The Natural History of the Progression of Atrophy Secondary to Stargardt Disease Type 4: PROM1-Related Macular Dystrophy (ProgStar-4)

August 1, 2018 updated by: Johns Hopkins University

The Natural History of the Progression of Atrophy Secondary to Stargardt Disease Type 4 (STGD4): A Prospective Longitudinal Observational Study of Stargardt Disease Type 4, a PROM1- Related Macular Dystrophy

While a fair amount of clinical data on Stargardt disease type 1 (STGD1) have been published, very little is known about Stargardt disease type 4 (STGD4). The ProgStar 04 study is an important opportunity to leverage the infrastructure, clinical trials sites, methods, and central reading center of the ProgStar program to investigate the progression of STGD4 and will help to establish patient cohorts worldwide for future clinical trials.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

The PROM1 gene codes a protein called Prominin 1 (PROM1; also known as CD133 and AC133), most known for its original use as a human stem cell-specific marker. In the retina, PROM1 is involved in the formation and organization of disks within the outer segment (OS) of the photoreceptors. It is within this particular region that most of the electrochemical signals in response to light are generated (visual cycle-phototransduction). In STGD4, mutations in the PROM1 gene result in a defective isoform of the PROM1 protein that becomes trapped in the myoid region of the photoreceptors and cannot migrate to the OS site where disks are formed. Ultimately, the absence of PROM1 in the OS affects the growth and organization of the disks, which leads to disk malfunction and to vision problems.

Although many advances in genetic science have helped to recognize this variant of STGD, a comprehensive description of the natural history, including the variability in cone and rod dysfunction, of this STGD variant is not available. While there is no known treatment for STGD at this time, the preparation for future therapeutic approaches and for planning clinical trials must include an understanding of the disease itself, its variability, its progression and its correlation with visual loss. Moreover, clinical trials that aim to slow down the progression and/or to restore vision require validated outcome measures to prove treatment efficacy. However, such outcomes have not been established for STGD overall.

In summary, the characterization of STGD4-specific clinical manifestations, progression and prognosis as well as identification of outcome measures for clinical trials are critical to develop new clinical trials for STGD4. Hence, ProgStar 4 is developed as a prospective longitudinal observational study of patients with mutations in the PROM1 gene and a phenotype consistent with STGD.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Contacts and Locations

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

Study Locations

  • Germany
      • Bonn, Germany, 53127
        • Universitäts-Augenklinik Bonn
      • Tuebingen, Germany, 72076
        • Center for Opthalmic Research, University of Tuebingen
  • United Kingdom
      • London, United Kingdom, EC1V 2PD
        • Moorfields Eye Hospital
  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Wilmer Eye Institute
    • Texas
      • Dallas, Texas, United States, 75231
        • Retina Foundation of the Southwest

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

6 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The study shall enroll participants with PROM1 mutations and associated STGD4 phenotype at up to 10 clinical sites.

Description

Inclusion Criteria:

  1. Provide a signed informed consent form and authorization allowing the disclosure and use of protected health information.
  2. The designated primary study eye must have at least one well-demarcated area of atrophy. The lesion size should not exceed the area to be tracked in the OCT mode (20x20 degrees).
  3. Have at least one pathogenic mutation confirmed in the PROM1 gene and a Stargardt phenotype.
  4. The primary study eye must have clear ocular media and adequate pupillary dilation to permit good quality FAF and sd-OCT imaging in the opinion of the investigator.
  5. Be able to cooperate in performing the examinations.
  6. Be willing to undergo ocular examinations once every 6 months for up to 24 months.
  7. Be at least six years old.
  8. Both eyes can be included if inclusion criteria are fulfilled for both eyes.

Exclusion Criteria:

  1. Ocular disease, such as choroidal neovascularization, glaucoma and diabetic retinopathy, in either eye that may confound assessment of the retina morphologically and functionally.
  2. Intraocular surgery in the primary study eye within 90 days prior to baseline visit.
  3. Current or previous participation in an interventional study to treat STGD such as gene therapy or stem cell therapy. Current participation in a drug trial or previous participation in a drug trial within six months before enrollment. The use of oral supplements of vitamins and minerals are permitted although the current use of Vitamin A supplementation shall be documented.
  4. The site Principal Investigator may declare any patient at their site ineligible to participate in the study for a sound medical reason prior to the patient's enrollment into the study.
  5. Any systemic disease with a limited survival prognosis (e.g. cancer, severe/unstable cardiovascular disease).
  6. Any condition that would make adherence to the examination interfere with the patient attending their regular follow-up visits schedule of once every 6 months for up to 24 months difficult or unlikely, e.g. personality disorder, use of major tranquilizers such as Haldol or Phenothiazine, chronic alcoholism, Alzheimer's Disease or drug abuse.
  7. Evidence of significant uncontrolled concomitant diseases such as cardiovascular, neurological, pulmonary, renal, hepatic, endocrine or gastro-intestinal disorders.
  8. Patient is known to have one or more pathogenic mutation(s) in the ABCA4, RDS, or ELOVL4 genes.

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Growth of atrophic lesions as measured by fundus autofluorescence (FAF) imaging
Time Frame: 24 months
24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Growth of atrophic lesions as measured by fundus autofluorescence (FAF) imaging
Time Frame: 12 months
12 months
Rate of retinal thinning and photoreceptor loss as measured by spectral domain optical coherence tomography (sd-OCT)
Time Frame: 12 months
12 months
Rate of retinal thinning and photoreceptor loss as measured by spectral domain optical coherence tomography (sd-OCT)
Time Frame: 24 months
24 months
Loss of retinal sensitivity as measured by microperimetry
Time Frame: 12 months
12 months
Loss of retinal sensitivity as measured by microperimetry
Time Frame: 24 months
24 months
Change in best-corrected visual acuity by using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol
Time Frame: 12 months
12 months
Change in best-corrected visual acuity by using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol
Time Frame: 24 months
24 months
Correlation of all outcome measures with genetic profile
Time Frame: 12 months
12 months
Correlation of all outcome measures with genetic profile
Time Frame: 24 months
24 months

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Johns Hopkins University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
The Shulsky Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 5, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 1, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 7, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 3, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 1, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NA_00092688

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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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