Pseudoxanthoma ElasticumGOCAPXENCT03070860
What's Happen Under the Calcification Process in Pseudoxanthoma Elasticum
A study testing PET scan 18-FDG and 18-NAF in people with Pseudoxanthoma Elasticum, run by University Hospital, Angers at 1 site in France.
Trial summary
The investigators hypothesize is that in PXE patients, low grade chronic inflammation could preceed the molecular and the clinical calcification process. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pseudoxanthoma Elasticum
- What is being tested?
- PET scan 18-FDG and 18-NAF
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteFrance
- Study dates
- Nov 2016to Dec 2017
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- PXE patient diagnosed according the international criteria
- Informed consent obtained
- Patient affiliated to Health care system
- Exclusion criteria included inability or unwillingness to provide informed consent. Also, women of childbearing age not receiving contraception, pregnant women, nursing women, diabetic patients, patients with osteopenia, inflammatory or autoimmune systemic disease, high blood glucose concentrations (> 11 mmol/L) because of the competition between glucose and 18F-FDG for cellular entry.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Glucidic Metabolism, Ossification and Arterial Calcification During PseudoXanthoma Elasticum (PXE)
The investigators hypothesize is that in PXE patients, low grade chronic inflammation could preceed the molecular and the clinical calcification process.
Read the detailed description
Pseudoxanthoma elasticum (PXE; OMIM 264800), is an autosomal recessive metabolic disorder characterized by the fragmentation and progressive calcification of elastic fibers(elastorrhexis) in connective tissue in the skin, Bruch's membrane of the retina and the vascular system. PXE is caused by mutations in the ABCC6 (ATP-binding cassette subfamily C member 6) gene, located on the short arm of chromosome 16, encoding a transmembrane ATP binding anion transporter normally expressed in the liver and the kidney. The pathophysiology of PXE, particularly the mechanism of ectopic mineralization, remains largely unknown. PXE is currently an intractable disease, associated with considerable morbidity and occasional mortality due to cardiovascular complications. The major symptoms of the disease are characterized by unaesthetic skin folds, central blindness and cardiovascular complication with an early and severe peripheral arterial disease (PAD) and complication at younger age than the normal population. Unfortunately, histological studies are limited by the availability of arterial tissue from patients but it has been showed calcium deposition in the media layer of the large (i.e. aorta, carotids and femoral) and medium sized vessels (i.e. radial and ankle arteries) (ref). However, the underlying pathophysiology for arterial calcification in PXE remains incompletely defined, and there are currently no effective medical treatments capable of altering its course.
No longitudinal study has been performed to explain the calcification process in PXE. As PXE is a systemic metabolic disease, low grade inflammation could be the trigger of a deregulated inflammation resolution process resulted in calcification. Thus, alternative techniques are therefore required to investigate the pathogenesis and progression of this condition.
Positron emission tomography (PET) combined with computed tomography (CT) is a noninvasive imaging technique that allows the identification and quantification of specific biochemical processes within small anatomic structures, such as vascular wall. Furthermore, 2 common PET tracers target calcification and inflammation, which are believed to play a key role in the development of the disease. 18F Flurodeoxyglucose (18F-FDG) is a glucose analogue that is taken up into cells by glucose transport proteins and enters the glycolytic metabolic pathway. After the initial hexokinase step, 18F-FDG-6-phosphate cannot be metabolized further and becomes trapped within cells that have high metabolic requirements, such as macrophages. PET imaging with the use of 18F-FDG has become an established means of quantifying vascular inflammation in both the aorta and carotid arteries, correlating with plaque macrophage burden and symptomatic status. 18F-Sodium fluoride (18FNaF) is an alternative PET tracer that is directly incorporated into exposed bone crystal (hydroxyapatite) via an exchange mechanism with hydroxyl groups. It is therefore thought to detect areas of novel calcification and regions of calcium remodeling and is used clinically for the detection of primary osteoblastic tumors and bone metastases. More recently, studies have described 18F-NaF uptake as a marker of calcification within atherosclerotic plaque. More recently, the calcifying process was examined in 4 PXE patients using 18NaF PET/CT showing in the femoral arteries, increased arterial wall 18NaF signal at levels similar to those for cortical bone. However, the mechanism responsible for the increased osteoblastic activity leading to arterial wall calcification in PXE remains unknown.
.
In this study, the investigators investigated 18F-NaF and 18F-FDG uptake in the arterial wall and skin of patients with PXE with 3 major aims: :
- Does low grade inflammation in vascular wall and skin exist in PXE patient and a specificity site might exist?
- Does low grade inflammation in vascular wall and skin quantified by 18F-FDG preceed the molecular calcification process quantified by 18F-NaF?
- Does low grade inflammation and bone turn over correlate conversely to calcium score?
- Conditions
- Pseudoxanthoma Elasticum
- Being tested
- PET scan 18-FDG and 18-NAF
- Keywords
- Low Grade Chronic vascular and skin Inflammation, Molecular vascular and skin Calcification, Calcium Score
- Medical subject headings
- Pseudoxanthoma Elasticum, Dermatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PET scan 18-FDG and 18-NAFRadiation
Also called positron emission tomography
Positron emission tomography (PET) is a medical imaging test performed in a nuclear medicine department.
PET scan is performed by IV injection of a mildly radioactive tracer (NAF and FDG).
| Study group | Role | What they receive |
|---|---|---|
| PXE Patient | Experimental | positron emission tomography scanner (PET scan) 18-FDG and 18-NAF: conventionnal use. Receives: Radiation: PET scan 18-FDG and 18-NAF |
What is being measured
The primary outcome is the main question the study is designed to answer.
Vascular Inflammation
Measurement 18F-FDG TBRs of patients with PXE; and the comparison of 18F-NaF femoral arteries' TBRs with popliteal artery's TBRs of patients with PXE (at 30 min and 90min post injection).
Measured: 90min post injection : 1 time
Molecular Calcification
Measurement 18F-NaF femoral arteries' TBRs with popliteal artery's TBRs of patients with PXE
Measured: 90min post injection : 1 time
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2017
- Study startNov 2016
- Primary completionDec 2017
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pseudoxanthoma ElasticumStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Angers
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Loukman OMARJEE, MD,MSc, Principal investigator, University Hospital, Angers
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03070860
- Sponsor's protocol ID
- 2014-A01614-43
- Acronym
- GOCAPXE
- Status last verified
- Jun 2018
- First submitted
- 13 Jun 2016
- Last updated
- 28 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glucidic Metabolism, Ossification and Arterial Calcification During PseudoXanthoma Elasticum (PXE)
- ClinicalTrials.gov ID
- NCT03070860
- Acronym / sponsor ID
- GOCAPXE / 2014-A01614-43
- Conditions
- Pseudoxanthoma Elasticum
- Keywords
- Low Grade Chronic vascular and skin Inflammation, Molecular vascular and skin Calcification, Calcium Score
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- University Hospital, AngersOther government
- Study start
- Nov 2016 (actual)
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 6 Mar 2017 (actual)
- 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 investigators hypothesize is that in PXE patients, low grade chronic inflammation could preceed the molecular and the clinical calcification process.
Detailed description
Pseudoxanthoma elasticum (PXE; OMIM 264800), is an autosomal recessive metabolic disorder characterized by the fragmentation and progressive calcification of elastic fibers(elastorrhexis) in connective tissue in the skin, Bruch's membrane of the retina and the vascular system. PXE is caused by mutations in the ABCC6 (ATP-binding cassette subfamily C member 6) gene, located on the short arm of chromosome 16, encoding a transmembrane ATP binding anion transporter normally expressed in the liver and the kidney. The pathophysiology of PXE, particularly the mechanism of ectopic mineralization, remains largely unknown. PXE is currently an intractable disease, associated with considerable morbidity and occasional mortality due to cardiovascular complications. The major symptoms of the disease are characterized by unaesthetic skin folds, central blindness and cardiovascular complication with an early and severe peripheral arterial disease (PAD) and complication at younger age than the normal population. Unfortunately, histological studies are limited by the availability of arterial tissue from patients but it has been showed calcium deposition in the media layer of the large (i.e. aorta, carotids and femoral) and medium sized vessels (i.e. radial and ankle arteries) (ref). However, the underlying pathophysiology for arterial calcification in PXE remains incompletely defined, and there are currently no effective medical treatments capable of altering its course.
No longitudinal study has been performed to explain the calcification process in PXE. As PXE is a systemic metabolic disease, low grade inflammation could be the trigger of a deregulated inflammation resolution process resulted in calcification. Thus, alternative techniques are therefore required to investigate the pathogenesis and progression of this condition.
Positron emission tomography (PET) combined with computed tomography (CT) is a noninvasive imaging technique that allows the identification and quantification of specific biochemical processes within small anatomic structures, such as vascular wall. Furthermore, 2 common PET tracers target calcification and inflammation, which are believed to play a key role in the development of the disease. 18F Flurodeoxyglucose (18F-FDG) is a glucose analogue that is taken up into cells by glucose transport proteins and enters the glycolytic metabolic pathway. After the initial hexokinase step, 18F-FDG-6-phosphate cannot be metabolized further and becomes trapped within cells that have high metabolic requirements, such as macrophages. PET imaging with the use of 18F-FDG has become an established means of quantifying vascular inflammation in both the aorta and carotid arteries, correlating with plaque macrophage burden and symptomatic status. 18F-Sodium fluoride (18FNaF) is an alternative PET tracer that is directly incorporated into exposed bone crystal (hydroxyapatite) via an exchange mechanism with hydroxyl groups. It is therefore thought to detect areas of novel calcification and regions of calcium remodeling and is used clinically for the detection of primary osteoblastic tumors and bone metastases. More recently, studies have described 18F-NaF uptake as a marker of calcification within atherosclerotic plaque. More recently, the calcifying process was examined in 4 PXE patients using 18NaF PET/CT showing in the femoral arteries, increased arterial wall 18NaF signal at levels similar to those for cortical bone. However, the mechanism responsible for the increased osteoblastic activity leading to arterial wall calcification in PXE remains unknown.
.
In this study, the investigators investigated 18F-NaF and 18F-FDG uptake in the arterial wall and skin of patients with PXE with 3 major aims: :
- Does low grade inflammation in vascular wall and skin exist in PXE patient and a specificity site might exist?
- Does low grade inflammation in vascular wall and skin quantified by 18F-FDG preceed the molecular calcification process quantified by 18F-NaF?
- Does low grade inflammation and bone turn over correlate conversely to calcium score?
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PXE Patient | Experimental | Radiation: PET scan 18-FDG and 18-NAFpositron emission tomography scanner (PET scan) 18-FDG and 18-NAF: conventionnal use. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- PXE patient diagnosed according the international criteria
- Informed consent obtained
- Patient affiliated to Health care system
- Exclusion criteria included inability or unwillingness to provide informed consent. Also, women of childbearing age not receiving contraception, pregnant women, nursing women, diabetic patients, patients with osteopenia, inflammatory or autoimmune systemic disease, high blood glucose concentrations (> 11 mmol/L) because of the competition between glucose and 18F-FDG for cellular entry.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PET scan 18-FDG and 18-NAFAlso: positron emission tomographyPositron emission tomography (PET) is a medical imaging test performed in a nuclear medicine department. PET scan is performed by IV injection of a mildly radioactive tracer (NAF and FDG). | Radiation | PXE Patient |
Primary outcome
Vascular Inflammation
Time frame: 90min post injection : 1 time
Measurement 18F-FDG TBRs of patients with PXE; and the comparison of 18F-NaF femoral arteries' TBRs with popliteal artery's TBRs of patients with PXE (at 30 min and 90min post injection).
Molecular Calcification
Time frame: 90min post injection : 1 time
Measurement 18F-NaF femoral arteries' TBRs with popliteal artery's TBRs of patients with PXE
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 Jun 2018.
- Individual participant dataSharing planned: Undecided
Related trials for Pseudoxanthoma Elasticum
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CHOPXE - Analysis of Choriocapillaris Flow Deficits in Patients With Pseudoxanthoma Elasticum
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Progression Assessment of PXE-associated Alterations
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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.
Loukman OMARJEE, MD,MSc principal investigator
University Hospital, Angers
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PET scan 18-FDG and 18-NAF in people with Pseudoxanthoma Elasticum, run by University Hospital, Angers at 1 site in France.
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 4 inclusion and 0 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 28 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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?
Vascular Inflammation (time frame: 90min post injection : 1 time). The study lists 2 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 Jun 2018.