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Longitudinal Study of the Porphyrias

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ClinicalTrials.gov Identifier: NCT01561157
Recruitment Status : Recruiting
First Posted : March 22, 2012
Last Update Posted : April 13, 2023
Information provided by (Responsible Party):
Manisha C Balwani, Icahn School of Medicine at Mount Sinai

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.

Condition or disease
Acute Porphyrias Cutaneous Porphyrias

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.

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Study Type : Observational
Estimated Enrollment : 1500 participants
Observational Model: Cohort
Time Perspective: Other
Official Title: Longitudinal Study of the Porphyrias
Actual Study Start Date : November 1, 2010
Estimated Primary Completion Date : September 2024
Estimated Study Completion Date : December 2024

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

Primary Outcome Measures :
  1. 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.

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

Secondary Outcome Measures :
  1. 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.

  2. 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.

Biospecimen Retention:   Samples With DNA
whole blood, plasma/serum, red blood cells, urine, tissue, DNA

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Minute and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01561157

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Contact: Mary Freeman, MS, CGC 212-659-1434 mary.freeman@mssm.edu
Contact: Cristoforo Terrasi 917-504-6700 cristoforo.terrasi@mssm.edu

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United States, Alabama
University of Alabama, Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Angelina Johnson    205-934-0498    angeliagjohnson@uabmc.edu   
Principal Investigator: Brendan McGuire, MD         
United States, California
University of California, Los Angeles Not yet recruiting
Los Angeles, California, United States, 90095
Principal Investigator: Simon Beaven, MD, PhD         
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Yuvraaj Kapoor    415-476-8405    yuvraaj.kapoor@ucsf.edu   
Principal Investigator: Bruce Wang, MD         
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Edisson J Aguilera Herrera       eja103@med.miami.edu   
Principal Investigator: Cynthia Levy, MD         
United States, Illinois
University of Illinois at Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Erin Vidra    312-996-7902    evidra@uic.edu   
Principal Investigator: Sean Quigley, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Paul Y Jiang    781-354-9735    pyjiang@mgh.harvard.edu   
Principal Investigator: Amy Dickey, MD         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Diondra Howard       howar709@umn.edu   
Principal Investigator: Marshall Mazepa, MD         
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Alyne Restrepo    929-626-1096    alyne.restrepo@mssm.edu   
Principal Investigator: Manisha Balwani, MD, MS         
United States, North Carolina
Carolinas Medical Center and HealthCare System Terminated
Charlotte, North Carolina, United States, 28203
Wake Forest University Health Sciences Recruiting
Winston-Salem, North Carolina, United States, 27106
Contact: Denise Faust    336-713-1442    delannin@wakehealth.edu   
Principal Investigator: Herbert L Bonkovsky, MD         
United States, Ohio
Cleveland Clinic Not yet recruiting
Cleveland, Ohio, United States, 44195
Contact: Angelika Erwin, MD, PhD       erwina@ccf.org   
Contact: Allison Schreiber, MS, CGC    (216) 444-9249    schreia@ccf.org   
Principal Investigator: Angelika Erwin, MD, PhD         
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Manisha Verma       Manisha.Verma@jefferson.edu   
Principal Investigator: Manish Thapar, MD         
United States, Texas
University of Texas Medical Branch Recruiting
Galveston, Texas, United States, 77555
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: Hina Yazdani    801-587-2506    hina.yazdani@hsc.edu   
Principal Investigator: John Phillips, PhD         
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98195
Contact: Niall Curley    206-288-1231    ncurley8@seattlecca.org   
Principal Investigator: Sioban Keel, MD         
Sponsors and Collaborators
Icahn School of Medicine at Mount Sinai
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Principal Investigator: Manisha C Balwani, MD Icahn School of Medicine at Mount Sinai
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Manisha C Balwani, Professor, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT01561157    
Other Study ID Numbers: GCO 10-1102
First Posted: March 22, 2012    Key Record Dates
Last Update Posted: April 13, 2023
Last Verified: April 2023
Keywords provided by Manisha C Balwani, Icahn School of Medicine at Mount Sinai:
acute intermittent
cutanea tarda
homozygous dominant
acute hepatic
Additional relevant MeSH terms:
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Porphyria, Acute Intermittent
Porphyria, Erythropoietic
Metabolic Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases
Porphyrias, Hepatic
Liver Diseases
Digestive System Diseases