Longitudinal Study of the Porphyrias

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Mount Sinai School of Medicine
Sponsor:
Information provided by (Responsible Party):
Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT01561157
First received: February 13, 2012
Last updated: September 19, 2014
Last verified: September 2014
  Purpose

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.


Condition
Acute Porphyrias
Cutaneous Porphyrias

Study Type: Observational
Study Design: Observational Model: Cohort
Official Title: Longitudinal Study of the Porphyrias

Resource links provided by NLM:


Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • clinical analysis [ Time Frame: baseline ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    To evaluate porphyrin and porphyrin precursor levels alone or by genotype and porphyria subtype


Secondary Outcome Measures:
  • Relationship between disease severity and biomarkers [ Time Frame: baseline ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Biospecimen Retention:   Samples With DNA

whole blood, plasma/serum, red blood cells, white cells, urine, stool, tissue, DNA


Estimated Enrollment: 600
Study Start Date: November 2010
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

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 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 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.

  Eligibility

Genders Eligible for Study:   Both
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. The American Porphyria Foundation (APF)
  3. The Rare Diseases Clinical Research Network (RDCRN) Contact Registry
  4. Non-study Physician referrals
  5. 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.
  6. Medical Records Review
Criteria

Inclusion Criteria:

  • Individuals with a documented diagnosis of a porphyria.
  • For each type of porphyria, the inclusion criteria are based on

    • clinical features;
    • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01561157

Contacts
Contact: Hetanshi Naik, MS, CGC 212-241-7699 hetanshi.naik@mssm.edu
Contact: Robert J Desnick, MD, PhD 212-659-6700 robert.desnick@mssm.edu

Locations
United States, Alabama
University of Alabama, Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Joseph R. Bloomer, MD    205-996-9543    jbloomer@uab.edu   
Contact: Toni Seay    205-996-9543    tamartin@uab.edu   
Principal Investigator: Joseph R. Bloomer, MD         
United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: D. Montgomery Bissell, MD    415-476-8405    montgomery.bissell@ucsf.edu   
Contact: Sam Z Abharrodi, BS    (415) 476-8405    Sam.ZenhariAbharrodi@ucsf.edu   
Principal Investigator: D. Montgomery Bissell, MD         
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Robert J Desnick, MD, PhD    212-659-6500    robert.desnick@mssm.edu   
Contact: Sylvia Xistris    212-241-6790    sylvia.xistris@mssm.edu   
Principal Investigator: Robert J Desnick, MD, PhD         
United States, North Carolina
Carolinas Medical Center and HealthCare System Recruiting
Charlotte, North Carolina, United States, 28203
Contact: Herbert L. Bonkovsky, MD    704-355-9645    Herbert.Bonkovsky@carolinashealthcare.org   
Contact: Gale Groseclose, RN    (704) 355-4875    Gale.Grosclose@carolinashealthcare.org   
Principal Investigator: Herbert L. Bonkovsky, MD         
United States, Texas
University of Texas Medical Branch Recruiting
Galveston, Texas, United States, 77555
Contact: Karl E. Anderson, MD    409-772-4661    kanderso@utmb.edu   
Contact: Csilla Hallberg, MD    409-772-6287    challberg@utmb.edu   
Principal Investigator: Karl E. Anderson, MD         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84132
Contact: John Phillips, PhD    801-585-3229    john.phillips@hsc.utah.edu   
Contact: Tiffanie Hales    (801) 213-3367    tiffanie.hales@hsc.utah.edu   
Principal Investigator: John Phillips, PhD         
Sponsors and Collaborators
Mount Sinai School of Medicine
Investigators
Principal Investigator: Robert J Desnick, MD, PhD Mount Sinai School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT01561157     History of Changes
Other Study ID Numbers: GCO 10-1102
Study First Received: February 13, 2012
Last Updated: September 19, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Mount Sinai School of Medicine:
porphyria
acute intermittent
coproporphyria
variegate
erythropoietic
protoporphyria
hepatoerythropoietic
cutanea tarda
AIP
HCP
VP
ADP
ALAD
PCT
HEP
CEP
EPP
XLP

Additional relevant MeSH terms:
Porphyria, Acute Intermittent
Porphyria, Erythropoietic
Porphyrias
Digestive System Diseases
Genetic Diseases, Inborn
Liver Diseases
Metabolic Diseases
Metabolism, Inborn Errors
Porphyrias, Hepatic
Skin Diseases
Skin Diseases, Genetic
Skin Diseases, Metabolic

ClinicalTrials.gov processed this record on October 20, 2014