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

Primary Purpose

Pseudoxanthoma Elasticum

Status
Unknown status
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Fecal and blood samples
Sponsored by
University Hospital, Angers
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Pseudoxanthoma Elasticum focused on measuring PXE, calcification, Gla proteins, gut microbiota, vitamin K2, menaquinones, taxonomic meta-sequencing

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Biofortis Mérieux NutriSciences
  • Department of Dermatology, University Hospital of AngersRecruiting
  • Department of Biochemistry, University Maastricht

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

PXE cohort 2019-2020

Arm Description

PXE patient cohort monitored at referral centre from 2019 to 2020: fecal and blood samples

Outcomes

Primary Outcome Measures

Fecal samples for intestinal microbiota analysis
Gut microbiota composition and relative abundance of species (via metagenomic sequencing)
Fecal samples for assessment of various forms of vitamin K
Fecal Vitamin K species
Blood samples for assessment of various forms of vitamin K
Plasma Vitamin K species
Blood samples for assessment of dp-ucMGP
Plasma dp-ucMGP
Blood samples for assessment of PIVKA-II
Serum PIVKA-II
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

Secondary Outcome Measures

Full Information

First Posted
January 19, 2019
Last Updated
January 31, 2019
Sponsor
University Hospital, Angers
Collaborators
Maastricht University, Biofortis Mérieux NutriSciences
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1. Study Identification

Unique Protocol Identification Number
NCT03813550
Brief Title
Intestinal Microbiota and Vitamin K Levels in PXE Patients (IMPROVE Study)
Acronym
IMPROVE
Official Title
Intestinal Microbiota and Vitamin K Levels in PXE Patients (IMPROVE Study)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Unknown status
Study Start Date
January 21, 2019 (Actual)
Primary Completion Date
January 30, 2020 (Anticipated)
Study Completion Date
January 30, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Angers
Collaborators
Maastricht University, Biofortis Mérieux NutriSciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pseudoxanthoma Elasticum
Keywords
PXE, calcification, Gla proteins, gut microbiota, vitamin K2, menaquinones, taxonomic meta-sequencing

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PXE cohort 2019-2020
Arm Type
Other
Arm Description
PXE patient cohort monitored at referral centre from 2019 to 2020: fecal and blood samples
Intervention Type
Diagnostic Test
Intervention Name(s)
Fecal and blood samples
Intervention Description
Fecal samples for intestinal microbiota analysis; Blood and fecal samples for assessment of various forms of vitamin K
Primary Outcome Measure Information:
Title
Fecal samples for intestinal microbiota analysis
Description
Gut microbiota composition and relative abundance of species (via metagenomic sequencing)
Time Frame
15 min
Title
Fecal samples for assessment of various forms of vitamin K
Description
Fecal Vitamin K species
Time Frame
15 min
Title
Blood samples for assessment of various forms of vitamin K
Description
Plasma Vitamin K species
Time Frame
15 min
Title
Blood samples for assessment of dp-ucMGP
Description
Plasma dp-ucMGP
Time Frame
15 min
Title
Blood samples for assessment of PIVKA-II
Description
Serum PIVKA-II
Time Frame
15 min
Title
Severity of ocular and cardiovascular PXE manifestations and extent of PXE skin changes
Description
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
Time Frame
15 min

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ludovic MARTIN, MD, PhD
Phone
+332.41.35.55.76
Email
LuMartin@chu-angers.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ludovic MARTIN, MD, PhD
Organizational Affiliation
Department of Dermatology, University Hospital of Angers
Official's Role
Principal Investigator
Facility Information:
Facility Name
Biofortis Mérieux NutriSciences
City
Saint-Herblain
State/Province
Pays De La Loire
ZIP/Postal Code
44800
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Department of Dermatology, University Hospital of Angers
City
Angers
State/Province
Pays De Loire
ZIP/Postal Code
49933
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ludovic Martin, MD, PhD
Phone
+332.41.35.55.76
Email
LuMartin@chu-angers.fr
Facility Name
Department of Biochemistry, University Maastricht
City
Maastricht
ZIP/Postal Code
6229
Country
Netherlands
Individual Site Status
Active, not recruiting

12. IPD Sharing Statement

Plan to Share IPD
Undecided
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Intestinal Microbiota and Vitamin K Levels in PXE Patients (IMPROVE Study)

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