Clinical Diagnosis of Acute Porphyria

NCT01568554 | Completed DMC

• 2 other identifiers: PC72041U54DK083909
• Study Type: observational
• Target: 148
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to test whether a focused questionnaire and laboratory tests can better define risk factors associated with possible genetic porphyria. The investigators hypothesize that the genetic carrier state of acute porphyria is distinctive enough that the Genetic Carrier Profile the investigators devise through this study will be useful in identifying carriers of genetic porphyria among the large population with undiagnosed abdominal pain.

Conditions

Hereditary Coproporphyria (HCP); Acute Intermittent Porphyria (AIP); Variegate Porphyria (VP)

Outcome Measures

Primary Outcomes (8)

• Presence of positive biochemical features by first-line testing in subjects suspected of being a genetic carrier of acute porphyria

  All subjects will be assessed for any elevation of quantitative urine porphobilinogen (PBG).

  Assessed once at baseline visit for all subjects

• Presence of positive biochemical features by second-line testing in subjects suspected of being a genetic carrier of acute porphyria

  All subjects will be assessed for any elevations of fractionated quantitative urine porphyrins.

  Assessed once at baseline visit for all subjects

• Presence of positive biochemical features by second-line testing in subjects suspected of being a genetic carrier of acute porphyria

  All subjects will be assessed for any elevations and levels of fractionated quantitative fecal porphyrins.

  Assessed once at baseline visit for all subjects

• Clinical features suggestive of the acute porphyria carrier state

  Through a focused questionnaire, we will determine the typical duration of pain attacks.

  Assessed once at baseline visit for all subjects

• Acute porphyria genetic carrier state

  All subjects will undergo DNA analysis to detect a mutation in the HMBS, CPOX, or PPOX genes, respectively.

  Assessed once at baseline visit for all subjects

• Other possible causes of mildly elevated porphyrins and recurrent pain

  Participants in the Follow-up Sub-study section of this protocol will be interviewed concerning other possible causes of mildly elevated porphyins and recurrent pain. These will be patients previously seen by the investigator who were deemed not to have porphyria.

  Assessed once during a one-time telephone or in-person interview

• Presence of heavy metals

  All subjects will undergo a blood test to screen for the presence of heavy metals as a cause for minor elevations of porphyrin levels.

  Assessed once at baseline visit for all subjects

• Validity of Genetic Carrier Profile

  The biochemical and clinical features of genetically proven but asymptomatic HCP will be tabulated and compared to subjects who are not genetic carriers. Its accuracy in predicting risk factors for HCP will be tested in subjects in Group 2.

  The profile will be tested once during the baseline visit for subjects in Group 2.

Secondary Outcomes (2)

• Frequency of disease manifestations in genetically confirmed AIP and HCP

  Assessed annually for 5 years

• Prevalence of HCP in a population with elevation of urine coproporphyrin and pain symptoms.

  Assessed once enrollment and genetic testing of subjects in Group 2 are complete - after a 1-year recruitment and enrollment period.

Study Arms (3)

Group 1

Group 1 will include subjects 15 years of age or older who are a first-degree relative (child, sibling, parent, or grandparent) of an individual with genetically proven acute porphyria (AIP, HCP or VP), and have not had any previous genetic testing for porphyria themselves.

Group 2 (Not Yet Enrolling)

Group 2 will consist of subjects 15 years of age or older who have a history of clinical features suggestive of acute porphyria, such as such as abdominal, back or limb pain, recurrent nausea lasting days, reaction to medications, psychiatric history, or sun sensitivity, and an increase in urinary, fecal or serum porphobilinogen (PBG) and/or porphyrins.

Group 3

Subjects in Group 3 will participate in the "Follow Up Sub-Study." This group will include individuals who have been seen by one of the Porphyria Consortium physicians/investigators for suspicion of porphyria 10 or more years prior to study initiation, but were not given a diagnosis of porphyria at the time of their initial visit.

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Group 1: Individuals who are first-degree relatives of a patient with one of the acute porphyrias (AIP, HCP, VP). They will complete questionnaires and laboratory tests, including genetic testing for porphyria. The data will be used to develop a clinical profile for the risk factors associated with the genetic carrier state. Group 2: Subjects who possibly have acute porphyria, but do not have a confirmed diagnosis based on genetic testing. They will serve to test the validity of the clinical index derived from Group 1. Group 3: Patients who have been seen by one of the Porphyria Consortium physicians/investigators 10 or more years ago, but were not given a diagnosis of porphyria. They will complete a questionnaire to determine whether they received a porphyria diagnosis, or another diagnosis that might explain the initial presentation.

You may qualify if:

• Be 15 years of age or older
• Be a first-degree relative (child, sibling, parent, or grandparent) of an individual with genetically proven acute porphyria (AIP, HCP or VP)
• Not have had any previous genetic testing for acute porphyria
• Be 15 years of age or older
• Have a history of suggestive clinical features, such as abdominal, back or limb pain, recurrent nausea lasting days, reaction to medications, psychiatric history, or sun sensitivity.
• An increase in urinary, fecal or serum porphobilinogen (PBG) and/or porphyrins

You may not qualify if:

• Have previously had genetic testing for acute porphyria
• Have a history of "alarm" symptoms, such as anemia, unintentional weight loss, signs of GI (gastrointestinal) bleeding, or dysphagia (difficulty in swallowing).
• Have been seen by one of the Porphyria Consortium physicians/investigators 10 or more years prior to study initiation
• Had a slight increase in porphyrins during the initial visit
• Not given a diagnosis of porphyria at the time of the visit
• You have been seen by the Porphyria Consortium physician/investigator less than 10 years prior to study initiation.

Sponsors & Collaborators

• University of California, San Francisco: lead
• University of Texas: collaborator
• University of Alabama at Birmingham: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator
• University of Utah: collaborator
• Carolinas Medical Center: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Rare Diseases Clinical Research Network: collaborator

Study Sites (6)

UAB Porphyria Center, University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

UCSF Porphyria Center, University of California at San Francisco

San Francisco, California, 94143, United States

Location

Mount Sinai Porphyria Comprehensive Diagnostic & Treatment Center, Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Wake Forest University School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

UTMB Porphyria Center, University of Texas Medical Branch

Galveston, Texas, 77555, United States

Location

Porphyria Center, University of Utah

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Conditions

Coproporphyria, Hereditary; Porphyria, Acute Intermittent; Porphyria, Variegate

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; Porphyrias; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Bruce Wang, M.D.

  University of California at San Francisco

  STUDY CHAIR

• Karl E. Anderson, M.D.

  University of Texas

  PRINCIPAL INVESTIGATOR

• Joseph R. Bloomer, M.D.

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Robert J. Desnick, Ph.D., M.D.

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• James P. Kushner, M.D.

  University of Utah

  PRINCIPAL INVESTIGATOR

• Herbert L. Bonkovsky, M.D.

  Carolinas Medical Center and HealthCare System

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 16, 2012
• First Posted: April 2, 2012
• Study Start: December 1, 2011
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: September 28, 2021

Record last verified: 2021-09

Locations

US (6)