Hereditary Coproporphyria (HCP)NCT01568554
Clinical Diagnosis of Acute Porphyria
An observational study of Hereditary Coproporphyria (HCP) and Acute Intermittent Porphyria (AIP), run by University of California, San Francisco at 6 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Hereditary Coproporphyria (HCP), Acute Intermittent Porphyria (AIP), Variegate Porphyria (VP)
- How many people
- 148 participants
- Where
- 6 sitesUnited States
- Study dates
- Dec 2011to Dec 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
UAB Porphyria Center, University of Alabama at Birmingham
Birmingham, Alabama, 35294
UTMB Porphyria Center, University of Texas Medical Branch
Galveston, Texas, 77555
Mount Sinai Porphyria Comprehensive Diagnostic & Treatment Center, Mount Sinai School of Medicine
New York, New York, 10029
Porphyria Center, University of Utah
Salt Lake City, Utah, 84132
UCSF Porphyria Center, University of California at San Francisco
San Francisco, California, 94143
Wake Forest University School of Medicine
Winston-Salem, North Carolina, 27157
About this study
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.
Read the 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
- Conditions
- Hereditary Coproporphyria (HCP), Acute Intermittent Porphyria (AIP), Variegate Porphyria (VP)
- Medical subject headings
- Coproporphyria, Hereditary, Porphyria, Acute Intermittent, Porphyria, Variegate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
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.
Measured: Assessed annually for 5 years
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.
Measured: Assessed once enrollment and genetic testing of subjects in Group 2 are complete - after a 1-year recruitment and enrollment period.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2012 (estimated)
- Study startDec 2011
- Primary completionDec 2018
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hereditary Coproporphyria (HCP)Studies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 148 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- University of Texas, University of Alabama at Birmingham, Icahn School of Medicine at Mount Sinai, University of Utah, Carolinas Medical Center, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Rare Diseases Clinical Research Network
- Responsible party
- Sponsor
- Investigators
- Bruce Wang, M.D., Study chair, University of California at San FranciscoKarl E. Anderson, M.D., Principal investigator, University of TexasJoseph R. Bloomer, M.D., Principal investigator, University of Alabama at BirminghamRobert J. Desnick, Ph.D., M.D., Principal investigator, Icahn School of Medicine at Mount SinaiJames P. Kushner, M.D., Principal investigator, University of UtahHerbert L. Bonkovsky, M.D., Principal investigator, Carolinas Medical Center and HealthCare System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01568554
- Sponsor's protocol ID
- PC7204
- Other IDs
- 1U54DK083909
- Status last verified
- Sep 2021
- First submitted
- 16 Feb 2012
- Last updated
- 28 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Diagnosis of Acute Porphyria
- ClinicalTrials.gov ID
- NCT01568554
- Acronym / sponsor ID
- PC7204
- Conditions
- Hereditary Coproporphyria (HCP), Acute Intermittent Porphyria (AIP), Variegate Porphyria (VP)
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 148 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- University of Texas, University of Alabama at Birmingham, Icahn School of Medicine at Mount Sinai, University of Utah, Carolinas Medical Center, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Rare Diseases Clinical Research Network
- Study start
- Dec 2011
- Primary completion
- Dec 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 2 Apr 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Presence of positive biochemical features by first-line testing in subjects suspected of being a genetic carrier of acute porphyria
Time frame: Assessed once at baseline visit for all subjects
All subjects will be assessed for any elevation of quantitative urine porphobilinogen (PBG).
Presence of positive biochemical features by second-line testing in subjects suspected of being a genetic carrier of acute porphyria
Time frame: Assessed once at baseline visit for all subjects
All subjects will be assessed for any elevations of fractionated quantitative urine porphyrins.
Presence of positive biochemical features by second-line testing in subjects suspected of being a genetic carrier of acute porphyria
Time frame: Assessed once at baseline visit for all subjects
All subjects will be assessed for any elevations and levels of fractionated quantitative fecal porphyrins.
Clinical features suggestive of the acute porphyria carrier state
Time frame: 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
Time frame: 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.
Other possible causes of mildly elevated porphyrins and recurrent pain
Time frame: 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.
Presence of heavy metals
Time frame: 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
Time frame: 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.
2 secondary outcomes
Frequency of disease manifestations in genetically confirmed AIP and HCP
Time frame: Assessed annually for 5 years
Prevalence of HCP in a population with elevation of urine coproporphyrin and pain symptoms.
Time frame: Assessed once enrollment and genetic testing of subjects in Group 2 are complete - after a 1-year recruitment and enrollment period.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bruce Wang, M.D. study chair
University of California at San Francisco
Karl E. Anderson, M.D. principal investigator
University of Texas
Joseph R. Bloomer, M.D. principal investigator
University of Alabama at Birmingham
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hereditary Coproporphyria (HCP) and Acute Intermittent Porphyria (AIP), run by University of California, San Francisco at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Presence of positive biochemical features by first-line testing in subjects suspected of being a genetic carrier of acute porphyria (time frame: Assessed once at baseline visit for all subjects). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2021.