Clinical Trial: Erythropoietic Protoporphyrias: Studies of the Natural History, Genotype-Phenotype Correlations, and Psychosocial Impact

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Erythropoietic Protoporphyrias: Studies of the Natural History, Genotype-Phenotype Correlations, and Psychosocial Impact

Brief Summary: The initial objective of this protocol is to assemble a well-documented group of patients with confirmed diagnoses of the erythropoietic protoporphyrias, including autosomal recessive Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP) for clinical, biochemical, and genetic studies. The long-term objectives are (1) to conduct a longitudinal investigation of the natural history, complications, and therapeutic outcomes in people with erythropoietic protoporphyria, (2) to systematically investigate the psychological effects of the erythropoietic protoporphyrias on children and adults, and (3) to investigate the correlation between the identified genotypes and the resulting clinical presentation, also determining the possible interaction of other genetic markers.

Detailed Summary:

The porphyrias are a group of rare metabolic diseases that may present in childhood or adult life and are due to deficiencies of enzymes in the heme biosynthetic pathway. The most common manifestations are related to accumulation of intermediates in the pathway and usually occur as acute neurological attacks (as in the acute or hepatic porphyrias), or cutaneous photosensitivity (as in the cutaneous porphyrias, including the erythropoietic protoporphyrias). Multiple mutations have been identified in each of the porphyrias [Anderson, 2001]. The risk of disability or death from these disorders is significant, in part because diagnosis is often delayed due to lack of adoption of diagnostic testing in clinical practice. Moreover, the natural history of these disorders is not well described and it is not known what determines differences in outcomes. New therapies are needed. For existing therapies, high-quality evidence on short and long term efficacy and safety is generally lacking [Sood 2008]. Therefore, the purpose of this study of a large group of patients with EPP and XLP is to provide a better understanding of the natural history of these disorders, as affected by available therapies, and to aid in developing new forms of treatment. Much of the data collected on subjects as participants in the Longitudinal Study of the Porphyrias will be accessed for this study specific to the investigation of the erythropoietic protoporphyrias. To maximize the information that can be informative in our objectives, additional data will be collected, including additional biochemical findings and EPP-specific psychosocial parameters.

The Office of Rare Diseases (ORD) of the National Institutes of Health (NIH) established a Rare Diseases Clinical Research Network (RDCRN) in collaboration with other NIH Institutes and currently has funded 19 rare diseases clinical research consortia and one
Sponsor: Icahn School of Medicine at Mount Sinai

Current Primary Outcome: Clinical Analysis [ Time Frame: baseline, then annually, up to 3 years ]

To develop disease severity scores to describe the combined frequency and severity of disease manifestations, utilizing linear mixed effects models & stratification by age of onset.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Laboratory Analysis [ Time Frame: baseline, then annually, up to 3 years ]
    To evaluate porphyrin and porphyrin precursor levels alone or by genotype and porphyria subtype
  • Relationship between disease severity and biomarkers [ Time Frame: baseline, then annually, up to 3 years ]
    To develop longitudinal models that relate, for example, porphyrin and porphyrin precursor levels alone or in concert with age, genotype and other features to the disease manifestation frequency.


Original Secondary Outcome: Same as current

Information By: Icahn School of Medicine at Mount Sinai

Dates:
Date Received: September 14, 2012
Date Started: July 2012
Date Completion: December 2019
Last Updated: August 3, 2016
Last Verified: August 2016