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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 : 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

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).

Condition or disease Intervention/treatment Phase
Pseudoxanthoma Elasticum Diagnostic Test: Fecal and blood samples Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Intestinal Microbiota and Vitamin K Levels in PXE Patients (IMPROVE Study)
Actual Study Start Date : January 21, 2019
Estimated Primary Completion Date : January 30, 2020
Estimated Study Completion Date : January 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vitamin K
Drug Information available for: Menadione

Arm Intervention/treatment
PXE cohort 2019-2020
PXE patient cohort monitored at referral centre from 2019 to 2020: fecal and blood samples
Diagnostic Test: Fecal and blood samples
Fecal samples for intestinal microbiota analysis; Blood and fecal samples for assessment of various forms of vitamin K




Primary Outcome Measures :
  1. Fecal samples for intestinal microbiota analysis [ Time Frame: 15 min ]
    Gut microbiota composition and relative abundance of species (via metagenomic sequencing)

  2. Fecal samples for assessment of various forms of vitamin K [ Time Frame: 15 min ]
    Fecal Vitamin K species

  3. Blood samples for assessment of various forms of vitamin K [ Time Frame: 15 min ]
    Plasma Vitamin K species

  4. Blood samples for assessment of dp-ucMGP [ Time Frame: 15 min ]
    Plasma dp-ucMGP

  5. Blood samples for assessment of PIVKA-II [ Time Frame: 15 min ]
    Serum PIVKA-II

  6. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03813550


Contacts
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Contact: Ludovic MARTIN, MD, PhD +332.41.35.55.76 LuMartin@chu-angers.fr

Locations
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France
Biofortis Mérieux NutriSciences Active, not recruiting
Saint-Herblain, Pays De La Loire, France, 44800
Department of Dermatology, University Hospital of Angers Recruiting
Angers, Pays De Loire, France, 49933
Contact: Ludovic Martin, MD, PhD    +332.41.35.55.76    LuMartin@chu-angers.fr   
Netherlands
Department of Biochemistry, University Maastricht Active, not recruiting
Maastricht, Netherlands, 6229
Sponsors and Collaborators
University Hospital, Angers
Maastricht University
Biofortis Mérieux NutriSciences
Investigators
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Principal Investigator: Ludovic MARTIN, MD, PhD Department of Dermatology, University Hospital of Angers

Publications:

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Responsible Party: University Hospital, Angers
ClinicalTrials.gov Identifier: NCT03813550     History of Changes
Other Study ID Numbers: 2018/79
First Posted: January 23, 2019    Key Record Dates
Last Update Posted: February 4, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Angers:
PXE
calcification
Gla proteins
gut microbiota
vitamin K2
menaquinones
taxonomic meta-sequencing
Additional relevant MeSH terms:
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Pseudoxanthoma Elasticum
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders
Hematologic Diseases
Skin Abnormalities
Congenital Abnormalities
Skin Diseases, Genetic
Genetic Diseases, Inborn
Connective Tissue Diseases
Skin Diseases
Vitamins
Vitamin K
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants