Clinical trial NCT01688895: Erythropoietic Protoporphyrias: Studies of the Natural History, Genotype-Phenotype Correlations, and Psychosocial Impact
Official title: Erythropoietic Protoporphyrias: Studies of the Natural History, Genotype-Phenotype Correlations, and Psychosocial Impact
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Erythropoietic Protoporphyria
EPP
X-Linked Protoporphyria
XLP
XLPP
X-Linked Dominant Erythropoietic Protoporphyria
XLEPP
XLDP
Keywords: erythropoietic
protoporphyria
cutaneous
porphyria
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: Rare Diseases Clinical Research Network
name: Office of Rare Diseases (ORD)
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2012-09-20
Enrollment: 150
Sex: ALL
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. 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

Brief summary: The initial objective of this protocol is to assemble a well-documented group of patients with confirmed diagnoses of the erythropoietic protoporphyrias, including autosomal recessive Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP) for clinical, biochemical, and genetic studies. The long-term objectives are (1) to conduct a longitudinal investigation of the natural history, complications, and therapeutic outcomes in people with erythropoietic protoporphyria, (2) to systematically investigate the psychological effects of the erythropoietic protoporphyrias on children and adults, and (3) to investigate the correlation between the identified genotypes and the resulting clinical presentation, also determining the possible interaction of other genetic markers.

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 (as in the acute or hepatic porphyrias), or cutaneous photosensitivity (as in the cutaneous porphyrias, including the erythropoietic protoporphyrias). 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 study of a large group of patients with EPP and XLP 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. Much of the data collected on subjects as participants in the Longitudinal Study of the Porphyrias will be accessed for this study specific to the investigation of the erythropoietic protoporphyrias. To maximize the information that can be informative in our objectives, additional data will be collected, including additional biochemical findings and EPP-specific psychosocial parameters.

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 this study. Additional centers may be added if funding is available.

Eligibility criteria: Inclusion Criteria:

* All subjects must also be enrolled in the Longitudinal Study of the Porphyrias.
* Willing to sign informed consent form
* Biochemical findings - A marked increase in erythrocyte protoporphyrin \[total erythrocyte protoporphyrin \>200 ug/dL, or more than 1.5-fold increase (relative to ULN of 80 ug/dL)\], with a predominance of free protoporphyrin (85-100% in EPP and 50-85% in XLP).
* Molecular findings - one of the following:

  1. A disease causing FECH mutation trans to the IVS3-48C\>T low expression FECH allele
  2. Two disease-causing FECH mutations
  3. A gain-of-function ALAS-2 C-terminal deletion/exon 11 mutation (in XLP). If no mutation is found and subjects fulfill criteria 1-3 they are eligible for enrollment.

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 \[Gibson 2000\].
* 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: The Hospital Anxiety and Depression Scale (HADS)
timeFrame: 1 weeks
measure: Illness Perception Questionnaire Revised (IPQR)
timeFrame: 1 week
measure: EPP-Specific Tool
timeFrame: 1 week
Secondary outcomes:
measure: Sleep Disturbance PROMIS Scores
timeFrame: baseline
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Birmingham
state: Alabama
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
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
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Manisha Balwani, MD
role: PRINCIPAL_INVESTIGATOR
References: