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

Pseudoxanthoma Elasticum Clinical Trial

— IMPROVE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03813550
• Other study ID #: 2018/79
• Status: Recruiting
• Phase: N/A
• Start date: January 21, 2019
• Est. completion date: January 30, 2020

Study information

• Verified date: January 2019
• Source: University Hospital, Angers
• Contact: Ludovic MARTIN, MD, PhD
• Phone: +332.41.35.55.76
• Email: LuMartin[@]chu-angers.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: January 30, 2020
• Est. primary completion date: January 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pseudoxanthoma Elasticum

Intervention

Diagnostic Test:
• Fecal and blood samples
Fecal samples for intestinal microbiota analysis; Blood and fecal samples for assessment of various forms of vitamin K

Locations

Country	Name	City	State
France	Department of Dermatology, University Hospital of Angers	Angers	Pays De Loire
France	Biofortis Mérieux NutriSciences	Saint-Herblain	Pays De La Loire
Netherlands	Department of Biochemistry, University Maastricht	Maastricht

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Angers	Biofortis Mérieux NutriSciences, Maastricht University

Countries where clinical trial is conducted

France,  Netherlands, 

References & Publications (39)

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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. — View Citation

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* Note: There are 39 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fecal samples for intestinal microbiota analysis	Gut microbiota composition and relative abundance of species (via metagenomic sequencing)	15 min
Primary	Fecal samples for assessment of various forms of vitamin K	Fecal Vitamin K species	15 min
Primary	Blood samples for assessment of various forms of vitamin K	Plasma Vitamin K species	15 min
Primary	Blood samples for assessment of dp-ucMGP	Plasma dp-ucMGP	15 min
Primary	Blood samples for assessment of PIVKA-II	Serum PIVKA-II	15 min
Primary	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	15 min