Clinical trial NCT01568554: Clinical Diagnosis of Acute Porphyria
Official title: Clinical Diagnosis of Acute Porphyria
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hereditary Coproporphyria (HCP)
Acute Intermittent Porphyria (AIP)
Variegate Porphyria (VP)
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: University of Texas
name: University of Alabama at Birmingham
name: Icahn School of Medicine at Mount Sinai
name: University of Utah
name: Carolinas Medical Center
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Rare Diseases Clinical Research Network
First posted: 2012-04-02
Enrollment: 148
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Detailed description: The porphyrias are a group of genetic diseases caused by disturbances in the formation of heme, an essential component of hemoglobin and other proteins, leading to either acute (neurologic) and/or chronic (cutaneous) symptoms. Acute porphyria is often difficult to diagnose because symptoms may not be specific and, unless the patient is in an active attack, laboratory values typically may not be useful for diagnosing porphyria. The purpose of this study is to test whether a focused questionnaire and laboratory evaluation tool can better define risk factors associated with possible genetic porphyria. The goals of this study are:

* To determine the presence and number of abnormal lab tests and porphyria-like symptoms in adult family members of the first person in a family who has been diagnosed with a disease of acute porphyria, 50% of whom are expected to carry the same genetic defect of the index case.
* To devise a Genetic Carrie Profile that could be used to screen people in whom the diagnosis of porphyria is being considered.
* To test the Profile in patients with symptoms suggestive of HCP and/or urine tests showing some elevation of porphyrins.
* To explain other possible causes of minor increases in porphyrin levels in patients with recurrent abdominal pain who have not been diagnosed with porphyria

Eligibility criteria: Group 1 Inclusion Criteria:

* 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

Group 2 Inclusion Criteria:

* 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

Groups 1 and 2 Exclusion Criteria:

* 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).

Follow Up Sub-Study (Group 3) Inclusion Criteria:

* 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

Follow Up Sub-Study (Group 3) Exclusion Criteria:

* You have been seen by the Porphyria Consortium physician/investigator less than 10 years prior to study initiation.

Primary outcomes:
measure: Presence of positive biochemical features by first-line testing in subjects suspected of being a genetic carrier of acute porphyria
timeFrame: Assessed once at baseline visit for all subjects
measure: Presence of positive biochemical features by second-line testing in subjects suspected of being a genetic carrier of acute porphyria
timeFrame: Assessed once at baseline visit for all subjects
measure: Presence of positive biochemical features by second-line testing in subjects suspected of being a genetic carrier of acute porphyria
timeFrame: Assessed once at baseline visit for all subjects
measure: Clinical features suggestive of the acute porphyria carrier state
timeFrame: Assessed once at baseline visit for all subjects
measure: Acute porphyria genetic carrier state
timeFrame: Assessed once at baseline visit for all subjects
measure: Other possible causes of mildly elevated porphyrins and recurrent pain
timeFrame: Assessed once during a one-time telephone or in-person interview
measure: Presence of heavy metals
timeFrame: Assessed once at baseline visit for all subjects
measure: Validity of Genetic Carrier Profile
timeFrame: The profile will be tested once during the baseline visit for subjects in Group 2.
Secondary outcomes:
measure: Frequency of disease manifestations in genetically confirmed AIP and HCP
timeFrame: Assessed annually for 5 years
measure: Prevalence of HCP in a population with elevation of urine coproporphyrin and pain symptoms.
timeFrame: Assessed once enrollment and genetic testing of subjects in Group 2 are complete - after a 1-year recruitment and enrollment period.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Porphyria Center, University of Alabama at Birmingham
state: Alabama
city: San Francisco
country: United States
facility: UCSF Porphyria Center, University of California at San Francisco
state: California
city: New York
country: United States
facility: Mount Sinai Porphyria Comprehensive Diagnostic & Treatment Center, Mount Sinai School of Medicine
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Galveston
country: United States
facility: UTMB Porphyria Center, University of Texas Medical Branch
state: Texas
city: Salt Lake City
country: United States
facility: Porphyria Center, University of Utah
state: Utah
Study officials:
affiliation: University of California at San Francisco
name: Bruce Wang, M.D.
role: STUDY_CHAIR
affiliation: University of Texas
name: Karl E. Anderson, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Joseph R. Bloomer, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Robert J. Desnick, Ph.D., M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Utah
name: James P. Kushner, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Carolinas Medical Center and HealthCare System
name: Herbert L. Bonkovsky, M.D.
role: PRINCIPAL_INVESTIGATOR
References: