Clinical Diagnosis of Acute Porphyria

Acute Intermittent Porphyria (AIP) Clinical Trial

Official title:

Clinical Diagnosis of Acute Porphyria

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01568554
• Other study ID #: PC7204
• Secondary ID: 1U54DK083909
• Status: Completed
• Start date: December 2011
• Est. completion date: December 2018

Study information

• Verified date: September 2021
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 148
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Intermittent Porphyria (AIP)
• Hereditary Coproporphyria (HCP)
• Porphyria, Acute Intermittent
• Porphyria, Erythropoietic
• Porphyrias
• Variegate Porphyria (VP)

Locations

Country	Name	City	State
United States	UAB Porphyria Center, University of Alabama at Birmingham	Birmingham	Alabama
United States	UTMB Porphyria Center, University of Texas Medical Branch	Galveston	Texas
United States	Mount Sinai Porphyria Comprehensive Diagnostic & Treatment Center, Mount Sinai School of Medicine	New York	New York
United States	Porphyria Center, University of Utah	Salt Lake City	Utah
United States	UCSF Porphyria Center, University of California at San Francisco	San Francisco	California
United States	Wake Forest University School of Medicine	Winston-Salem	North Carolina

Sponsors (8)

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

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Frequency of disease manifestations in genetically confirmed AIP and HCP	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.	Assessed annually for 5 years
Secondary	Prevalence of HCP in a population with elevation of urine coproporphyrin and pain symptoms.	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.	Assessed once enrollment and genetic testing of subjects in Group 2 are complete - after a 1-year recruitment and enrollment period.