- 13 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Observational | – | –Intermediate Age-Related Macular Degeneration Patients |
Who may qualify
- Ages
- 55 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 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).
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Sensitivity / specificity of OCT and autofluorescence parameters.
Time frame: 3 years
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.
1 secondary outcome
Sensitivity / specificity of novel imaging characteristics
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2024.
- Derived from this study: PubMed 37624605Anders 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.
- Opt-out of PINNACLE (Retrospective)Link provided by the sponsor.
- Protocol and statistical analysis plan PMID: 35614343Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Requests to access anonymised Individual Participant Data (IPD) can be made on application to the Trial Management Group Data Access Committee.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew J Lotery, Prof principal investigator
University of Southampton
12 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Age-related Macular Degeneration, run by University of Southampton at 12 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United Kingdom, Austria, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sensitivity / specificity of OCT and autofluorescence parameters. (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04269304, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2024.