Rheumatoid ArthritisNCT05777577
Immunological Profile and Microbial Markers in Evaluating the Effectiveness of Probiotic Therapy in RA Patients
A study testing probiotic therapy in people with Rheumatoid Arthritis, run by Nazarbayev University.
Trial summary
Rheumatoid arthritis (RA) is a common, chronic autoimmune disease that causes joint damage and deformity associated with an increased disability risk and shortened life expectancy (1). Read more about this study
- Who is it for?
- Ages 30 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- probiotic therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- Mar 2023to Dec 2024
- Phase
- Interventional
- 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 30 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- ● age 30-50 years old
- signed informed consent
- Have a clinical diagnosis of RA (according to American College of Rheumatologyhttps (ACR) criteria)
- Have been on stable RA treatment and are expected to remain on stable RA treatment during the study (ie, current medications and/or other therapies such as physical therapy are allowed, excluding immunotherapy).
- Have at least 4 swollen and painful joints on a 64/66 scale.
- absence of acute infectious diseases at the time of recruitment
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- absence of exacerbations of chronic diseases at the time of recruitment
- no history of regular use of probiotic-containing products
- no history of the use of any drugs that affect the composition of the microbiome during the last three months: antibiotics, probiotic, prebiotics, metabiotics, postbiotic
Who cannot join
- ● History of any systemic disease such as diabetes, autoimmune disease, cancer (excluding basal and squamous cell skin cancer, which have been cured) !!! taking into account the main study group
- History of gastrointestinal or liver disease known to be associated with changes in intestinal flora
- Use of any of the drugs listed below within the past 6 months:
- systemic antibiotics, antifungal, antiviral or antiparasitic (intravenously, intramuscularly or orally);
- oral, intravenous, intramuscular, nasal or inhaled corticosteroids;
- cytokines;
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- large doses of commercial probiotic (greater than or equal to 10^8 cfu per day) - includes tablets, capsules, dragees, chewing gums or powders, where probiotic bacteria is the main component
- Use of topical antibiotics or topical steroids on the face, scalp or neck, or on the arms, forearms, hands within the previous 7 days.
- Acute illness at the time of inclusion in the sample. Acute illness is defined as the presence of moderate or severe illness with or without fever.
- Chronic diseases requiring current medical treatment
- Unstable dietary history, major changes in diet during the previous month.
- Positive test for HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV).
- Gastrointestinal surgery, excluding cholecystectomy and appendectomy in the last five years. Any major bowel resection at any time.
- Regular urinary incontinence
- Feeding or pregnancy.
- Have had warts or human papillomavirus (HPV) with a confirmed diagnosis within the previous 2 years.
- Treatment or suspected toxic shock syndrome.
- Rheumatoid arthritis:
- Probable rheumatoid arthritis
- Late stage disease
- Special clinical forms of the disease: Felty's syndrome, Still's disease in adults
- Overlap syndrome, paraneoplastic syndrome
Trial locations and contacts
No sites are listed yet.
About this study
Rheumatoid arthritis (RA) is a common, chronic autoimmune disease that causes joint damage and deformity associated with an increased disability risk and shortened life expectancy (1). New treatment methods have significantly improved disease control, but remission is still difficult to be achieved, so new and improved treatment and diagnostic options are needed for patients stratification and prognosis. To achieve this goal, the proposed study will be aimed at studying RA main factors' relationship. The project's central theme is that microbial dysbiosis is a critical determinant of RA pathogenesis, and the interaction between human factors and the microbiome contributes to the disease risk and it's activity.
Read the detailed description
The microbiome plays a fundamental role in diseases and human health. Technological advances in recent decades have expanded our understanding of microbes and their ability to form innate and acquired human immune responses. Advances in understanding the microbiome's impact on human immunity, along with the realization that inflammatory processes underlie a number of common diseases, including RA, necessitates an interdisciplinary approach to studying the interaction of humans and microbes at various levels. Modern sequencing technologies and new tools development for analyzing metagenomic data allow us to understand better the complex relationship between the dynamic microbes community inhabiting mucous tissues and the human immune system. Such analysis is especially relevant in Central Asia, since the investigators not only identified ethnic differences in risk loci, but also found that the composition of the intestinal and oral microbiota of Kazakhs is unique and significantly differs from the corresponding microbiota in other world regions, due to lifestyle factors characteristic of Kazakhstan and common to the whole Central Asia.
The main research's purpose is to study the complex relationship between microbiome dysbiosis, local and systemic inflammation in relation to RA pathogenesis and the disease activity in the Kazakhstan population. The investigators assume that patients with RA have greater dysbiosis (local microbiota violation) in the intestine and oral cavity compared to the control group, and that it is due to a greater inflammatory response and disease activity.
To consider this hypothesis, microbiome biomarkers of the oral cavity and gut in RA will be identified, RA patients immunological parameters in blood, stool and saliva samples will be analyzed, an dynamics assessment of the microbiome and immunological profile against the probiotic therapy background and an analysis of the relationships between microbiome and immunological profiles will be carried out.
The research's scientific novelty and significance consist in the study of the local and general immune status in combination with the microbiomes of the oral cavity and gut in RA. The results are likely not only to give a new insight into the relationship between human factors and pathogenic factors, but may also affect the RA diagnosis, the disease activity prognosis and inform preventive strategies. Thus, a better understanding of the complex microbial interactions with the immune system of the mucous membrane in RA can advance our understanding of RA pathophysiology, help predict future relapses, develop strategies for prevention and early diagnosis, and lead to new therapeutic directions' development aimed at the microbiome.
The results impact on the science and technology development contribute to the first comprehensive study of the RA pathogenesis in the Central Asian population. The investigators expect not only to receive important new information about the RA etiopathogenesis, but also the complex interaction that determines the pathogenesis and disease activity. The proposed study has the potential not only to improve the methods of diagnosis and monitoring of RA patients in Kazakhstan, but also can contribute to a better RA understanding in general, paving the way for personalized diagnosis and treatment of rheumatic diseases.
- Conditions
- Rheumatoid Arthritis
- Being tested
- probiotic therapy
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
probiotic therapyDietary supplement
probiotic including bifidobacterium
| Study group | Role | What they receive |
|---|---|---|
| Rheumatoid Arthritis Probiotic (RAP) | Experimental | patients with RA 30-50 yers old, who have 4 or more swollen and painful joints, who did not take probiotic and other drugs that affect the microbiome Receives: Dietary Supplement: probiotic therapy |
| Rheumatoid Arthritis Probiotic1 (RAP1) | Active comparator | closest relatives (brothers and sister, children, parents) living in the same living area and corresponding to the age group, without RA, who did not take probiotic and other drugs that affect the microbiome Receives: Dietary Supplement: probiotic therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
the oral cavity and gut microbiome
An analysis of the biodiversity of the oral cavity and intestine will be carried out against the background of probiotic therapy: Alpha and Betta diversity according to the main indices: Chao1, Shannon, Simpson etc. The number of taxa associated with the severity of RA will be estimated using LDA. It will be analyzed to what extent probiotic therapy corrects the functional profile of the oral and intestinal microbiomes.
Measured: Change from Baseline the oral cavity and gut microbiome immediately after probiotic therapy
the oral cavity and gut microbiome
An analysis of the biodiversity of the oral cavity and intestine will be carried out against the background of probiotic therapy: Alpha and Betta diversity according to the main indices: Chao1, Shannon, Simpson etc. The number of taxa associated with the severity of RA will be estimated using LDA. It will be analyzed to what extent probiotic therapy corrects the functional profile of the oral and intestinal microbiomes.
Measured: Change from Baseline the oral cavity and gut microbiome at 1 month
Secondary outcomes (2)
the immunological profile
the levels of the following inflammatory cytokines, chemokines and immunoglobulins will be measured in stool samples, oral swabs and blood: sCD40L (pg/mL) , EGF (pg/mL), Eotaxin/CCL11(pg/mL), FGF-2 (pg/mL), Flt-3 ligand (pg/mL), Fractalkine (pg/mL), G-CSF (pg/mL), GM-CSF (pg/mL), GRO (pg/mL), IFN-α2 (pg/mL), IFN-γ (pg/mL), IL-1α (pg/mL), IL-1β (pg/mL), IL-1ra (pg/mL), IL-2 (pg/mL), IL-3 (pg/mL), IL-4 (pg/mL), IL-5 (pg/mL), IL-6 (pg/mL), IL-7(pg/mL), IL-8(pg/mL), IL-9(pg/mL), IL-10(pg/mL), IL-12 (p40)(pg/mL), IL-12 (p70)(pg/mL), IL-13(pg/mL), IL-15(pg/mL), IL-17A(pg/mL), IP-10(pg/mL), MCP-1(pg/mL), MCP-3(pg/mL), MDC (CCL22)(pg/mL), MIP-1α(pg/mL), MIP-1β(pg/mL), PDGF-AA(pg/mL), PDGF-AB/BB(pg/mL), RANTES(pg/mL), TGF-α(pg/mL), TNF-α(pg/mL), TNF-β(pg/mL), VEGF(pg/mL), IgA (g/L), IgG1-G4 (g/L), IgM (g/L).
Measured: Change from Baseline the oral cavity and gut microbiome immediately after probiotic therapy
the immunological profile
the levels of the following inflammatory cytokines, chemokines and immunoglobulins will be measured in stool samples, oral swabs and blood: sCD40L (pg/mL) , EGF (pg/mL), Eotaxin/CCL11(pg/mL), FGF-2 (pg/mL), Flt-3 ligand (pg/mL), Fractalkine (pg/mL), G-CSF (pg/mL), GM-CSF (pg/mL), GRO (pg/mL), IFN-α2 (pg/mL), IFN-γ (pg/mL), IL-1α (pg/mL), IL-1β (pg/mL), IL-1ra (pg/mL), IL-2 (pg/mL), IL-3 (pg/mL), IL-4 (pg/mL), IL-5 (pg/mL), IL-6 (pg/mL), IL-7(pg/mL), IL-8(pg/mL), IL-9(pg/mL), IL-10(pg/mL), IL-12 (p40)(pg/mL), IL-12 (p70)(pg/mL), IL-13(pg/mL), IL-15(pg/mL), IL-17A(pg/mL), IP-10(pg/mL), MCP-1(pg/mL), MCP-3(pg/mL), MDC (CCL22)(pg/mL), MIP-1α(pg/mL), MIP-1β(pg/mL), PDGF-AA(pg/mL), PDGF-AB/BB(pg/mL), RANTES(pg/mL), TGF-α(pg/mL), TNF-α(pg/mL), TNF-β(pg/mL), VEGF(pg/mL), IgA (g/L), IgG1-G4 (g/L), IgM (g/L).
Measured: Change from Baseline the oral cavity and gut microbiome at 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2023
- Study startMar 2023 (estimated)
- Primary completionDec 2023 (estimated)
- Study completionDec 2024 (estimated)
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.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nazarbayev University
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Education and Science, Republic of Kazakhstan
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05777577
- Sponsor's protocol ID
- AP14869993
- Status last verified
- Feb 2023
- First submitted
- 31 Jan 2023
- Last updated
- 21 Mar 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunological Profile and Microbial Markers in Evaluating the Effectiveness of Probiotic Therapy in RA Patients
- ClinicalTrials.gov ID
- NCT05777577
- Acronym / sponsor ID
- AP14869993
- Conditions
- Rheumatoid Arthritis
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Nazarbayev UniversityUniversity, hospital or other
- Collaborators
- Ministry of Education and Science, Republic of Kazakhstan
- Study start
- Mar 2023 (estimated)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 21 Mar 2023 (actual)
- 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 common, chronic autoimmune disease that causes joint damage and deformity associated with an increased disability risk and shortened life expectancy (1). New treatment methods have significantly improved disease control, but remission is still difficult to be achieved, so new and improved treatment and diagnostic options are needed for patients stratification and prognosis. To achieve this goal, the proposed study will be aimed at studying RA main factors' relationship. The project's central theme is that microbial dysbiosis is a critical determinant of RA pathogenesis, and the interaction between human factors and the microbiome contributes to the disease risk and it's activity.
Detailed description
The microbiome plays a fundamental role in diseases and human health. Technological advances in recent decades have expanded our understanding of microbes and their ability to form innate and acquired human immune responses. Advances in understanding the microbiome's impact on human immunity, along with the realization that inflammatory processes underlie a number of common diseases, including RA, necessitates an interdisciplinary approach to studying the interaction of humans and microbes at various levels. Modern sequencing technologies and new tools development for analyzing metagenomic data allow us to understand better the complex relationship between the dynamic microbes community inhabiting mucous tissues and the human immune system. Such analysis is especially relevant in Central Asia, since the investigators not only identified ethnic differences in risk loci, but also found that the composition of the intestinal and oral microbiota of Kazakhs is unique and significantly differs from the corresponding microbiota in other world regions, due to lifestyle factors characteristic of Kazakhstan and common to the whole Central Asia.
The main research's purpose is to study the complex relationship between microbiome dysbiosis, local and systemic inflammation in relation to RA pathogenesis and the disease activity in the Kazakhstan population. The investigators assume that patients with RA have greater dysbiosis (local microbiota violation) in the intestine and oral cavity compared to the control group, and that it is due to a greater inflammatory response and disease activity.
To consider this hypothesis, microbiome biomarkers of the oral cavity and gut in RA will be identified, RA patients immunological parameters in blood, stool and saliva samples will be analyzed, an dynamics assessment of the microbiome and immunological profile against the probiotic therapy background and an analysis of the relationships between microbiome and immunological profiles will be carried out.
The research's scientific novelty and significance consist in the study of the local and general immune status in combination with the microbiomes of the oral cavity and gut in RA. The results are likely not only to give a new insight into the relationship between human factors and pathogenic factors, but may also affect the RA diagnosis, the disease activity prognosis and inform preventive strategies. Thus, a better understanding of the complex microbial interactions with the immune system of the mucous membrane in RA can advance our understanding of RA pathophysiology, help predict future relapses, develop strategies for prevention and early diagnosis, and lead to new therapeutic directions' development aimed at the microbiome.
The results impact on the science and technology development contribute to the first comprehensive study of the RA pathogenesis in the Central Asian population. The investigators expect not only to receive important new information about the RA etiopathogenesis, but also the complex interaction that determines the pathogenesis and disease activity. The proposed study has the potential not only to improve the methods of diagnosis and monitoring of RA patients in Kazakhstan, but also can contribute to a better RA understanding in general, paving the way for personalized diagnosis and treatment of rheumatic diseases.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rheumatoid Arthritis Probiotic (RAP) | Experimental | Dietary Supplement: probiotic therapypatients with RA 30-50 yers old, who have 4 or more swollen and painful joints, who did not take probiotic and other drugs that affect the microbiome |
| Rheumatoid Arthritis Probiotic1 (RAP1) | Active comparator | Dietary Supplement: probiotic therapyclosest relatives (brothers and sister, children, parents) living in the same living area and corresponding to the age group, without RA, who did not take probiotic and other drugs that affect the microbiome |
Who may qualify
- Ages
- 30 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- ● age 30-50 years old
Key exclusion criteria (22 listed)
- ● History of any systemic disease such as diabetes, autoimmune disease, cancer (excluding basal and squamous cell skin cancer, which have been cured) !!! taking into account the main study group
- systemic antibiotics, antifungal, antiviral or antiparasitic (intravenously, intramuscularly or orally);
- oral, intravenous, intramuscular, nasal or inhaled corticosteroids;
- cytokines;
- large doses of commercial probiotic (greater than or equal to 10^8 cfu per day) - includes tablets, capsules, dragees, chewing gums or powders, where probiotic bacteria is the main component
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 |
|---|---|---|
| probiotic therapyprobiotic including bifidobacterium | Dietary supplement | Rheumatoid Arthritis Probiotic (RAP), Rheumatoid Arthritis Probiotic1 (RAP1) |
Primary outcome
the oral cavity and gut microbiome
Time frame: Change from Baseline the oral cavity and gut microbiome immediately after probiotic therapy
An analysis of the biodiversity of the oral cavity and intestine will be carried out against the background of probiotic therapy: Alpha and Betta diversity according to the main indices: Chao1, Shannon, Simpson etc. The number of taxa associated with the severity of RA will be estimated using LDA. It will be analyzed to what extent probiotic therapy corrects the functional profile of the oral and intestinal microbiomes.
the oral cavity and gut microbiome
Time frame: Change from Baseline the oral cavity and gut microbiome at 1 month
An analysis of the biodiversity of the oral cavity and intestine will be carried out against the background of probiotic therapy: Alpha and Betta diversity according to the main indices: Chao1, Shannon, Simpson etc. The number of taxa associated with the severity of RA will be estimated using LDA. It will be analyzed to what extent probiotic therapy corrects the functional profile of the oral and intestinal microbiomes.
2 secondary outcomes
the immunological profile
Time frame: Change from Baseline the oral cavity and gut microbiome immediately after probiotic therapy
the immunological profile
Time frame: Change from Baseline the oral cavity and gut microbiome at 1 month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2023.
- Individual participant dataSharing planned: No
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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.
Questions about this trial
What is this clinical trial studying?
A study testing probiotic therapy in people with Rheumatoid Arthritis, run by Nazarbayev University.
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 9 inclusion and 22 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: status not confirmed, as of the sponsor's last update on 21 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Almagul Kushugulova, Professor (+7172 706498, akushugulova@nu.edu.kz), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the oral cavity and gut microbiome (time frame: Change from Baseline the oral cavity and gut microbiome immediately after probiotic therapy). 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 21 Mar 2023.