Clinical trial NCT01561157: Longitudinal Study of the Porphyrias
Official title: Longitudinal Study of the Porphyrias
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Acute Porphyrias
Cutaneous Porphyrias
Keywords: porphyria
acute intermittent
coproporphyria
variegate
erythropoietic
protoporphyria
hepatoerythropoietic
cutanea tarda
AIP
HCP
VP
ADP
ALAD
PCT
HEP
CEP
EPP
XLP
homozygous dominant
acute hepatic
AHP
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2012-03-22
Enrollment: 1500
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
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

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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: clinical analysis
timeFrame: baseline
measure: Laboratory analysis
timeFrame: baseline
Secondary outcomes:
measure: Relationship between disease severity and biomarkers
timeFrame: baseline
measure: Effectiveness and tolerability of currently used and new therapies for the human porphyrias
timeFrame: baseline
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center and HealthCare System
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Manisha C Balwani, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Balwani M, Naik H, Anderson KE, Bissell DM, Bloomer J, Bonkovsky HL, Phillips JD, Overbey JR, Wang B, Singal AK, Liu LU, Desnick RJ. Clinical, Biochemical, and Genetic Characterization of North American Patients With Erythropoietic Protoporphyria and X-linked Protoporphyria. JAMA Dermatol. 2017 Aug 1;153(8):789-796. doi: 10.1001/jamadermatol.2017.1557.
citation: Saberi B, Naik H, Overbey JR, Erwin AL, Anderson KE, Bissell DM, Bonkovsky HL, Phillips JD, Wang B, K Singal A, M McGuire B, Desnick RJ, Balwani M. Hepatocellular Carcinoma in Acute Hepatic Porphyrias: Results from the Longitudinal Study of the U.S. Porphyrias Consortium. Hepatology. 2021 May;73(5):1736-1746. doi: 10.1002/hep.31460. Epub 2020 Dec 11.
citation: Levy C, Naik H, Overbey J, Hedstrom K, Wang K, McDonough C, Freeman M, Keel SB, Erwin AL, Dickey AK, Leaf RK, Quigley J, Mazepa M, Wang B, Phillips J, Parker C, McGuire B, Kazamel M, Bonkovsky H, Rudnick S, Anderson KE, Moghe A, Thapar M, Saberi B, Wheeden K, Desnick R, Balwani M; Porphyrias Consortium of the Rare Diseases Clinical Research Network. Liver involvement in a large cohort of patients with erythropoietic protoporphyria or X-linked protoporphyria. Hepatol Commun. 2025 Feb 19;9(3):e0657. doi: 10.1097/HC9.0000000000000657. eCollection 2025 Mar 1.
citation: Bonkovsky HL, Maddukuri VC, Yazici C, Anderson KE, Bissell DM, Bloomer JR, Phillips JD, Naik H, Peter I, Baillargeon G, Bossi K, Gandolfo L, Light C, Bishop D, Desnick RJ. Acute porphyrias in the USA: features of 108 subjects from porphyrias consortium. Am J Med. 2014 Dec;127(12):1233-41. doi: 10.1016/j.amjmed.2014.06.036. Epub 2014 Jul 10.