Longitudinal Study of the Porphyrias

March 5, 2024 updated by: Manisha C Balwani, Icahn School of Medicine at Mount Sinai
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.

Study Overview

Status

Recruiting

Conditions

Detailed Description

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 several 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 assemble a well-documented group of patients with confirmed diagnoses of specific porphyrias for clinical, biochemical, and genetic studies. The long-term objective is to conduct a longitudinal investigation of the natural history, complications, and therapeutic outcomes in people with acute and cutaneous porphyria.

Study Type

Observational

Enrollment (Estimated)

1500

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 States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Recruiting
        • University of Alabama, Birmingham
        • Contact:
        • Principal Investigator:
          • Brendan McGuire, MD
    • California
      • Los Angeles, California, United States, 90095
        • Not yet recruiting
        • University of California, Los Angeles
        • Principal Investigator:
          • Simon Beaven, MD, PhD
      • San Francisco, California, United States, 94143
        • Recruiting
        • University of California, San Francisco
        • Contact:
        • Principal Investigator:
          • Bruce Wang, MD
    • Florida
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami
        • Principal Investigator:
          • Cynthia Levy, MD
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Illinois at Chicago
        • Principal Investigator:
          • Sean Quigley, MD
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
        • Principal Investigator:
          • Amy Dickey, MD
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • University of Minnesota
        • Contact:
        • Principal Investigator:
          • Marshall Mazepa, MD
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Icahn School of Medicine at Mount Sinai
        • Contact:
        • Principal Investigator:
          • Manisha Balwani, MD, MS
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Terminated
        • Carolinas Medical Center and HealthCare System
      • Winston-Salem, North Carolina, United States, 27106
        • Recruiting
        • Wake Forest University Health Sciences
        • Contact:
        • Principal Investigator:
          • Herbert L Bonkovsky, MD
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Not yet recruiting
        • Cleveland Clinic
        • Contact:
        • Contact:
          • Allison Schreiber, MS, CGC
          • Phone Number: (216) 444-9249
          • Email: schreia@ccf.org
        • Principal Investigator:
          • Angelika Erwin, MD, PhD
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University
        • Contact:
        • Principal Investigator:
          • Manish Thapar, MD
    • Texas
      • Galveston, Texas, United States, 77555
        • Recruiting
        • University of Texas Medical Branch
        • Contact:
        • Principal Investigator:
          • Karl E. Anderson, MD
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • Recruiting
        • University of Utah
        • Contact:
        • Principal Investigator:
          • John Phillips, PhD
    • Washington
      • Seattle, Washington, United States, 98195
        • Recruiting
        • University of Washington
        • Contact:
        • Principal Investigator:
          • Sioban Keel, MD

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

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Subjects will be recruited from the following resources:

  1. Patients followed by one of the Investigators
  2. United Porphyrias Association (UPA)
  3. Non-study Physician referrals
  4. Self-referrals, including family members of individuals diagnosed with Porphyria (proband) and other individuals who may have heard about the study from other subjects or prospective subjects.
  5. Medical Records Review

Description

Inclusion Criteria:

  • Individuals with a documented diagnosis of a porphyria.

  • For each type of porphyria, the inclusion criteria are based on

    • Biochemical findings, as documented by laboratory reports (or copies) of porphyria-specific testing performed after 1980 (Absolute values are preferred for diagnostic biochemical thresholds. Fold increases in comparison to an upper (or lower) limit of normal (ULN or LLN) are also acceptable, but are complicated by considerable variation between laboratories in normal limits. Equivocal biochemical measurements may require confirmation by a consortium reference laboratory;)
    • molecular findings documenting the identification of a mutation in a porphyria-related gene.
  • In addition, an individual or a parent or guardian must be willing to give written informed consent or assent, as appropriate.
  • Provision is made for enrolling relatives who may not have symptoms but have biochemical or molecular documentation of a porphyria, or in the case of recessive disorders carry a disease-related mutation.

Exclusion Criteria:

  • Cases with elevations of porphyrins in urine, plasma or erythrocytes due to other diseases (i.e. secondary porphyrinuria or porphyrinemia), such as liver and bone marrow diseases;
  • Patients with a prior diagnosis of porphyria that cannot be documented by review of existing medical records or repeat biochemical or DNA testing.

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: Other

Cohorts and Interventions

Group / Cohort
Acute Intermittent Porphyria (AIP)
Patients with a documented diagnosis of AIP
Hereditary Coproporphyria (HCP)
Patients with a documented diagnosis of HCP
Variegate Porphyria (VP)
Patients with a documented diagnosis of VP
Congenital Erythropoietic Porphyria (CEP)
Patients with a documented diagnosis of CEP
Hepatoerythropoietic Porphyria (HEP)
Patients with a documented diagnosis of HEP
Porphyria Cutanea Tarda (PCT)
Patients with a documented diagnosis of PCT
Erythropoietic Protoporphyria (EPP)
Patients with a documented diagnosis of EPP
X-Linked Protoporphyria (XLP)
Patients with a documented diagnosis of XLP
Aminolevulinate-Dehydratase Deficiency Porphyria (ALAD, ADP)
Patients with a documented diagnosis of ALAD, ADP
Homozygous Dominant Acute Hepatic Porphyria
Patients with a documented diagnosis of Homozygous Dominant AHP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
baseline
Laboratory analysis
Time Frame: baseline
To evaluate porphyrin and porphyrin precursor levels alone or by genotype and porphyria subtype
baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
baseline
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.
baseline

Collaborators and Investigators

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

Sponsor

Icahn School of Medicine at Mount Sinai

Investigators

  • Principal Investigator: Manisha C Balwani, MD, Icahn School of Medicine at Mount Sinai

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.

General Publications

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 (Actual)

November 1, 2010

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

June 1, 2025

Study Registration Dates

First Submitted

February 13, 2012

First Submitted That Met QC Criteria

March 21, 2012

First Posted (Estimated)

March 22, 2012

Study Record Updates

Last Update Posted (Estimated)

March 6, 2024

Last Update Submitted That Met QC Criteria

March 5, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GCO 10-1102

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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