Oral Metagenomic Biomarkers in Rheumatoid Arthritis

NCT ID: NCT02544334

Last Updated: 2019-08-12

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 92 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-05-31
• Study Completion Date: 2019-08-08

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.

Detailed Description

This is a multi-disciplinary research study with five investigators from different, yet complementary, disciplines to establish this new collaboration. There is a high translational potential for information gained from this project based on the collaboration of a rheumatologist, a dentist, oral biologists, and infectious disease experts with expertise in immunology, microbiology, and genomics. In brief, RA participants will be recruited by the rheumatologist. A total of 100 participants will be recruited for two groups to be studied; one group of subjects with RA and the other group will be healthy controls. These two groups will be divided into the following groups for participation in the study: Group 1: will consist of 25 RA adult subjects who have not been treated with biologics which will be compared to 25 healthy controls from age-matched members of the same household. Group 2 will consist of 25 RA adult subjects responsive to first line anti-TNF therapy which will be compared to 25 subjects of the same age and sex with RA who are resistant to two or more TNF antagonists. The participants will be scheduled for a research study visit at the University of Florida Dental Clinic Research Unit. 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.

The supragingival will be subjected to deep sequencing in the genomics lab. To test two specific aims: 1) testing the hypothesis that oral microbiome profiles based on 16S RNA data are associated with the development of RA or with the response to a specific therapy, and 2) testing the hypothesis that the specific genes, variants, and functional capabilities (metagenome) are associated with RA or with therapeutic response. Upon completion of this pilot study, the investigators will have systematically identified bacterial biomarkers (e.g. species, subspecies, genes) that correlate with RA and may serve as potential targets for disease treatment. These markers may be developed into new drug targets for RA therapy in future studies.

Conditions

Rheumatoid Arthritis

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

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.

Dental Plaque

Intervention Type: PROCEDURE

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

Multi-dimensional health assessment questionnaire (MDHAQ)

Intervention Type: OTHER

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

Saliva Collection

Intervention Type: OTHER

All participants will have a 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.

Dental Plaque

Intervention Type: PROCEDURE

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

Saliva Collection

Intervention Type: OTHER

All participants will have a 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.

Dental Plaque

Intervention Type: PROCEDURE

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

Multi-dimensional health assessment questionnaire (MDHAQ)

Intervention Type: OTHER

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

Saliva Collection

Intervention Type: OTHER

All participants will have a 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.

Dental Plaque

Intervention Type: PROCEDURE

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

Multi-dimensional health assessment questionnaire (MDHAQ)

Intervention Type: OTHER

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

Saliva Collection

Intervention Type: OTHER

All participants will have a saliva collection.

Interventions

Dental Plaque

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

Intervention Type: PROCEDURE

Multi-dimensional health assessment questionnaire (MDHAQ)

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

Intervention Type: OTHER

Saliva Collection

All participants will have a saliva collection.

Intervention Type: OTHER

Other Intervention Names

MDHAQ

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

United States Department of Defense

FED

Sponsor Role: collaborator

VA Medical Center-Gainesville

FED

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael R Bubb, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Edward K Chan, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

University of Florida College of Dentistry-Periodontics

Gainesville, Florida, United States

Randall Malcom VA Medical Center

Gainesville, Florida, United States

Countries

United States

Other Identifiers

11712325

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

12.420

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

IRB201500286

Identifier Type: -

Identifier Source: org_study_id