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

Stargardt Disease Clinical Trial

Official title: 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

Status Completed

Clinical Trial Summary

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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Atrophy
• Macular Degeneration
• Stargardt Disease

• NCT number: NCT02410122
• Study type: Observational
• Source: Johns Hopkins University
• Status: Completed
• Start date: December 2014
• Completion date: March 2018