Clinical Diagnosis of Acute Porphyria

Completed

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

• Registration Number: NCT01568554
• Lead Sponsor: University of California, San Francisco

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

Study Timeline

• Study Start: 2011-12
• Study First Submitted: 2012-02-16
• Study First Submitted QC: 2012-03-30
• Study First Posted: 2012-04-02
• Primary Completion: 2018-12
• Study Completion: 2018-12
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-22
• Last Update Posted: 2021-09-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 148

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

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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.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Other possible causes of mildly elevated porphyrins and recurrent pain	Assessed once during a one-time telephone or in-person interview	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.
Clinical features suggestive of the acute porphyria carrier state	Assessed once at baseline visit for all subjects	Through a focused questionnaire, we will determine the typical duration of pain attacks.
Acute porphyria genetic carrier state	Assessed once at baseline visit for all subjects	All subjects will undergo DNA analysis to detect a mutation in the HMBS, CPOX, or PPOX genes, respectively.
Presence of heavy metals	Assessed once at baseline visit for all subjects	All subjects will undergo a blood test to screen for the presence of heavy metals as a cause for minor elevations of porphyrin levels.
Validity of Genetic Carrier Profile	The profile will be tested once during the baseline visit for subjects in Group 2.	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.
Presence of positive biochemical features by second-line testing in subjects suspected of being a genetic carrier of acute porphyria	Assessed once at baseline visit for all subjects	All subjects will be assessed for any elevations and levels of fractionated quantitative fecal porphyrins.
Presence of positive biochemical features by first-line testing in subjects suspected of being a genetic carrier of acute porphyria	Assessed once at baseline visit for all subjects	All subjects will be assessed for any elevation of quantitative urine porphobilinogen (PBG).

Secondary Outcome Measures

Name	Time	Method
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.	Based on the number of subjects in Group 2 determined by DNA analysis to have HCP, we will approximate the prevalence of HCP in a population with elevations in coproporphyrin and pain symptoms that are undiagnosed.
Frequency of disease manifestations in genetically confirmed AIP and HCP	Assessed annually for 5 years	Subjects who are confirmed to have AIP and HCP will be assessed at annual follow up visits for the presence and frequency of porphyria symptoms.

Trial Locations

Locations (6)

UCSF Porphyria Center, University of California at San Francisco; 🇺🇸 San Francisco, California, United States

UTMB Porphyria Center, University of Texas Medical Branch; 🇺🇸 Galveston, Texas, United States

Porphyria Center, University of Utah; 🇺🇸 Salt Lake City, Utah, United States

UAB Porphyria Center, University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Wake Forest University School of Medicine; 🇺🇸 Winston-Salem, North Carolina, United States

Mount Sinai Porphyria Comprehensive Diagnostic & Treatment Center, Mount Sinai School of Medicine; 🇺🇸 New York, New York, United States