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

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ClinicalTrials.gov Identifier: NCT03813550
Recruitment Status : Unknown
Verified January 2019 by University Hospital, Angers.
Recruitment status was:  Recruiting
First Posted : January 23, 2019
Last Update Posted : February 4, 2019
Sponsor:
Collaborators:
Maastricht University
Biofortis Mérieux NutriSciences
Information provided by (Responsible Party):
University Hospital, Angers

Tracking Information
First Submitted Date  ICMJE January 19, 2019
First Posted Date  ICMJE January 23, 2019
Last Update Posted Date February 4, 2019
Actual Study Start Date  ICMJE January 21, 2019
Estimated Primary Completion Date January 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 31, 2019)
  • Fecal samples for intestinal microbiota analysis [ Time Frame: 15 min ]
    Gut microbiota composition and relative abundance of species (via metagenomic sequencing)
  • Fecal samples for assessment of various forms of vitamin K [ Time Frame: 15 min ]
    Fecal Vitamin K species
  • Blood samples for assessment of various forms of vitamin K [ Time Frame: 15 min ]
    Plasma Vitamin K species
  • Blood samples for assessment of dp-ucMGP [ Time Frame: 15 min ]
    Plasma dp-ucMGP
  • Blood samples for assessment of PIVKA-II [ Time Frame: 15 min ]
    Serum PIVKA-II
  • Severity of ocular and cardiovascular PXE manifestations and extent of PXE skin changes [ Time Frame: 15 min ]
    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
Original Primary Outcome Measures  ICMJE
 (submitted: January 19, 2019)
  • Fecal samples for intestinal microbiota analysis [ Time Frame: 15 min ]
    Gut microbiota composition and relative abundance of species (via metagenomic sequencing)
  • Blood and fecal samples for assessment of various forms of vitamin K [ Time Frame: 15 min ]
    Plasma and fecal Vitamin K species; plasma dp-ucMGP; serum PIVKA-II
  • Severity of ocular and cardiovascular PXE manifestations and extent of PXE skin changes [ Time Frame: 15 min ]
    Modified Phenodex score
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intestinal Microbiota and Vitamin K Levels in PXE Patients (IMPROVE Study)
Official Title  ICMJE Intestinal Microbiota and Vitamin K Levels in PXE Patients (IMPROVE Study)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Pseudoxanthoma Elasticum
Intervention  ICMJE Diagnostic Test: Fecal and blood samples
Fecal samples for intestinal microbiota analysis; Blood and fecal samples for assessment of various forms of vitamin K
Study Arms  ICMJE PXE cohort 2019-2020
PXE patient cohort monitored at referral centre from 2019 to 2020: fecal and blood samples
Intervention: Diagnostic Test: Fecal and blood samples
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: January 19, 2019)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 30, 2020
Estimated Primary Completion Date January 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03813550
Other Study ID Numbers  ICMJE 2018/79
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party University Hospital, Angers
Study Sponsor  ICMJE University Hospital, Angers
Collaborators  ICMJE
  • Maastricht University
  • Biofortis Mérieux NutriSciences
Investigators  ICMJE
Principal Investigator: Ludovic MARTIN, MD, PhD Department of Dermatology, University Hospital of Angers
PRS Account University Hospital, Angers
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP