FECD-TRACE: Fuchs' Endothelial Corneal Dystrophy TRAjectory and Correlation With Genotype in the United Kingdom (FECD-TRACE)

March 11, 2025 updated by: University College, London

Investigating Genetic Causes and Molecular Mechanisms Responsible for Inherited Corneal Disease

FECD-TRACE is an integral component of a large research program dedicated to Fuchs Endothelial Corneal Dystrophy (FECD) in the United Kingdom. This longitudinal, observational study aims to comprehensively characterize a cohort of younger research participants who have a genetic predisposition to developing FECD. By utilizing advanced anterior segment imaging techniques, the study will monitor these individuals over a span of several years, capturing phenotypic changes that reflect the progression of the disease. Concurrently, genetic biomarkers will be examined to establish correlations with the observed phenotypic changes. The primary objective of FECD-TRACE is to enhance our understanding of the intricate genetic mechanisms underlying FECD and establish connections between these genetic findings and clinical outcomes. Ultimately, this research strives to facilitate the development of personalized care approaches for individuals affected by FECD.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

FECD is the most prevalent repeat expansion disease in humans. Clinical anticipation and intergenerational expansion of disease-associated repeats are features of other repeat expansion diseases, but this area has not been comprehensively addressed in FECD. Due to its insidious onset and slow disease progression, early diagnosis of FECD in pre-symptomatic patients is challenging.

To gain insights into the variable penetrance of FECD and to identify early signs of the disease in genetically predisposed but asymptomatic individuals (i.e., a pre-symptomatic cohort), we aim to recruit biological relatives of FECD patients receiving care at study sites, as well as individuals with early-stage disease. By combining genotyping and clinical phenotyping, we seek to elucidate the underlying factors influencing disease manifestation.

Our deep phenotyping approach encompasses an array of advanced imaging techniques such as visual acuity assessment, contrast sensitivity evaluation, slit-lamp photography, specular microscopy, Scheimpflug tomography, and anterior segment optical coherence tomography. These cutting-edge modalities enable the detection of subclinical corneal edema by revealing subtle changes in corneal shape, volume, and reflectivity at a high resolution.

The imaging data obtained from participants will undergo meticulous quantitative analysis, allowing for the classification of anterior segment features and extraction of image-derived phenotypes. To capture the dynamic nature of FECD, eligible participants will be invited for follow-up examinations, facilitating a longitudinal assessment of disease progression.

Study Type

Observational

Enrollment (Estimated)

500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United Kingdom
      • London, United Kingdom, EC1V 9EL
        • Recruiting
        • University College London
        • Contact:
          • Siyin Liu
          • Phone Number: +4420 7608 6800
        • Principal Investigator:
          • Siyin Liu, MBChB

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Participants meeting the recruitment criteria across multiple sites will be enrolled

Description

Inclusion Criteria:

  • Willing and able to provide informed consent for participation in the study
  • Willing to attend scheduled study visits and undergo a clinical examination
  • Willing to donate blood/saliva samples
  • Fulfil the abovementioned cohort criteria

Exclusion Criteria:

  • Presence of a secondary cause for corneal endothelial dysfunction or oedema
  • Presence of clinically evident corneal oedema
  • History of concurrent corneal diseases
  • History of corneal surgeries, including corneal transplantation
  • Cognitive impairment or inability to provide informed consent for participation in the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Pre-symptomatic FECD cohort
  1. Have at least one biological first-degree relative with a confirmed diagnosis of FECD AND have TCF4 gene CTG18.1 expansion ≥ 50 repeats OR
  2. Confirmed diagnosis of FECD by a qualified ophthalmologist but does not have clinically evident corneal oedema
Diagnostic test: Clinical phenotyping
  • Visual acuity assessment
  • Contrast sensitivity evaluation
  • Slit-lamp photography
  • Specular microscopy
  • Scheimpflug tomography
  • Anterior segment optical coherence tomography
  • In vivo confocal microscopy
  • Spatio-temporal optical coherence tomography
Genetic: CTG18.1 Expansion Status Genotyping

Genotyping for trinucleotide repeat in the TCF4 gene (CTG18.1) and other genetic biomarkers using blood or saliva derived genomic DNA. This includes:

  • Short tandem repeat - PCR
  • Triplet-repeat primed - PCR
  • Genome-wide single nucleotide polymorphism genotyping
  • Ultra-deep locus-specific next-generation sequencing
Control cohort
  1. Have no known family history nor clinical features of FECD OR
  2. Have known family history of FECD but have been tested for the TCF4 gene CTG18.1 expansion and are not at genetic risk for FECD (CTG < 50 repeats).
Diagnostic test: Clinical phenotyping
  • Visual acuity assessment
  • Contrast sensitivity evaluation
  • Slit-lamp photography
  • Specular microscopy
  • Scheimpflug tomography
  • Anterior segment optical coherence tomography
  • In vivo confocal microscopy
  • Spatio-temporal optical coherence tomography
Genetic: CTG18.1 Expansion Status Genotyping

Genotyping for trinucleotide repeat in the TCF4 gene (CTG18.1) and other genetic biomarkers using blood or saliva derived genomic DNA. This includes:

  • Short tandem repeat - PCR
  • Triplet-repeat primed - PCR
  • Genome-wide single nucleotide polymorphism genotyping
  • Ultra-deep locus-specific next-generation sequencing

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endothelial cell density measurement (cells/mm2)
Time Frame: Baseline
Specular Microscopy - Endothelial cell density.
Baseline
CTG18.1 allele length (in number)
Time Frame: Baseline
Polymerase Chain Reaction (PCR) will be performed from DNA (blood sample)
Baseline
Detection of guttata (cells/mm2)
Time Frame: Baseline
In Vivo Confocal Microscopy (IVCM) - Detection of guttata
Baseline
Corneal thickness (in micrometers)
Time Frame: Baseline
Anterior Segment Optical Coherence Tomography (AS-OCT) - Corneal thickness
Baseline
Documentation of early corneal guttata development (Binary)
Time Frame: Baseline
Slit-Lamp Photography - Documentation of early corneal guttata development.
Baseline
Best-corrected visual acuity in LogMAR scale
Time Frame: Baseline
Visual acuity measured by LogMAR chart
Baseline
Corneal nerve density (nerves/mm2)
Time Frame: Baseline
In Vivo Confocal Microscopy (IVCM) - Detection of nerves
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University College, London

Investigators

  • Principal Investigator: Alice Davidson, PhD, University College, London

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2024

Primary Completion (Estimated)

February 1, 2026

Study Completion (Estimated)

February 1, 2027

Study Registration Dates

First Submitted

February 28, 2025

First Submitted That Met QC Criteria

March 11, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 11, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 145682

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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