Evaluation of the Intestinal Microbiota and Bacterial Translocation in Patients With DR4 Homozygous Rheumatoid Arthritis (MICROPOLY)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified March 2014 by Centre Hospitalier Universitaire de Nīmes
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nīmes
ClinicalTrials.gov Identifier:
NCT01961310
First received: October 9, 2013
Last updated: March 3, 2014
Last verified: March 2014
  Purpose

The main objective of this study is to compare the intestinal microbiota in newly diagnosed patients with homozygous DR4 rheumatoid arthritis (RA)with that from DR4 homozygous individuals without RA.

The first analysis will compare the proportion of filamentous bacteria in the intestinal microbiota between the two groups.


Condition Intervention
Arthritis, Rheumatoid
Biological: Plasma analysis for bacterial translocation
Biological: Stool analysis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Evaluation of the Intestinal Microbiota and Bacterial Translocation in Patients With DR4 Homozygous Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire de Nīmes:

Primary Outcome Measures:
  • The proportion of filamentous bacteria in the intestinal microbiota [ Time Frame: Baseline (day 0) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The proportion of Proteus mirabilis in the intestinal microbiota [ Time Frame: baseline (Day 0) ] [ Designated as safety issue: No ]
  • The proportion of species producing peptidyl arginine desaminase (PAD) in the intestinal microbiota [ Time Frame: baseline (Day 0) ] [ Designated as safety issue: No ]
  • The number of species found in the intestinal microbiota [ Time Frame: baseline (Day 0) ] [ Designated as safety issue: No ]
  • Presence/absence of bacterial translocation [ Time Frame: baseline (Day 0) ] [ Designated as safety issue: No ]
  • Description of the ecology of intestinal microbiota [ Time Frame: baseline (Day 0) ] [ Designated as safety issue: No ]
    Diversity indices according to species and/or functional groups. The general goal is to provide a description of the functional differences between groups.


Estimated Enrollment: 50
Study Start Date: September 2014
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
DR4 homozygous RA

This group is composed of 25 patients with RA and who are homozygous for the HLA-DR4 allele. The diagnosis of RA is based upon the American College of Rheumatology criteria.

  • Intervention: Plasma analysis for bacterial translocation
  • Intervention: Stool analysis
Biological: Plasma analysis for bacterial translocation
1 ml of plasma will be obtained (blood sample). DNA will be extracted and amplified, and real-time quantitative PCR (polymerase chain reaction) performed.
Biological: Stool analysis
DNA from stool samples will be extracted, amplified, and used to identify the bacteria species present.
DR4 homozygous volunteer

This group is composed of 25 healthy volunteers who are homozygous for the HLA-DR4 allele and who do not have RA.

  • Intervention: Plasma analysis for bacterial translocation
  • Intervention: Stool analysis
Biological: Plasma analysis for bacterial translocation
1 ml of plasma will be obtained (blood sample). DNA will be extracted and amplified, and real-time quantitative PCR (polymerase chain reaction) performed.
Biological: Stool analysis
DNA from stool samples will be extracted, amplified, and used to identify the bacteria species present.

Detailed Description:

The secondary objectives of this study are :

  • A. To compare between the two groups :
  • a. The proportion of Proteus mirabilis in the intestinal microbiota
  • b . The proportion of species producing peptidyl arginine deaminase (PAD ) in the intestinal microbiota
  • c . The number of species found in the intestinal microbiota
  • B. To evaluate bacterial translocation (from the digestive tract) in patients with newly diagnosed, homozygous DR4 RA and homozygous DR4 healthy volunteers without RA. (Bacterial translocation is a phenomenon in which live bacteria or a part of bacteria (e.g. LPS teichoïc acid) cross the intestinal barrier and reach the bloodstream.)
  • C. To describe the ecology of the intestinal microbiota of patients with homozygous DR4 RA (characterization of species found according to their respiratory metabolism, according to their bacteriological characteristics, and according to wether or not the species are found significantly more frequently in patients with RA than in individuals without RA).
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

A total of 50 adult subjects will be included: 25 with newly diagnosed RA (<12 months) based on the American College of Rheumatology criteria, and 25 healthy volunteers without RA.

All subjects are homozygous for the HLA-DR4 allele.

Criteria

Inclusion Criteria for RA patients:

  • The patient was correctly informed
  • The patient must have given his/her informed and signed consent
  • The patient must be insured or beneficiary of a health insurance plan
  • Homozygous for the HLA-DR4 allele
  • No antibiotic treatments within the 30 days preceding inclusion
  • RA diagnosis made within the past 12 months

Exclusion Criteria for RA patients:

  • The patient has participated in another study within the past 3 months
  • The patient is under judicial protection, or any kind of guardianship
  • The patient refuses to sign the consent
  • It is impossible to correctly inform the patient
  • The patient is pregnant, parturient, or breastfeeding
  • The patient is not homozygous for the HLA-DR4 allele
  • The patient has taken antibiotics in the 30 days preceding inclusion
  • RA was diagnosed more than 12 months ago

Inclusion Criteria for healthy volunteers (HV):

  • The HV was correctly informed
  • The HV must have given his/her informed and signed consent
  • The HV must be insured or beneficiary of a health insurance plan
  • Homozygous for the HLA-DR4 allele
  • No antibiotic treatments within the 30 days preceding inclusion
  • Does not have RA

Exclusion Criteria for HVs:

  • The HV has participated in another study within the past 3 months
  • The HV is under judicial protection, or any kind of guardianship
  • The HV refuses to sign the consent
  • It is impossible to correctly inform the HV
  • The HV is pregnant, parturient, or breastfeeding
  • The HV is not homozygous for the HLA-DR4 allele
  • The HV has taken antibiotics in the 30 days preceding inclusion
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01961310

Contacts
Contact: Catherine Dunyach-Remy, PharmD, PhD +33.(0)4.66.02.81.49 dunyachcatherine@yahoo.fr
Contact: Carey Suehs, PhD +33.(0)4.66.68.67.88 carey.suehs@chu-nimes.fr

Locations
France
CHRU de Montpellier - Hôpital Lapeyronie Not yet recruiting
Montpellier, France, 34295
Principal Investigator: Christian Jorgensen, MD, PhD         
Sub-Investigator: Yves Marie Pers, MD         
Sub-Investigator: Pierre Le Blay, MD         
Sub-Investigator: Rosanna Ferreira, MD         
Unité U1047 "Bacterial virulence and infectious diseases", UFR de Médecine Active, not recruiting
Nîmes Cedex 2, France, 30908
CHRU de Nîmes - Hôpital Universitaire Carémeau Active, not recruiting
Nîmes Cedex 9, France, 30029
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nīmes
Investigators
Study Director: Catherine Dunyach-Rempy, PharmD, PhD Centre Hospitalier Universitaire de Nîmes
Principal Investigator: Jean Philippe Lavigne, MD, PhD Centre Hospitalier Universitaire de Nîmes
  More Information

No publications provided

Responsible Party: Centre Hospitalier Universitaire de Nīmes
ClinicalTrials.gov Identifier: NCT01961310     History of Changes
Other Study ID Numbers: AOIt/2012/JPL-01, 2013-A00888-37
Study First Received: October 9, 2013
Last Updated: March 3, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
France: Committee for the Protection of Personnes

Keywords provided by Centre Hospitalier Universitaire de Nīmes:
bacterial translocation
intestinal microbiota

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases

ClinicalTrials.gov processed this record on October 21, 2014