Rheumatoid ArthritisNCT02544334
Oral Metagenomic Biomarkers in Rheumatoid Arthritis
An observational study of Rheumatoid Arthritis, run by University of Florida at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Dental Plaque, Multi-dimensional health assessment questionnaire (MDHAQ) and Saliva Collection
- Type of treatment
- Surgery or procedure
- How many people
- 92 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2016to 8 Aug 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- with at least 10 natural uncrowned teeth (excluding third molars) must be present.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Florida College of Dentistry-Periodontics
Gainesville, Florida, 32610
Randall Malcom VA Medical Center
Gainesville, Florida, 32611
About this study
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.
Read the 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
- Being tested
- Dental Plaque, Multi-dimensional health assessment questionnaire (MDHAQ), Saliva Collection
- Keywords
- Rheumatoid arthritis, Metagenome, microbiome
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dental PlaqueProcedure or surgery
All participants will have dental plaque removed from different tooth surfaces for supragingival.
Multi-dimensional health assessment questionnaire (MDHAQ)Other
Also called MDHAQ
The RA groups will receive the multi-dimensional health assessment questionnaire (MDHAQ) for physical function, pain, and global status.
Saliva CollectionOther
All participants will have a saliva collection.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Procedure: Dental Plaque; Other: Multi-dimensional health assessment questionnaire (MDHAQ); Other: Saliva Collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2015 (estimated)
- Study startMay 2016
- Primary completion8 Aug 2019
- Study completion8 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense, VA Medical Center-Gainesville
- Responsible party
- Sponsor
- Investigators
- Michael R Bubb, MD, Principal investigator, University of FloridaEdward K Chan, Ph.D., Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02544334
- Sponsor's protocol ID
- IRB201500286
- Other IDs
- 11712325, 12.420
- Status last verified
- Aug 2019
- First submitted
- 31 Aug 2015
- Last updated
- 12 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oral Metagenomic Biomarkers in Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT02544334
- Acronym / sponsor ID
- IRB201500286
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid arthritis, Metagenome, microbiome
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- United States Department of Defense, VA Medical Center-Gainesville
- Study start
- May 2016
- Primary completion
- 8 Aug 2019 (actual)
- Study completion
- 8 Aug 2019 (actual)
- First posted
- 9 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| RA - naïve to biologics | – | Procedure: Dental Plaque, Other: Multi-dimensional health assessment questionnaire (MDHAQ), Other: Saliva CollectionThis 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. |
| Healthy Controls | – | Procedure: Dental Plaque, Other: Saliva CollectionThis 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. |
| RA responsive to anti-TNF | – | Procedure: Dental Plaque, Other: Multi-dimensional health assessment questionnaire (MDHAQ), Other: Saliva CollectionThis 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. |
| RA non responsive to anti-TNF | – | Procedure: Dental Plaque, Other: Multi-dimensional health assessment questionnaire (MDHAQ), Other: Saliva CollectionThis 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (1 listed)
- with at least 10 natural uncrowned teeth (excluding third molars) must be present.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dental PlaqueAll participants will have dental plaque removed from different tooth surfaces for supragingival. | Procedure or surgery | Healthy Controls, RA - naïve to biologics, RA non responsive to anti-TNF, RA responsive to anti-TNF |
| Multi-dimensional health assessment questionnaire (MDHAQ)Also: MDHAQThe RA groups will receive the multi-dimensional health assessment questionnaire (MDHAQ) for physical function, pain, and global status. | Other | RA - naïve to biologics, RA non responsive to anti-TNF, RA responsive to anti-TNF |
| Saliva CollectionAll participants will have a saliva collection. | Other | Healthy Controls, RA - naïve to biologics, RA non responsive to anti-TNF, RA responsive to anti-TNF |
Primary outcome
Oral microbiome will be catalogued in each group for their association with RA.
Time frame: Day 1
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.
Metagenomic analyses will be performed to find oral bacteria markers between the groups.
Time frame: 18 months
A Wilcoxon rank-sum test will be computed on each profile to identify differential metagenomic gene content between each groups.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2019.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael R Bubb, MD principal investigator
University of Florida
Edward K Chan, Ph.D. principal investigator
University of Florida
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rheumatoid Arthritis, run by University of Florida at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Oral microbiome will be catalogued in each group for their association with RA. (time frame: Day 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2019.