AzTrials
AzTrials

Pseudoxanthoma ElasticumIMPROVENCT03813550

Intestinal Microbiota and Vitamin K Levels in PXE Patients (IMPROVE Study)

A study testing Fecal and blood samples in people with Pseudoxanthoma Elasticum, run by University Hospital, Angers at 3 sites in 2 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

This study aims to demonstrate a potential association between gut microbiota composition, plasma levels of various forms of vitamin K, and severity of clinical manifestations of Pseudoxanthoma Elasticum (PXE). 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?
Fecal and blood samples
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
3 sitesin 2 countries
Study dates
21 Jan 2019to 30 Jan 2020
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

  • Patients with phenotypically and genetically (ABCC6) proven PXE
  • Aged over 18 years
  • Written consent obtained for Angers University Hospital (France) PXE bio-collection

Who cannot join

  • Patients under the age of 18
  • Patients unwilling to participate in the study, or unable to sign the bio-collection consent form

Trial locations and contacts

3 sites in 2 countries.

Ludovic MARTIN, MD, PhD contact

+332.41.35.55.76

LuMartin@chu-angers.fr

3 sites in 2 countries

France2 sites, 1 recruiting

  • Department of Dermatology, University Hospital of Angers

    Angers, Pays de Loire, 49933

    Ludovic Martin, MD, PhD, +332.41.35.55.76, LuMartin@chu-angers.fr

    Recruiting

  • Biofortis Mérieux NutriSciences

    Saint-Herblain, Pays de la Loire Region, 44800

    Active, not recruiting

Other trials in France

Netherlands1 site

  • Department of Biochemistry, University Maastricht

    Maastricht, 6229

    Active, not recruiting

Other trials in Netherlands

About this study

This study aims to demonstrate a potential association between gut microbiota composition, plasma levels of various forms of vitamin K, and severity of clinical manifestations of Pseudoxanthoma Elasticum (PXE).

Read the detailed description

Vitamin K deficiency contributes to pathological calcification which underlies the clinical picture of pseudoxanthoma elasticum (PXE), an inherited autosomal recessive disease. A substantial proportion of vitamin K, namely the K2 form (menaquinones), is produced by gut microbiota. In healthy volunteers fecal levels of the major menaquinone producers, Escherichia coli and Bacteroides species, are approximately 5 and 9 log10 CFU/g dry weight respectively. There is however a lack of data on gut microbiota in PXE patients. The objective of our project is to demonstrate a potential association between gut microbiota composition, plasma levels of various forms of vitamin K and severity of clinical manifestations in PXE patients.

This study will be performed as Research surrounding bio collection "Clinical and biological exploration of PXE patients" kept at the Center of Biological Resources of Angers University Hospital (bio collection n° DC 20116-14-67, authorization to transfer n° 2016-27-99). Fecal samples, plasma samples and clinical data will be collected from patients diagnosed with PXE who will be monitored at the Angers University Hospital Referral Center (France) in 2019-2020. Clinical severity of PXE will be assessed using modified Phenodex score. Gut microbiota will be analyzed using metagenomic sequencing. Plasma Vitamin K species and fecal excretion of menaquinones will be assessed using HPLC. Plasma dp-ucMGP (circulating biomarker of vitamin K status) and serum PIVKA-II (protein induced by vitamin K absence-II) will be assessed using immunoassay. Results will be compared to healthy age- and gender-matched controls from the pre-existing Biofortis database.

Being tested
Fecal and blood samples
Keywords
PXE, calcification, Gla proteins, gut microbiota, vitamin K2, menaquinones, taxonomic meta-sequencing
Medical subject headings
Pseudoxanthoma Elasticum, Calcinosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Fecal and blood samplesDiagnostic test

    Fecal samples for intestinal microbiota analysis; Blood and fecal samples for assessment of various forms of vitamin K

Study groups in NCT03813550
Study groupRoleWhat they receive
PXE cohort 2019-2020OtherPXE patient cohort monitored at referral centre from 2019 to 2020: fecal and blood samples
Receives: Diagnostic Test: Fecal and blood samples

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Fecal samples for intestinal microbiota analysis

    Gut microbiota composition and relative abundance of species (via metagenomic sequencing)

    Measured: 15 min

  2. Fecal samples for assessment of various forms of vitamin K

    Fecal Vitamin K species

    Measured: 15 min

  3. Blood samples for assessment of various forms of vitamin K

    Plasma Vitamin K species

    Measured: 15 min

  4. Blood samples for assessment of dp-ucMGP

    Plasma dp-ucMGP

    Measured: 15 min

  5. Blood samples for assessment of PIVKA-II

    Serum PIVKA-II

    Measured: 15 min

  6. Severity of ocular and cardiovascular PXE manifestations and extent of PXE skin changes

    Modified Phenodex score:

    • Skin lesions severity: S0=No sign; S1= Papules/bumps; S2= Plaques of coalesced papules; S3= Lax and redundant skin
    • Number of affected skin sites: for Typical and Nontypical areas
    • Ophthalmological involvement: E0= No sign; E1= Peau d'orange ; E2= Angioid streaks; E3a=Medical history of bleeding and/or scarring; E3b= Unilateral or bilateral blindness
    • Gastrointestinal bleeding: G0= No sign; G1= Gastrointestinal bleeding as related to PXE
    • Vascular involvement: V0= No sign; V1= Weak or absent pulse or peripheral artery disease revealed by vascular imaging; V2= Intermittent claudication; V3= Medical history of vascular surgery or Stroke/TIA
    • Cardiac involvement: C0= No sign; C1= medical history of chest pain/angina/abnormal EKG or abnormal stress test with no symptom, or Mitral insufficiency; C2= Heart attack
    • Renal involvement: R0= No sign; R1a= asymptomatic nephrocalcinosis revealed by imaging; R1b= Nephrolithiasis

    Measured: 15 min

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jan 2019
  2. Study start21 Jan 2019
  3. Primary completion30 Jan 2020 (estimated)
  4. Study completion30 Jan 2020 (estimated)

Resources

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
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03813550
Sponsor's protocol ID
2018/79
Acronym
IMPROVE
Status last verified
Jan 2019
First submitted
19 Jan 2019
Last updated
4 Feb 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Jansen RS, Duijst S, Mahakena S, Sommer D, Szeri F, Varadi A, Plomp A, Bergen AA, Oude Elferink RP, Borst P, van de Wetering K. ABCC6-mediated ATP secretion by the liver is the main source of the mineralization inhibitor inorganic pyrophosphate in the systemic circulation-brief report. Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):1985-9. doi: 10.1161/ATVBAHA.114.304017. Epub 2014 Jun 26.

    PubMed 24969777

  • Jansen RS, Kucukosmanoglu A, de Haas M, Sapthu S, Otero JA, Hegman IE, Bergen AA, Gorgels TG, Borst P, van de Wetering K. ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release. Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20206-11. doi: 10.1073/pnas.1319582110. Epub 2013 Nov 25.

    PubMed 24277820

  • Pomozi V, Brampton C, van de Wetering K, Zoll J, Calio B, Pham K, Owens JB, Marh J, Moisyadi S, Varadi A, Martin L, Bauer C, Erdmann J, Aherrahrou Z, Le Saux O. Pyrophosphate Supplementation Prevents Chronic and Acute Calcification in ABCC6-Deficient Mice. Am J Pathol. 2017 Jun;187(6):1258-1272. doi: 10.1016/j.ajpath.2017.02.009. Epub 2017 Apr 14.

    PubMed 28416300

  • Gheduzzi D, Boraldi F, Annovi G, DeVincenzi CP, Schurgers LJ, Vermeer C, Quaglino D, Ronchetti IP. Matrix Gla protein is involved in elastic fiber calcification in the dermis of pseudoxanthoma elasticum patients. Lab Invest. 2007 Oct;87(10):998-1008. doi: 10.1038/labinvest.3700667. Epub 2007 Aug 27.

    PubMed 17724449

  • Hendig D, Zarbock R, Szliska C, Kleesiek K, Gotting C. The local calcification inhibitor matrix Gla protein in pseudoxanthoma elasticum. Clin Biochem. 2008 Apr;41(6):407-12. doi: 10.1016/j.clinbiochem.2007.12.023. Epub 2008 Jan 11.

    PubMed 18222176

  • Li Q, Jiang Q, Schurgers LJ, Uitto J. Pseudoxanthoma elasticum: reduced gamma-glutamyl carboxylation of matrix gla protein in a mouse model (Abcc6-/-). Biochem Biophys Res Commun. 2007 Dec 14;364(2):208-13. doi: 10.1016/j.bbrc.2007.09.122. Epub 2007 Oct 4.

    PubMed 17942075

  • Vanakker OM, Martin L, Schurgers LJ, Quaglino D, Costrop L, Vermeer C, Pasquali-Ronchetti I, Coucke PJ, De Paepe A. Low serum vitamin K in PXE results in defective carboxylation of mineralization inhibitors similar to the GGCX mutations in the PXE-like syndrome. Lab Invest. 2010 Jun;90(6):895-905. doi: 10.1038/labinvest.2010.68. Epub 2010 Apr 5.

    PubMed 20368697

  • Gorgels TG, Waarsing JH, Herfs M, Versteeg D, Schoensiegel F, Sato T, Schlingemann RO, Ivandic B, Vermeer C, Schurgers LJ, Bergen AA. Vitamin K supplementation increases vitamin K tissue levels but fails to counteract ectopic calcification in a mouse model for pseudoxanthoma elasticum. J Mol Med (Berl). 2011 Nov;89(11):1125-35. doi: 10.1007/s00109-011-0782-y. Epub 2011 Jul 2.

    PubMed 21725681

  • Shearer MJ, Bach A, Kohlmeier M. Chemistry, nutritional sources, tissue distribution and metabolism of vitamin K with special reference to bone health. J Nutr. 1996 Apr;126(4 Suppl):1181S-6S. doi: 10.1093/jn/126.suppl_4.1181S.

    PubMed 8642453

  • Ramotar K, Conly JM, Chubb H, Louie TJ. Production of menaquinones by intestinal anaerobes. J Infect Dis. 1984 Aug;150(2):213-8. doi: 10.1093/infdis/150.2.213.

    PubMed 6470528

  • Shearer MJ. Vitamin K. Lancet. 1995 Jan 28;345(8944):229-34. doi: 10.1016/s0140-6736(95)90227-9. No abstract available.

    PubMed 7823718

  • Walther B, Karl JP, Booth SL, Boyaval P. Menaquinones, bacteria, and the food supply: the relevance of dairy and fermented food products to vitamin K requirements. Adv Nutr. 2013 Jul 1;4(4):463-73. doi: 10.3945/an.113.003855.

    PubMed 23858094

  • Bentley R, Meganathan R. Biosynthesis of vitamin K (menaquinone) in bacteria. Microbiol Rev. 1982 Sep;46(3):241-80. doi: 10.1128/mr.46.3.241-280.1982. No abstract available.

    PubMed 6127606

  • Conly JM, Stein K. The production of menaquinones (vitamin K2) by intestinal bacteria and their role in maintaining coagulation homeostasis. Prog Food Nutr Sci. 1992 Oct-Dec;16(4):307-43.

    PubMed 1492156

  • Beulens JW, Booth SL, van den Heuvel EG, Stoecklin E, Baka A, Vermeer C. The role of menaquinones (vitamin K(2)) in human health. Br J Nutr. 2013 Oct;110(8):1357-68. doi: 10.1017/S0007114513001013. Epub 2013 Apr 16.

    PubMed 23590754

Questions about this trial

What is this clinical trial studying?

A study testing Fecal and blood samples in people with Pseudoxanthoma Elasticum, run by University Hospital, Angers at 3 sites in 2 countries.

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 3 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: status not confirmed, as of the sponsor's last update on 4 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in France, Netherlands. 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Ludovic MARTIN, MD, PhD (+332.41.35.55.76, LuMartin@chu-angers.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Fecal samples for intestinal microbiota analysis (time frame: 15 min). The study lists 6 primary outcomes in all. 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 NCT03813550, which also lists 39 linked publications.

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 4 Feb 2019; AzTrials last refreshed its copy on 8 Nov 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in