Oral Metagenomic Biomarkers in Rheumatoid Arthritis

NCT02544334 | Completed

• 3 other identifiers: IRB2015002861171232512.420
• Study Type: observational
• Target: 92
• Locations: 1 country
• Sites: 2

Brief Summary

Rheumatoid Arthritis (RA) is a chronic and potentially severe autoimmune disease affecting 2 million in the United States. The role of environmental factors in modulating autoimmunity pathogenesis has been clearly described and yet the specific mechanisms of action remain poorly understood. A growing body of evidence implicates microbiota of mucosal surfaces in the development of autoimmune disorders. Various studies have clearly linked RA to periodontal disease. The latter is linked to the red-complex that includes the oral bacterium Porphyromonas gingivalis. And yet there has not been a systematic analysis of the oral microbiota in RA to determine whether there are specific markers for P. gingivalis (and other oral bacteria) that are linked to RA. In this study, the investigators will characterize oral microbial composition (microbiome) and gene content (metagenome) of DNA isolated from oral samples obtained from patients with (i) early stage RA prior to biologics treatments and (ii) subsets of RA patients who are responsive or unresponsive to anti-TNF-alpha therapy. The innovative aspect of this study is going beyond the identification of oral bacterial species, to the level of strains and genes that are associated with these groups. The overall hypothesis is that oral microbial variation exists between individuals that influences development of autoimmunity and autoimmune disease.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid arthritis; Metagenome; microbiome

Outcome Measures

Primary Outcomes (2)

• Oral microbiome will be catalogued in each group for their association with RA.

  A Wilcoxon rank-sum test will be computed on each profile to identify differential metagenomic gene content between each pair of groups (RA patients and controls). The potential microbial functional roles of the KEGG orthologues and eggnog orthologue groups markers in the oral microbiota of RA patients will also be assessed. All results will be corrected for multiple testing using a false discovery rate approach.

  Day 1

• Metagenomic analyses will be performed to find oral bacteria markers between the groups.

  A Wilcoxon rank-sum test will be computed on each profile to identify differential metagenomic gene content between each groups.

  18 months

Study Arms (4)

RA - naïve to biologics

This group will consist of 25 Rheumatoid Arthritis (RA) adult subjects who have not been treated with biologics (naïve to biologics). During the exam the following will take place: the multidimensional health assessment questionnaire (MDHAQ), dental exam, saliva collection, and dental plaque will be removed from different tooth surfaces for supragingival.

Procedure: Dental Plaque; Other: Multi-dimensional health assessment questionnaire (MDHAQ); Other: Saliva Collection

Healthy Controls

This group will consist of 25 adult subjects which will be healthy controls from members of the same household as the 25 naive to biologics, and be of the same age. During the exam the following will take place: dental exam, saliva collection, and dental plaque will be removed from different tooth surfaces for supragingival.

Procedure: Dental Plaque; Other: Saliva Collection

RA responsive to anti-TNF

This group will consist of 25 adult subjects with Rheumatoid Arthritis (RA) who have been responsive to first line anti-TNF-alpha therapy. During the exam the following will take place: the multidimensional health assessment questionnaire (MDHAQ), dental exam, saliva collection, and dental plaque will be removed from different tooth surfaces for supragingival.

Procedure: Dental Plaque; Other: Multi-dimensional health assessment questionnaire (MDHAQ); Other: Saliva Collection

RA non responsive to anti-TNF

This group will consist of 25 adult subjects with Rheumatoid Arthritis (RA) who are resistant to two or more anti-TNF-alpha therapies, and be of the same age as the RA responsive to anti-TNF group. During the exam the following will take place: the multidimensional health assessment questionnaire (MDHAQ), dental exam, saliva collection, and dental plaque will be removed from different tooth surfaces for supragingival.

Procedure: Dental Plaque; Other: Multi-dimensional health assessment questionnaire (MDHAQ); Other: Saliva Collection

Interventions

Dental Plaque PROCEDURE

All participants will have dental plaque removed from different tooth surfaces for supragingival.

Healthy Controls; RA - naïve to biologics; RA non responsive to anti-TNF; RA responsive to anti-TNF

Multi-dimensional health assessment questionnaire (MDHAQ) OTHER

The RA groups will receive the multi-dimensional health assessment questionnaire (MDHAQ) for physical function, pain, and global status.

Also known as: MDHAQ

RA - naïve to biologics; RA non responsive to anti-TNF; RA responsive to anti-TNF

Saliva Collection OTHER

All participants will have a saliva collection.

Healthy Controls; RA - naïve to biologics; RA non responsive to anti-TNF; RA responsive to anti-TNF

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Rheumatoid Arthritis (RA) adult patients who have not been treated with biologics (naïve to biologics), RA patients responsive to first line anti-TNF therapy, RA patients who are resistant to two or more TNF antagonists, and healthy controls from age-matched members of the same household.

You may qualify if:

• with at least 10 natural uncrowned teeth (excluding third molars) must be present.

You may not qualify if:

• have less than 10 teeth;
• have been treated with antibiotics within the past 3 months, including patients that require antibiotic prophylaxis prior to dental treatment;
• are immune compromised individuals (HIV, AIDS, immuno-suppressive drug therapy);
• participate in another clinical study involving the use of dental products one week prior to the start of the washout period or during the study period; and
• are unwilling or unable to provide informed consent and follow the collection instructions.

Sponsors & Collaborators

• University of Florida: lead
• United States Department of Defense: collaborator
• VA Medical Center-Gainesville: collaborator

Study Sites (2)

University of Florida College of Dentistry-Periodontics

Gainesville, Florida, 32610, United States

Location

Randall Malcom VA Medical Center

Gainesville, Florida, 32611, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Supragingival dental plaque will be pooled from different tooth surfaces using sterile periodontal curettes. DNA samples will be subjected to deep sequencing.

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Dental Plaque Index

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Dental Health Surveys; Health Surveys; Surveys and Questionnaires; Data Collection; Epidemiologic Methods; Investigative Techniques; Dentistry; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Public Health Dentistry

Study Officials

• Michael R Bubb, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

• Edward K Chan, Ph.D.

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2015
• First Posted: September 9, 2015
• Study Start: May 1, 2016
• Primary Completion: August 8, 2019
• Study Completion: August 8, 2019
• Last Updated: August 12, 2019

Record last verified: 2019-08

Locations

US (2)