Clinical trial NCT03813550: Intestinal Microbiota and Vitamin K Levels in PXE Patients (IMPROVE Study)
Official title: Intestinal Microbiota and Vitamin K Levels in PXE Patients (IMPROVE Study)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Pseudoxanthoma Elasticum
Keywords: PXE
calcification
Gla proteins
gut microbiota
vitamin K2
menaquinones
taxonomic meta-sequencing
Lead sponsor: University Hospital, Angers
Sponsor class: OTHER_GOV
Collaborators: name: Maastricht University
name: Biofortis Mérieux NutriSciences
First posted: 2019-01-23
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief 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).

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Fecal samples for intestinal microbiota analysis
timeFrame: 15 min
measure: Fecal samples for assessment of various forms of vitamin K
timeFrame: 15 min
measure: Blood samples for assessment of various forms of vitamin K
timeFrame: 15 min
measure: Blood samples for assessment of dp-ucMGP
timeFrame: 15 min
measure: Blood samples for assessment of PIVKA-II
timeFrame: 15 min
measure: Severity of ocular and cardiovascular PXE manifestations and extent of PXE skin changes
timeFrame: 15 min
Secondary outcomes:
Other outcomes:
Locations:
city: Saint-Herblain
country: France
facility: Biofortis Mérieux NutriSciences
state: Pays De La Loire
city: Angers
country: France
facility: Department of Dermatology, University Hospital of Angers
state: Pays De Loire
city: Maastricht
country: Netherlands
facility: Department of Biochemistry, University Maastricht
Study officials:
affiliation: Department of Dermatology, University Hospital of Angers
name: Ludovic MARTIN, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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