Pseudoxanthoma ElasticumPROPHECI-PPINCT04868578
PPI Supplementation to Fight ECtopIc Calcification in PXE
A study testing study treatment PPI in people with Pseudoxanthoma Elasticum, run by Centre Hospitalier Universitaire de Nice at 2 sites in France.
Trial summary
Pseudoxanthoma elasticum (PXE) is a rare inherited metabolic disorder (OMIM 264800, frequency 1/25000) characterized by progressive ectopic calcification of connective tissues. PXE mainly affects the skin (inesthetic papules and plaques in the skin folds), the retina (central blindness), the vasculature (peripheral… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Pseudoxanthoma Elasticum
- What is being tested?
- study treatment PPI
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 99 participants
- Where
- 2 sitesFrance
- Study dates
- 13 Dec 2022to 1 Sep 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients (>18 years and <65 years), men and women, presenting a clinically and biologically authenticated PXE (genotype + phenotype) according to the international diagnostic criteria (26).
- Efficient contraceptive method in woman of childbearing age at inclusion and during the overall study
- Patient affiliated to a social security insurance
- Signed informed consent
- Patient without acute complication linked or not to the pathology at the time of the study
- NON-INCLUSION CRITERIA
Show all 17Show fewer
- Renal insufficiency (i.e. defined by a renal clearance <30ml / min / 1.73 m²)
- Patients with osteomalacia
- Patients with chronic diarrhea (> 1 month)
- Pregnancy, lactating or fertile women who may wish to become pregnant within three years.
- Any other medical condition that may be considered in the opinion of the Principal Investigator.
- Use of bisphosphonate during last 5 years.
- Hypocalcemia (calcium <2.20 mmol/L and ionized calcium <1.15 mmol/L) *.
- Vitamin D deficiency <35 nmol/L *
- Enrollment in another inteventional clinical trial which could interfere with the present study
- patients (>18 years) protected by law
- After correcting the hypocalcemia and/or vitamin D deficiency, a participant is again suitable for participation in the trial, as long as the participant meets the inclusion criteria.
Who cannot join
None listed.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Sophie Bonnet contact
France2 sites, 2 recruiting
- Recruiting
Angers Hospital
Angers, 49000
ludovic Martin, PHD, 33 2 41 35 34 19, LuMartin@chu-angers.fr
ludovic Martin
- Recruiting
Nice Hospital
Nice, 06000
Georges leftheriotis, 04 92 03 29 41, leftheriotis.g@chu-nice.Fr
georges Leftheriotis
About this study
Official title: Efficacy of PyROphosPHate Supplementation to Fight ECtopIc Calcification in PseudoXanthoma Elasticum - PROPHECI-PPI Study
Pseudoxanthoma elasticum (PXE) is a rare inherited metabolic disorder (OMIM 264800, frequency 1/25000) characterized by progressive ectopic calcification of connective tissues. PXE mainly affects the skin (inesthetic papules and plaques in the skin folds), the retina (central blindness), the vasculature (peripheral arterial occlusive disease and stroke) and the renal system (renal lithiasis) in adulthood. Although rarely, early lethal forms have been reported. This chronic and highly disabling condition results from a loss of function of the gene encoding for the ABCC6 membrane transporter primarily expressed in the hepatocytes and renal tubular cells. Recently, it has been reported that PXE was characterized by a 50-60% decrease in the plasma level of inorganic pyrophosphate (PPi), a major physiological anti-calcifying factor. PXE is an incurable disease which therapeutic options are limited to symptomatic treatments to stem the devastating effect of the ectopic calcifications. Recently, encouraging proof of concept studies with animals PXE models and healthy volunteers have shown that, contrary to what was initially reported and thought, the oral administration of PPi salts are able to increase PPi plasma levels, opening up new therapeutic perspectives in PXE. Therefore, we propose to perform the first Phase II randomized controlled trial (RCT) to evaluate the safety and efficacy of a daily and oral administration of PPi salts against placebo in PXE patients.
- Conditions
- Pseudoxanthoma Elasticum
- Being tested
- study treatment PPI, Placebo comparator
- Medical subject headings
- Pseudoxanthoma Elasticum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
study treatment PPIDietary supplement
patient take PPI every day during 12 months
Placebo comparatorDietary supplement
patient take PPI placebo every day during 12 months
| Study group | Role | What they receive |
|---|---|---|
| PPI | Experimental | the patient take PPI caps Receives: Dietary Supplement: study treatment PPI |
| PPI placebo | Placebo comparator | The patient take PPI placebo Receives: Dietary Supplement: Placebo comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Arterial calcification score
Using manufacturer dedicated software, the investigator, will determine the calcification score from CT images according to the validated Agatston score method. A threshold of 130 Hounsfield Units for calcium detection will be used for the study. Voxels above this threshold representing arterial wall calcifications will be manually identified and selected by the observer on the CT image. Calcifications mass in the studied arterial segments will be analyzed and quantified. The length and antero-posterior mean diameter of each arterial segment will be determined for further normalization of the calcification score to the arterial wall surface (data expressed as HU/mm2 of arterial surface). The intraclass correlation and Bland-Altman coefficient for inter-observer reliability of the total peripheral artery calcium mass measurement will be determined by scoring 10 random scans by two independent investigators.
Measured: 12 months
Secondary outcomes (3)
clinical observation of dermatological changes
number of patient with dematological changes. Dermatological changes will be monitored by a dermatoscopic study of the skin according to the following protocol: Images will be acquired from commonly affected areas (neck, axilla, antecubital fossae, armpits and periumbilical area) by a contact dermatoscope (SD) with non-polarized light and recorded, as previously described .
The investigators will ensure that the very same areas are imaged at baseline and at the end of the study. The surface of SD elementary changes featuring yellow papulae (presenting as "dots" or "reticular networks") on digitized images will be compared using an open image processing software (ImageJ, https://imagej.nih.gov/ij/index.html NIH).
Measured: 12 months
clinical observation of ophtalmologic changes
Number of patietns with ophtalmologic changes. These changes will be monitored (blinded to treatment) by the occurrence of subretinal neovascularization events, the frequency of anti-VEGF administration and the best-corrected visual acuity (BCVA). A sub-retinal neovascularization event will be defined as any of the following that provide an indication to start or intensify anti-VEGF injections to prevent (further) visual impairment: 1) retinal bleeding suspected to be caused by sub-retinal neovascularization (if needed confirmed by fluorescein angiography); 2) a significant increase in sub retinal or intraretinal fluid; and/or 3) growth of a sub retinal neovascular complex. These events will be scored by the trained ophthalmologist of the PXE reference center (Dr Th Bresson) who will be blinded for the treatment.
Measured: 12 Montths
vascular changes
Ankle Brachial Index (ABI) at rest: Systolic arterial blood pressure will be recorded using a pneumatic cuff wrapped around the ankle. An ultrasound probe allows recording the blood flow in the left and right ankle arteries (namely posterior and anterior tibial arteries) and brachial arteries supine at rest. The ABI is determined by the ratio between the lowest ankle artery pressure and the highest brachial artery blood pressure.
A peripheral arterial occlusive disease (PAOD) is defined according to the actual recommendations: an ABI <0.90) and an incompressible arterial wall reflecting mediacalcosis defined by ABI>1.40.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2021
- Study start13 Dec 2022
- Primary completion13 Dec 2026 (estimated)
- Study completion1 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 99 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nice
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04868578
- Sponsor's protocol ID
- 19-APN-01
- Acronym
- PROPHECI-PPI
- Status last verified
- May 2024
- First submitted
- 30 Mar 2021
- Last updated
- 17 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Clotaire L, Rubera I, Duranton C, Gal J, Chamorey E, Humeau H, Yamani S, Chiaverini C, Willoteaux S, Padovani B, Mourozeau L, Mainguy A, Baillif S, Martin L, Leftheriotis G. The PROPHECI trial: a phase II, double-blind, placebo-controlled, randomized clinical trial for the treatment of pseudoxanthoma elasticum with oral pyrophosphate. Trials. 2025 Jan 29;26(1):30. doi: 10.1186/s13063-024-08666-w.
PubMed 39881395
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of PyROphosPHate Supplementation to Fight ECtopIc Calcification in PseudoXanthoma Elasticum - PROPHECI-PPI Study
- ClinicalTrials.gov ID
- NCT04868578
- Acronym / sponsor ID
- PROPHECI-PPI / 19-APN-01
- Conditions
- Pseudoxanthoma Elasticum
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 99 participants (estimated)
- Lead sponsor
- Centre Hospitalier Universitaire de NiceUniversity, hospital or other
- Study start
- 13 Dec 2022 (actual)
- Primary completion
- 13 Dec 2026 (estimated)
- Study completion
- 1 Sep 2027 (estimated)
- First posted
- 3 May 2021 (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.
Pseudoxanthoma elasticum (PXE) is a rare inherited metabolic disorder (OMIM 264800, frequency 1/25000) characterized by progressive ectopic calcification of connective tissues. PXE mainly affects the skin (inesthetic papules and plaques in the skin folds), the retina (central blindness), the vasculature (peripheral arterial occlusive disease and stroke) and the renal system (renal lithiasis) in adulthood. Although rarely, early lethal forms have been reported. This chronic and highly disabling condition results from a loss of function of the gene encoding for the ABCC6 membrane transporter primarily expressed in the hepatocytes and renal tubular cells. Recently, it has been reported that PXE was characterized by a 50-60% decrease in the plasma level of inorganic pyrophosphate (PPi), a major physiological anti-calcifying factor. PXE is an incurable disease which therapeutic options are limited to symptomatic treatments to stem the devastating effect of the ectopic calcifications. Recently, encouraging proof of concept studies with animals PXE models and healthy volunteers have shown that, contrary to what was initially reported and thought, the oral administration of PPi salts are able to increase PPi plasma levels, opening up new therapeutic perspectives in PXE. Therefore, we propose to perform the first Phase II randomized controlled trial (RCT) to evaluate the safety and efficacy of a daily and oral administration of PPi salts against placebo in PXE patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PPI | Experimental | Dietary Supplement: study treatment PPIthe patient take PPI caps |
| PPI placebo | Placebo comparator | Dietary Supplement: Placebo comparatorThe patient take PPI placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patients (>18 years and <65 years), men and women, presenting a clinically and biologically authenticated PXE (genotype + phenotype) according to the international diagnostic criteria (26).
- Efficient contraceptive method in woman of childbearing age at inclusion and during the overall study
- Patient affiliated to a social security insurance
- Signed informed consent
- Patient without acute complication linked or not to the pathology at the time of the study
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 |
|---|---|---|
| study treatment PPIpatient take PPI every day during 12 months | Dietary supplement | PPI |
| Placebo comparatorpatient take PPI placebo every day during 12 months | Dietary supplement | PPI placebo |
Primary outcome
Arterial calcification score
Time frame: 12 months
Using manufacturer dedicated software, the investigator, will determine the calcification score from CT images according to the validated Agatston score method. A threshold of 130 Hounsfield Units for calcium detection will be used for the study. Voxels above this threshold representing arterial wall calcifications will be manually identified and selected by the observer on the CT image. Calcifications mass in the studied arterial segments will be analyzed and quantified. The length and antero-posterior mean diameter of each arterial segment will be determined for further normalization of the calcification score to the arterial wall surface (data expressed as HU/mm2 of arterial surface). The intraclass correlation and Bland-Altman coefficient for inter-observer reliability of the total peripheral artery calcium mass measurement will be determined by scoring 10 random scans by two independent investigators.
3 secondary outcomes
clinical observation of dermatological changes
Time frame: 12 months
clinical observation of ophtalmologic changes
Time frame: 12 Montths
vascular changes
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2024.
- Derived from this study: PubMed 39881395Clotaire L, Rubera I, Duranton C, Gal J, Chamorey E, Humeau H, Yamani S, Chiaverini C, Willoteaux S, Padovani B, Mourozeau L, Mainguy A, Baillif S, Martin L, Leftheriotis G. The PROPHECI trial: a phase II, double-blind, placebo-controlled, randomized clinical trial for the treatment of pseudoxanthoma elasticum with oral pyrophosphate. Trials. 2025 Jan 29;26(1):30. doi: 10.1186/s13063-024-08666-w.
- Individual participant dataSharing planned: No
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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.
Sophie Bonnet contact
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing study treatment PPI in people with Pseudoxanthoma Elasticum, run by Centre Hospitalier Universitaire de Nice at 2 sites 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 17 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: looking for participants now, as of the sponsor's last update on 17 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. Some participants in this study may receive a placebo. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Georges LEFTHERIOTIS, PUPH (33 4 92 03 29 41, leftheriotis.g@chu-nice.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Arterial calcification score (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04868578, which also lists 1 linked publication.
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 May 2024.