Oral Metagenomic Biomarkers in Rheumatoid Arthritis
| Status: | Recruiting |
|---|---|
| Conditions: | Arthritis, Rheumatoid Arthritis |
| Therapuetic Areas: | Rheumatology |
| Healthy: | No |
| Age Range: | 18 - 85 |
| Updated: | 9/16/2018 |
| Start Date: | May 2016 |
| End Date: | September 2019 |
| Contact: | Edward K Chan, Ph.D. |
| Email: | echan@ufl.edu |
| Phone: | 352-273-8849 |
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.
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.
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.
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.
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.
We found this trial at
2
sites
Gainesville, Florida 32610
Phone: 352-273-8849
Click here to add this to my saved trials
Click here to add this to my saved trials