Erythropoietic ProtoporphyriaNCT01688895
Erythropoietic Protoporphyrias: Studies of the Natural History, Genotype-Phenotype Correlations, and Psychosocial Impact
An observational study of Erythropoietic Protoporphyria and EPP, run by Icahn School of Medicine at Mount Sinai at 6 sites in United States.
Trial summary
The initial objective of this protocol is to assemble a well-documented group of patients with confirmed diagnoses of the erythropoietic protoporphyrias, including autosomal recessive Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP) for clinical, biochemical, and genetic studies. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Erythropoietic Protoporphyria, EPP, X-Linked Protoporphyria
- How many people
- 150 participants
- Where
- 6 sitesUnited States
- Study dates
- Jul 2012to 1 Jul 2019
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Subjects will be recruited from the following resources: 1. Patients followed by one of the Investigators 2. The American Porphyria Foundation (APF) 3. The Rare Diseases Clinical Research Network (RDCRN) Contact Registry 4. Non-study Physician referrals 5. Self-referrals, including family members of individuals diagnosed with Porphyria (proband) and other individuals who may have heard about the study from other subjects or prospective subjects. 6. Medical Records Review
Who may be able to join
- All subjects must also be enrolled in the Longitudinal Study of the Porphyrias.
- Willing to sign informed consent form
- Biochemical findings - A marked increase in erythrocyte protoporphyrin [total erythrocyte protoporphyrin >200 ug/dL, or more than 1.5-fold increase (relative to ULN of 80 ug/dL)], with a predominance of free protoporphyrin (85-100% in EPP and 50-85% in XLP).
- Molecular findings - one of the following:
- A disease causing FECH mutation trans to the IVS3-48C>T low expression FECH allele
- Two disease-causing FECH mutations
- A gain-of-function ALAS-2 C-terminal deletion/exon 11 mutation (in XLP). If no mutation is found and subjects fulfill criteria 1-3 they are eligible for enrollment.
Who cannot join
- cases with elevations of porphyrins in urine, plasma or erythrocytes due to other diseases (i.e. secondary porphyrinuria or porphyrinemia), such as liver and bone marrow diseases [Gibson 2000].
- patients with a prior diagnosis of porphyria that cannot be documented by review of existing medical records or repeat biochemical or DNA testing.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
University of Alabama, Birmingham
Birmingham, Alabama, 35294-0012
University of Texas Medical Branch
Galveston, Texas, 77555
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
University of Utah
Salt Lake City, Utah, 84132
University of California, San Francisco
San Francisco, California, 94143
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27106
About this study
The initial objective of this protocol is to assemble a well-documented group of patients with confirmed diagnoses of the erythropoietic protoporphyrias, including autosomal recessive Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP) for clinical, biochemical, and genetic studies. The long-term objectives are (1) to conduct a longitudinal investigation of the natural history, complications, and therapeutic outcomes in people with erythropoietic protoporphyria, (2) to systematically investigate the psychological effects of the erythropoietic protoporphyrias on children and adults, and (3) to investigate the correlation between the identified genotypes and the resulting clinical presentation, also determining the possible interaction of other genetic markers.
Read the detailed description
The porphyrias are a group of rare metabolic diseases that may present in childhood or adult life and are due to deficiencies of enzymes in the heme biosynthetic pathway. The most common manifestations are related to accumulation of intermediates in the pathway and usually occur as acute neurological attacks (as in the acute or hepatic porphyrias), or cutaneous photosensitivity (as in the cutaneous porphyrias, including the erythropoietic protoporphyrias). Multiple mutations have been identified in each of the porphyrias. The risk of disability or death from these disorders is significant, in part because diagnosis is often delayed due to lack of adoption of diagnostic testing in clinical practice. Moreover, the natural history of these disorders is not well described and it is not known what determines differences in outcomes. New therapies are needed. For existing therapies, high-quality evidence on short and long term efficacy and safety is generally lacking. Therefore, the purpose of this study of a large group of patients with EPP and XLP is to provide a better understanding of the natural history of these disorders, as affected by available therapies, and to aid in developing new forms of treatment. Much of the data collected on subjects as participants in the Longitudinal Study of the Porphyrias will be accessed for this study specific to the investigation of the erythropoietic protoporphyrias. To maximize the information that can be informative in our objectives, additional data will be collected, including additional biochemical findings and EPP-specific psychosocial parameters.
The Office of Rare Diseases (ORD) of the National Institutes of Health (NIH) established a Rare Diseases Clinical Research Network (RDCRN) in collaboration with other NIH Institutes and currently has funded 19 rare diseases clinical research consortia and one Data Management and Coordinating Center. The Porphyrias Consortium was created as part of the RDCRN, to study the human porphyrias. The Porphyrias Consortium is a consortium of the academic institutions listed in the participating institutions table. All Centers in the Porphyrias Consortium are participating in this study. Additional centers may be added if funding is available.
- Conditions
- Erythropoietic Protoporphyria, EPP, X-Linked Protoporphyria, XLP, XLPP, X-Linked Dominant Erythropoietic Protoporphyria
- Keywords
- erythropoietic, protoporphyria, cutaneous, porphyria
- Medical subject headings
- Protoporphyria, Erythropoietic, Protoporphyria, Erythropoietic, X-Linked Dominant, Porphyrias
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 |
|---|---|---|
| Participants with Protoporphyrias | Individuals with a documented diagnosis of Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Hospital Anxiety and Depression Scale (HADS)
Questionnaire with 7 items for anxiety and 7 items for depression, each item is scored on a 4 point response 0 - 3, subscales 0-21, with full range from 0 to 42, with higher score indicating more severe anxiety or depression.
Measured: 1 weeks
Illness Perception Questionnaire Revised (IPQR)
Each item is scored on a likert scale from 1 (strongly disagree) to 5 (strongly agree). Items within each domain were totaled for final domain scores.
Seven domains - Timeline (score 5-25), Consequences (score 6-30), Personal Control (score 6-30), Treatment Control (score 3-15), Illness Coherence (score 5-25), Timeline-Cyclical (score 4-20), and Emotional Representations (score 6-30). A modified version without the identity component was used as it was not applicable in EPP.
Higher scores domains indicate overall strong beliefs that the disease is chronic and has a negative impact.
Measured: 1 week
EPP-Specific Tool
Each item was scored from 0-3 on a Likert scale. There are 2 domains: S=disease severity and Q=QoL. Total scale for each domain transferred to 0-100 scale. Higher scores for the S domain reflect lower severity, and higher satisfaction/QoL for the Q domain. Total Score from 0-100, with higher score indicating higher quality of life.
Measured: 1 week
Secondary outcomes (1)
Sleep Disturbance PROMIS Scores
Sleep Subscales: Pain Interference, Depression, Physical Function, Fatigue, Anxiety, Sleep Disturbance, Satisfaction with Social Roles, each subscale scored from 0-100 with higher score indicating more symptoms affecting sleep.
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2012 (estimated)
- Study startJul 2012
- Primary completion1 Jul 2019
- Study completion1 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Erythropoietic ProtoporphyriaStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe 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
- Other
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Collaborators
- Rare Diseases Clinical Research Network, Office of Rare Diseases (ORD), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Sponsor
- Investigators
- Manisha Balwani, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01688895
- Sponsor's protocol ID
- GCO 08-0959-04
- Other IDs
- HSM12-00307, U54DK083909
- Status last verified
- Apr 2020
- First submitted
- 14 Sep 2012
- Last updated
- 17 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Erythropoietic Protoporphyrias: Studies of the Natural History, Genotype-Phenotype Correlations, and Psychosocial Impact
- ClinicalTrials.gov ID
- NCT01688895
- Acronym / sponsor ID
- GCO 08-0959-04
- Conditions
- Erythropoietic Protoporphyria, EPP, X-Linked Protoporphyria, XLP, XLPP, X-Linked Dominant Erythropoietic Protoporphyria
- Keywords
- erythropoietic, protoporphyria, cutaneous, porphyria
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Collaborators
- Rare Diseases Clinical Research Network, Office of Rare Diseases (ORD), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Jul 2012
- Primary completion
- 1 Jul 2019 (actual)
- Study completion
- 1 Jul 2019 (actual)
- First posted
- 20 Sep 2012 (estimated)
- Results
- Posted 17 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The initial objective of this protocol is to assemble a well-documented group of patients with confirmed diagnoses of the erythropoietic protoporphyrias, including autosomal recessive Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP) for clinical, biochemical, and genetic studies. The long-term objectives are (1) to conduct a longitudinal investigation of the natural history, complications, and therapeutic outcomes in people with erythropoietic protoporphyria, (2) to systematically investigate the psychological effects of the erythropoietic protoporphyrias on children and adults, and (3) to investigate the correlation between the identified genotypes and the resulting clinical presentation, also determining the possible interaction of other genetic markers.
Detailed description
The porphyrias are a group of rare metabolic diseases that may present in childhood or adult life and are due to deficiencies of enzymes in the heme biosynthetic pathway. The most common manifestations are related to accumulation of intermediates in the pathway and usually occur as acute neurological attacks (as in the acute or hepatic porphyrias), or cutaneous photosensitivity (as in the cutaneous porphyrias, including the erythropoietic protoporphyrias). Multiple mutations have been identified in each of the porphyrias. The risk of disability or death from these disorders is significant, in part because diagnosis is often delayed due to lack of adoption of diagnostic testing in clinical practice. Moreover, the natural history of these disorders is not well described and it is not known what determines differences in outcomes. New therapies are needed. For existing therapies, high-quality evidence on short and long term efficacy and safety is generally lacking. Therefore, the purpose of this study of a large group of patients with EPP and XLP is to provide a better understanding of the natural history of these disorders, as affected by available therapies, and to aid in developing new forms of treatment. Much of the data collected on subjects as participants in the Longitudinal Study of the Porphyrias will be accessed for this study specific to the investigation of the erythropoietic protoporphyrias. To maximize the information that can be informative in our objectives, additional data will be collected, including additional biochemical findings and EPP-specific psychosocial parameters.
The Office of Rare Diseases (ORD) of the National Institutes of Health (NIH) established a Rare Diseases Clinical Research Network (RDCRN) in collaboration with other NIH Institutes and currently has funded 19 rare diseases clinical research consortia and one Data Management and Coordinating Center. The Porphyrias Consortium was created as part of the RDCRN, to study the human porphyrias. The Porphyrias Consortium is a consortium of the academic institutions listed in the participating institutions table. All Centers in the Porphyrias Consortium are participating in this study. Additional centers may be added if funding is available.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants with Protoporphyrias | – | –Individuals with a documented diagnosis of Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP) |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Subjects will be recruited from the following resources: 1. Patients followed by one of the Investigators 2. The American Porphyria Foundation (APF) 3. The Rare Diseases Clinical Research Network (RDCRN) Contact Registry 4. Non-study Physician referrals 5. Self-referrals, including family members of individuals diagnosed with Porphyria (proband) and other individuals who may have heard about the study from other subjects or prospective subjects. 6. Medical Records Review
Key inclusion criteria (7 listed)
- All subjects must also be enrolled in the Longitudinal Study of the Porphyrias.
- Willing to sign informed consent form
- Biochemical findings - A marked increase in erythrocyte protoporphyrin [total erythrocyte protoporphyrin >200 ug/dL, or more than 1.5-fold increase (relative to ULN of 80 ug/dL)], with a predominance of free protoporphyrin (85-100% in EPP and 50-85% in XLP).
- Molecular findings - one of the following:
Key exclusion criteria (2 listed)
- cases with elevations of porphyrins in urine, plasma or erythrocytes due to other diseases (i.e. secondary porphyrinuria or porphyrinemia), such as liver and bone marrow diseases [Gibson 2000].
- patients with a prior diagnosis of porphyria that cannot be documented by review of existing medical records or repeat biochemical or DNA testing.
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
The Hospital Anxiety and Depression Scale (HADS)
Time frame: 1 weeks
Questionnaire with 7 items for anxiety and 7 items for depression, each item is scored on a 4 point response 0 - 3, subscales 0-21, with full range from 0 to 42, with higher score indicating more severe anxiety or depression.
Illness Perception Questionnaire Revised (IPQR)
Time frame: 1 week
Each item is scored on a likert scale from 1 (strongly disagree) to 5 (strongly agree). Items within each domain were totaled for final domain scores. Seven domains - Timeline (score 5-25), Consequences (score 6-30), Personal Control (score 6-30), Treatment Control (score 3-15), Illness Coherence (score 5-25), Timeline-Cyclical (score 4-20), and Emotional Representations (score 6-30). A modified version without the identity component was used as it was not applicable in EPP. Higher scores domains indicate overall strong beliefs that the disease is chronic and has a negative impact.
EPP-Specific Tool
Time frame: 1 week
Each item was scored from 0-3 on a Likert scale. There are 2 domains: S=disease severity and Q=QoL. Total scale for each domain transferred to 0-100 scale. Higher scores for the S domain reflect lower severity, and higher satisfaction/QoL for the Q domain. Total Score from 0-100, with higher score indicating higher quality of life.
1 secondary outcome
Sleep Disturbance PROMIS Scores
Time frame: baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Website for the Rare Diseases Clinical Research Network (RDCRN) Porphyrias Consortium (PC)Link provided by the sponsor.
Related trials for Erythropoietic Protoporphyria
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RecruitingPhase 2/3
A Study to Investigate PORT-77 Oral Dosing Compared With Placebo in Participants With Erythropoietic Protoporphyria (EPP) or X-linked Protoporphyria (XLP)
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EPP, XLP
RecruitingObservational study
Longitudinal Study of the Porphyrias
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Observational Study of Adults and Adolescents With Erythropoietic Protoporphyria (EPP) and X-linked Porphyria (XLP)
Erythropoietic Protoporphyria (EPP), X-Linked Porphyria (XLP)
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.
Manisha Balwani, MD principal investigator
Icahn School of Medicine at Mount Sinai
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 Erythropoietic Protoporphyria and EPP, run by Icahn School of Medicine at Mount Sinai 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?
The sponsor lists 7 inclusion and 2 exclusion criteria. 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 17 Apr 2020. 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?
Yes. Results are posted in the registry (first posted 17 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
The Hospital Anxiety and Depression Scale (HADS) (time frame: 1 weeks). The study lists 3 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 17 Apr 2020.