NCT03349801

Brief Summary

Development of novel clinical endpoints for interventional clinical trials with a regulatory and patient access intention in patients with intermediate age-related macular degeneration (AMD) - MACUSTAR

Trial Health

62
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
718

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Mar 2018

Longer than P75 for all trials

Geographic Reach
7 countries

20 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 10, 2017

Completed
12 days until next milestone

First Posted

Study publicly available on registry

November 22, 2017

Completed
4 months until next milestone

Study Start

First participant enrolled

March 26, 2018

Completed
7.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 28, 2026

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 28, 2026

Completed
Last Updated

January 16, 2025

Status Verified

January 1, 2025

Enrollment Period

7.9 years

First QC Date

November 10, 2017

Last Update Submit

January 13, 2025

Conditions

Age Related Macular Degeneration (AMD)

Keywords

iAMDbiomarkerclinical endpoint

Outcome Measures

Primary Outcomes (30)

  • Mean change from baseline in best corrected visual acuity (BCVA) using an early treatment diabetic retinopathy study (ETDRS) chart

    standard parameter, tested for comparison (reference variable)

    3 years from baseline

  • Mean change from baseline in scotopic and mesopic microperimetry sensitivity

    3 years from baseline

  • Mean change from baseline in low luminance visual acuity (LLVA)

    3 years from baseline

  • Mean change from baseline in vanishing optotypes visual acuity (VA)

    3 years from baseline

  • Mean change from baseline in low luminance deficit (LLD)

    LLD = BCVA-LLVA

    3 years from baseline

  • Mean change from baseline in absolute rod threshold of the dark adaptation test

    3 years from baseline

  • Mean change from baseline in rod intercept time of the dark adaptation test

    3 years from baseline

  • Proportion of subjects with progression in dark adaptation deficit beyond coefficient of repeatability structural

    3 years from baseline

  • Mean change from baseline in the cube root of drusen volume by spectral-domain optical coherence tomography (SD-OCT)

    3 years from baseline

  • Mean change from baseline in retinal thickness by spectral-domain optical coherence tomography (SD-OCT)

    3 years from baseline

  • Focal pigmentary changes captured by colour fundus photography (CFP)

    3 years from baseline

  • Presence of refractile deposits

    3 years from baseline

  • Presence of intraretinal cystoid spaces

    3 years from baseline

  • Presence of localized retinal pigment epithelium (RPE) hypertransmission

    3 years from baseline

  • Presence of localized disruption of ellipsoid zone

    3 years from baseline

  • Presence of localized subsidence of the outer plexiform layer and the inner nuclear layer

    3 years from baseline

  • Presence of hyporeflective wedge-shaped bands

    3 years from baseline

  • Presence of reticular drusen/subretinal drusenoid deposits and associated local changes as determined by multimodal imaging

    3 years from baseline

  • Changes in localized fundus autofluorescence signal alterations

    3 years from baseline

  • Proportion of subjects with reduction in drusen volume

    3 years from baseline

  • Proportion of subjects with study eye that progressed to geogrphic atrophy (GA) and/or neovascular age-related macular degeneration (nAMD)

    3 years from baseline

  • Proportion of subjects with conversions to late AMD detected with fluorescein angiography (FA) that could be detected with OCT-A (at equipped sites)

    3 years from baseline

  • Presence of quiescent choroidal neovascularisation (CNV) as assessed by optical coherence tomography angiography (OCT-A) (at equipped sites)

    3 years from baseline

  • OCT-A findings (at equipped sites)

    3 years from baseline

  • Mean change from baseline in patient-reported low luminance visual functioning, as measured by the vision impairment in low luminance (VILL) questionnaire, including the domains of reading & accessing information

    3 years from baseline

  • Mean change from baseline in patient-reported low luminance visual functioning, as measured by the VILL questionnaire, including the domains of Orientation & mobility (incl. driving)

    3 years from baseline

  • Mean change from baseline in patient-reported low luminance visual functioning, as measured by the VILL questionnaire, including the domains of safety

    3 years from baseline

  • Mean change from baseline in patient-reported low luminance visual functioning, as measured by the VILL questionnaire, including the domains of socio-emotional well-being

    3 years from baseline

  • Change in utility index from baseline as measure by the patient-reported outcome measure (PROM) utility index

    3 years from baseline

  • Mean change from baseline in patient-reported health status and utility using the EQ-5D-5L questionnaire (EuroQol Group)

    3 years from baseline

Study Arms (4)

no AMD

No interventions

Other: No intervention

early AMD

No interventions.

Other: No intervention

intermediate AMD

No interventions.

Other: No intervention

late AMD

No interventions.

Other: No intervention

Interventions

No interventionOTHER

According to clinical practice.

early AMDintermediate AMDlate AMDno AMD

Eligibility Criteria

Age55 Years - 85 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

The study will include subjects with no AMD or normal aging changes and subjects with AMD classified in accordance with the international Beckman Classification. A total of 750 subjects will be recruited: * 300 subjects will participate in the Cross-sectional part: * 50 with normal aging changes, no AMD * 50 with early AMD, * 50 with late AMD * 150 with iAMD * 650 subjects will participate in the longitudinal part: * 600 iAMD * 50 early AMD

You may qualify if:

  • Male and female subjects.
  • Aged 55 - 85 years at baseline.
  • Able and willing to provide written informed consent and to comply with the study protocol visits and assessments.
  • Intermediate AMD
  • Study eye must have iAMD and,
  • The fellow eye must have iAMD and/or, in addition, extrafoveal GA (no atrophy within the central ETDRS subfield), maximum total GA size is 1.25 mm2.
  • ETDRS letter chart BCVA in the study eye not worse than 72 letters (approximately 20/40 Snellen VA equivalent).
  • Late AMD
  • Subjects with bilateral GA, bilateral nAMD or nAMD in one eye and GA in the other.
  • BCVA between 20/80 and 20/200 in study eye.
  • Early AMD
  • Subjects with medium drusen \> 63μm and ≤ 125μm and no AMD pigmentary abnormalities in both eyes and not signs of intermediate or late AMD.
  • No AMD
  • No signs of early, intermediate or late AMD in both eyes.

You may not qualify if:

  • Media opacity or eye movement disorder (nystagmus) that interferes with retinal imaging data quality in the opinion of the investigator.
  • Severe ptosis, extraocular motility restriction or head tremor preventing adequate fundus visualization in the opinion of the investigator.
  • Any signs of nAMD or GA (does not apply to the late AMD group).
  • Any concurrent intraocular condition in the study eye (e. g. glaucoma or cataract) that, in the opinion of the investigator would either require surgical intervention during the study to prevent or treat visual loss that might result from that condition or affect interpretation of study results.
  • Severe non-proliferative diabetic retinopathy, or proliferative diabetic retinopathy.
  • Any diabetic macular edema or macular disease
  • Ocular disorders in the study eye (i. e., pre-retinal membrane) at the time of enrolment that may confound interpretation of study results and compromise visual acuity.
  • Diagnosis of uncontrolled glaucoma with intraocular pressure of \>30 mmHg (despite current pharmacological or non-pharmacological treatment).
  • Known systemic illness which in the opinion of the investigator will prevent from actively participating in the study.
  • Concomitant treatment for AMD in either eye (concomitant use of vitamins/supplements is not excluded; does not apply to the late AMD group).
  • Any periocular or intravitreal injections (IVT) in either eye (does not apply to the late AMD group).
  • Participation in any other interventional trial.
  • Obvious retinal changes due to causes other than AMD (e.g. evidenced by an existing diagnosis of monogenetic macular dystrophies, Stargardt disease, cone rod dystrophy, or toxic maculopathies).
  • Any history of allergies to fluorescein.
  • Intermediate AMD
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (20)

Righospitalet Copenhagen

Copenhagen, Denmark

Location

Centre Hospitalier Intercommunal de Creteil

Créteil, France

Location

Centre d'Investigation Clinique Centre National d'Ophtalmologie des Quinze-Vingts

Paris, France

Location

University Hospital Bonn

Bonn, Germany

Location

University Hospital Cologne

Cologne, Germany

Location

Department of Ophthalmology, University of Freiburg

Freiburg im Breisgau, Germany

Location

University Eye Hospital Munich

Munich, Germany

Location

St. Franziskus Hospital

Münster, Germany

Location

Universtiy Hospital Tuebingen

Tübingen, Germany

Location

University Eye Hospital Ulm

Ulm, Germany

Location

Luigi Sacco Hospital

Milan, Italy

Location

Ospedale San Raffaele

Milan, Italy

Location

G.B.Bietti Eye Foundation

Rome, Italy

Location

Radboud University Medical Centre

Leiden, Netherlands

Location

Radboud University Medical Centre

Nijmegen, Netherlands

Location

Centre for Clinical Trials, AIBILI

Coimbra, Portugal

Location

Centro Hospitalar de São João, E.P.E.

Porto, Portugal

Location

Queen's University Belfast

Belfast, United Kingdom

Location

Gloucestershire Hospitals NHS Foundation Trust

Gloucester, United Kingdom

Location

Moorfields Eye Hospital

London, United Kingdom

Location

Related Publications (8)

  • Rowen D, Carlton J, McDool E, Holz FG, Zakaria N, Terheyden JH, Finger RP; MACUSTAR Consortium. Psychometric Performance of a New Condition-Specific Preference-Weighted Measure, Vision Impairment in Low Luminance-Utility Index, and EQ-5D-5L in Patients With Age-Related Macular Degeneration: A MACUSTAR Study Report. Value Health. 2025 Jul;28(7):1082-1090. doi: 10.1016/j.jval.2025.04.2155. Epub 2025 Apr 26.

    PMID: 40294859DERIVED

  • Terheyden JH, Dunbar HMP, Schmitz-Valckenberg S, Behning C, Martinho C, Luhmann UFO, Sassmannshausen M, Luning A, Miliu A, Aires ID, Basile PG, Batuca J, Schmid M, Moll KP, Zakaria N, Tufail A, Binns A, Crabb DP, Leal S, Finger RP, Holz FG; MACUSTAR consortium. Validating candidate endpoints for intermediate age-related macular degeneration trials in a multi-centre setting-lessons from the MACUSTAR study. Eye (Lond). 2025 Apr;39(6):1031-1039. doi: 10.1038/s41433-024-03568-2. Epub 2025 Feb 5.

    PMID: 39910281DERIVED

  • Rowen D, Carlton J, Terheyden JH, Finger RP, Wickramasekera N, Brazier J; MACUSTAR Consortium. Development and Valuation of a Preference-Weighted Measure in Age-Related Macular Degeneration From the Vision Impairment in Low Luminance Questionnaire: A MACUSTAR Report. Value Health. 2024 May;27(5):642-654. doi: 10.1016/j.jval.2024.02.001. Epub 2024 Feb 17.

    PMID: 38369283DERIVED

  • Sassmannshausen M, Behning C, Weinz J, Goerdt L, Terheyden JH, Chang P, Schmid M, Poor SH, Zakaria N, Finger RP, Holz FG, Pfau M, Schmitz-Valckenberg S, Thiele S; MACUSTAR Consortium Members. Characteristics and Spatial Distribution of Structural Features in Age-Related Macular Degeneration: A MACUSTAR Study Report. Ophthalmol Retina. 2023 May;7(5):420-430. doi: 10.1016/j.oret.2022.12.007. Epub 2022 Dec 20.

    PMID: 36563964DERIVED

  • Garzone D, Terheyden JH, Morelle O, Wintergerst MWM, Sassmannshausen M, Schmitz-Valckenberg S, Pfau M, Thiele S, Poor S, Leal S, Holz FG, Finger RP; MACUSTAR Consortium. Comparability of automated drusen volume measurements in age-related macular degeneration: a MACUSTAR study report. Sci Rep. 2022 Dec 19;12(1):21911. doi: 10.1038/s41598-022-26223-w.

    PMID: 36535990DERIVED

  • Terheyden JH, Pondorfer SG, Behning C, Berger M, Carlton J, Rowen D, Bouchet C, Poor S, Luhmann UFO, Leal S, Holz FG, Butt T, Brazier JE, Finger RP; MACUSTAR consortium. Disease-specific assessment of Vision Impairment in Low Luminance in age-related macular degeneration - a MACUSTAR study report. Br J Ophthalmol. 2023 Aug;107(8):1144-1150. doi: 10.1136/bjophthalmol-2021-320848. Epub 2022 Mar 30.

    PMID: 35354561DERIVED

  • Terheyden JH, Behning C, Luning A, Wintergerst L, Basile PG, Tavares D, Melicio BA, Leal S, Weissgerber G, Luhmann UFO, Crabb DP, Tufail A, Hoyng C, Berger M, Schmid M, Silva R, Martinho CV, Cunha-Vaz J, Holz FG, Finger RP; MACUSTAR consortium. Challenges, facilitators and barriers to screening study participants in early disease stages-experience from the MACUSTAR study. BMC Med Res Methodol. 2021 Mar 17;21(1):54. doi: 10.1186/s12874-021-01243-8.

    PMID: 33731014DERIVED

  • Terheyden JH, Holz FG, Schmitz-Valckenberg S, Luning A, Schmid M, Rubin GS, Dunbar H, Tufail A, Crabb DP, Binns A, Sanchez CI, Hoyng C, Margaron P, Zakaria N, Durbin M, Luhmann U, Zamiri P, Cunha-Vaz J, Martinho C, Leal S, Finger RP; MACUSTAR consortium. Clinical study protocol for a low-interventional study in intermediate age-related macular degeneration developing novel clinical endpoints for interventional clinical trials with a regulatory and patient access intention-MACUSTAR. Trials. 2020 Jul 18;21(1):659. doi: 10.1186/s13063-020-04595-6.

    PMID: 32682441DERIVED

Related Links

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples are collected in the study for two purposes: biobanking and genetic analysis. Detailed instructions on processing and storage of blood samples are provided in a specific manual that will be provided to the clinical sites. Blood samples are stored in a pseudonimysed form.

MeSH Terms

Conditions

Macular Degeneration

Condition Hierarchy (Ancestors)

Retinal DegenerationRetinal DiseasesEye Diseases

Study Officials

  • Frank Holz, Prof. Dr. med.

    University Hospital, Bonn

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Prof. Dr. med.

Study Record Dates

First Submitted

November 10, 2017

First Posted

November 22, 2017

Study Start

March 26, 2018

Primary Completion

February 28, 2026

Study Completion

February 28, 2026

Last Updated

January 16, 2025

Record last verified: 2025-01

Data Sharing

IPD Sharing
Will not share

Locations

NL(2)PT(2)DE(7)GB(3)IT(3)DK(1)FR(2)