Erythropoietic Protoporphyrias: Studies of the Natural History, Genotype-Phenotype Correlations, and Psychosocial Impact

NCT01688895 | Completed Results DMC

• 3 other identifiers: GCO 08-0959-04HSM12-00307U54DK083909
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 6

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.

Conditions

Erythropoietic Protoporphyria; EPP; X-Linked Protoporphyria; XLP; XLPP; X-Linked Dominant Erythropoietic Protoporphyria; XLEPP; XLDP

Keywords

erythropoietic; protoporphyria; cutaneous; porphyria

Outcome Measures

Primary Outcomes (3)

• The Hospital Anxiety and Depression Scale (HADS)

  Questionnaire with 7 items for anxiety and 7 items for depression, each item is scored on a 4 point response 0 - 3, subscales 0-21, with full range from 0 to 42, with higher score indicating more severe anxiety or depression.

  1 weeks

• Illness Perception Questionnaire Revised (IPQR)

  Each item is scored on a likert scale from 1 (strongly disagree) to 5 (strongly agree). Items within each domain were totaled for final domain scores. Seven domains - Timeline (score 5-25), Consequences (score 6-30), Personal Control (score 6-30), Treatment Control (score 3-15), Illness Coherence (score 5-25), Timeline-Cyclical (score 4-20), and Emotional Representations (score 6-30). A modified version without the identity component was used as it was not applicable in EPP. Higher scores domains indicate overall strong beliefs that the disease is chronic and has a negative impact.

  1 week

• EPP-Specific Tool

  Each item was scored from 0-3 on a Likert scale. There are 2 domains: S=disease severity and Q=QoL. Total scale for each domain transferred to 0-100 scale. Higher scores for the S domain reflect lower severity, and higher satisfaction/QoL for the Q domain. Total Score from 0-100, with higher score indicating higher quality of life.

  1 week

Secondary Outcomes (1)

• Sleep Disturbance PROMIS Scores

  baseline

Study Arms (1)

Participants with Protoporphyrias

Individuals with a documented diagnosis of Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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:
• A disease causing FECH mutation trans to the IVS3-48C\>T low expression FECH allele
• Two disease-causing FECH mutations
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• Rare Diseases Clinical Research Network: collaborator
• Office of Rare Diseases (ORD): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (6)

University of Alabama, Birmingham

Birmingham, Alabama, 35294-0012, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27106, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Links

• Website for the Rare Diseases Clinical Research Network (RDCRN) Porphyrias Consortium (PC)

Biospecimen

Retention: SAMPLES WITH DNA

DNA extracted from peripheral blood sample or buccal (inside cheek) sampling for DNA analysis; whole blood in ACD anti-coagulant to establish a lymphoid cell line, red blood cells and plasma for biochemical assays.

MeSH Terms

Conditions

Protoporphyria, Erythropoietic; Protoporphyria, Erythropoietic, X-Linked Dominant; Porphyrias

Condition Hierarchy (Ancestors)

Porphyrias, Hepatic; Liver Diseases; Digestive System Diseases; Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Dr. Hetanshi Naik
• Organization: Icahn School of Medicine at Mount Sinai

hetanshi.naik@mssm.edu

212-241-7699

Study Officials

• Manisha Balwani, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2012
• First Posted: September 20, 2012
• Study Start: July 1, 2012
• Primary Completion: July 1, 2019
• Study Completion: July 1, 2019
• Last Updated: April 17, 2020
• Results First Posted: April 17, 2020

Record last verified: 2020-04

Locations

US (6)