Clinical Trial: Longitudinal Study of the Porphyrias

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

Official Title: Longitudinal Study of the Porphyrias

Brief Summary: The objective of this protocol is to conduct a longitudinal multidisciplinary investigation of the human porphyrias including the natural history, morbidity, pregnancy outcomes, and mortality in people with these disorders.

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, or cutaneous photosensitivity. Multiple mutations have been identified in each of the porphyrias. 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. Therefore, the purpose of this long-term follow-up study of a large group of patients with the various porphyrias 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.

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 Data Management and Coordinating Center. The Porphyrias Consortium was created as part of the RDCRN, to study the human porphyrias. The Porphyrias Consortium is a consortium of the academic institutions listed in the participating institutions table. All Centers in the Porphyrias Consortium are participating in the Longitudinal Study of the Porphyrias. Additional centers may be added if funding is available.

The initial objective of this protocol is to
Sponsor: Icahn School of Medicine at Mount Sinai

Current Primary Outcome:

• clinical analysis [ Time Frame: baseline ]
  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.
• Laboratory analysis [ Time Frame: baseline ]
  To evaluate porphyrin and porphyrin precursor levels alone or by genotype and porphyria subtype

Original Primary Outcome:

• clinical analysis [ Time Frame: baseline ]
  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.
• clinical analysis [ Time Frame: year 1 ]
  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.
• clinical analysis [ Time Frame: year 2 ]
  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.
• clinical analysis [ Time Frame: year 3 ]
  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.
• clinical analysis [ Time Frame: year 4 ]
  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.
• Laboratory analysis [ Time Frame: baseline ]
  To evaluate porphyrin and porphyrin precursor levels alone or by genotype and porphyria subtype
• Laboratory analysis [&nb
  
  

  Current Secondary Outcome:

  • Relationship between disease severity and biomarkers [ Time Frame: baseline ]
    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.
  • Effectiveness and tolerability of currently used and new therapies for the human porphyrias [ Time Frame: baseline ]
    Qualitative evaluation, using self-reporting questionnaires and clinical findings, and quantitative evaluation, using laboratory measures of organ function and porphyrin levels, to evaluate the effectiveness of therapies.
  
  
  

  Original Secondary Outcome:

  • Relationship between disease severity and biomarkers [ Time Frame: baseline ]
    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.
  • Relationship between disease severity and biomarkers [ Time Frame: year 1 ]
    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.
  • Relationship between disease severity and biomarkers [ Time Frame: year 2 ]
    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.
  • Relationship between disease severity and biomarkers [ Time Frame: year 3 ]
    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.
  • Relationship between disease severity and biomarkers [ Time Frame: year 4 ]
    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.
  • Effectiveness and tolerability of currently used and new therapies for the human porphyrias [ Time Frame: baseline ]
    Qualitative evaluation, using self-reporting questionnaires and clinical findings, and quantitative evaluation, using laboratory measures of organ function and porphyrin levels, to evaluate the effectiveness of therapies.
  • Effectiveness and tolerability of currently used and new therapies for the human porphyrias [ Time Frame: year 1 ]
    Qualitative evaluation, using self-reporting questionnaires and clinical findings, and quantitative evaluation, using laboratory measures of organ function and porphyrin levels, to evaluate the effectiveness of therapies.
  • Effectiveness and tolerability of currently used and new therapies for the human porphyrias [ Time Frame: year 2 ]
    Qualitative evaluation, using self-reporting questionnaires and clinical findings, and quantitative evaluation, using laboratory measures of organ function and porphyrin levels, to evaluate the effectiveness of therapies.
  • Effectiveness and tolerability of currently used and new therapies for the human porphyrias [ Time Frame: year 3 ]
    Qualitative evaluation, using self-reporting questionnaires and clinical findings, and quantitative evaluation, using laboratory measures of organ function and porphyrin levels, to evaluate the effectiveness of therapies.
  • Effectiveness and tolerability of currently used and new therapies for the human porphyrias [ Time Frame: year 4 ]
    Qualitative evaluation, using self-reporting questionnaires and clinical findings, and quantitative evaluation, using laboratory measures of organ function and porphyrin levels, to evaluate the effectiveness of therapies.
  
  
  Information By: Icahn School of Medicine at Mount Sinai
  

  Dates:
  Date Received: February 13, 2012
  Date Started: November 2010
  Date Completion: December 2019
  Last Updated: July 26, 2016
  Last Verified: July 2016