Clinical trial NCT04973787: The Role of Microbiome on Biological Therapy Efficacy in axSpA and RA
Official title: MicroSpA & MicroRA: The Role of Microbiome on Biological Therapy Efficacy in Axial Spondyloarthritis and Rheumatoid Arthritis - a New Paradigm
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Axial Spondyloarthritis
Arthritis, Rheumatoid
Keywords: Tumor Necrosis Factor alpha inhibitor
Microbiota
Biomarker
Lead sponsor: Universidade Nova de Lisboa
Sponsor class: OTHER
Collaborators: name: Centro Hospitalar Lisboa Ocidental Hospital Egas Moniz
name: Centro Hospitalar De São João, E.P.E.
name: Centro Hospitalar de Vila Nova de Gaia/Espinho
name: Centro Hospitalar Universitário de Lisboa Norte - Hospital de Santa Maria
name: Instituto Português de Reumatologia
name: Centro Hospitalar Médio Tejo - Hospital Rainha Santa Isabel - Torres Novas
name: Centro Hospitalar Baixo Vouga - Hospital Infante D. Pedro
name: Comprehensive Health Research Center
name: iNOVA4Health - Rheumatic Diseases Lab
name: Unidade Local de Saúde do Alto Minho, Hospital Conde de Bertiandos
name: Hospital de Braga E.P.E.
name: Hospital Sousa Martins - Unidade de Saúde Local da Guarda
First posted: 2021-07-22
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with axSpA or RA according to ASAS and 2010 ACR/EULAR classification criteria, respectively, with indication to start bDMARD according to Portuguese Rheumatology Society.

Brief summary: Spondyloarthritis (SpA) and Rheumatoid arthritis (RA) are among the most common chronic inflammatory rheumatic diseases. Introduction of Tumor Necrosis Factor alpha inhibitors (TNFi) to the therapeutic strategy improved acute inflammation and pain, but a significant percentage of patients develop severe adverse events or are still non responders or incomplete responders to these expensive treatments. There is an urgent need to identify new predictors of biological therapy response. It has been described the role of microbiota in some rheumatic diseases, however, clinical trials are scarce. We hypothesized that microbiota or their metabolites may play a role in therapeutic response to TNFi.

Detailed description: Thus, this project aimed to evaluate the influence of oral and gut microbiota in the therapeutic response to biologic therapies, in 60 patients.

It is expected to enrolled 30 SpA and 30 RA patients and 30 controls, crossed by gender, age and diet profile. Oral and fecal microbiota will be characterized before TNFi therapeutic. Patients will have an additional microbiota and metabolic profile characterization 14 weeks late after.

This will allow to identify specific profiles of oral and gut microbiome and/or specific biochemical patterns in these patients. At week 14 it will be possible to identify changes induced by TNFi. In addition, it will be possible to identify microbiota pattern associated clinical therapeutic TNFi response vs non-response.

This will allow to predict isolate microbe or microbes patterns at baseline associated to clinical response obtained at week 14. These results may additionally contribute to clinical decision and a better evidenced-based treatment.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of axSpA (according to ASAS classification criteria) or RA (according to 2010 ACR/EULAR classification criteria);
2. Indication for bDMARD therapy, according to the Portuguese recommendations for the use of biological therapies in patients with axSpA and RA;
3. Oral corticosteroids (equivalent to prednisolone ≤ 10mg/day) and/or nonsteroidal anti-inflammatory drugs allowed at stable dose ≥4 weeks before baseline;
4. Conventional DMARDs allowed at stable dose ≥12 weeks before baseline;
5. Ability to provide informed consent.

Exclusion Criteria:

1. History of rheumatic disorder other than axSpA or RA;
2. History of Inflammatory Bowel Disease;
3. Previous treatment with bDMARD;
4. Current pregnancy or breastfeeding;
5. Malignancy (except for completely treated squamous or basal cell carcinoma);
6. Any uncontrolled medical condition (e.g., uncontrolled diabetes mellitus, unstable ischemic heart disease);
7. History of any documented gastrointestinal disease or tract surgery leaving permanent residua (e.g., gastrectomy, bariatric surgery, or colectomy);
8. Intraarticular injections of extra-axial joints and tendons within 28 days before or at baseline;
9. Recent (\<3 months prior) use of any antibiotic therapy, current extreme diet (e.g., parenteral nutrition or macrobiotic diet), current consumption of probiotics.

Control group will be healthy participants, and the same inclusion and exclusion criteria will be applied except for rheumatic disease diagnosis.

Primary outcomes:
measure: Oral and gut microbiota characterization in axSpA and RA patients at baseline
timeFrame: Before bDMARD
measure: Oral and gut microbiota characterization in axSpA and RA patients at week 14
timeFrame: 14 weeks after start bDMARD
measure: Disease activity measured by ASAS20 in axSpA and ACR20 in RA
timeFrame: 14 weeks after start bDMARD
Secondary outcomes:
measure: Changes in Erythrocyte Sedimentation Rate (ESR, measured in mm/h)
timeFrame: Before bDMARD and 14-week after start bDMARD
measure: Changes in High-sensitivity C-reactive protein (hsCRP, measured in mg/dL)
timeFrame: Before bDMARD and 14-week after start bDMARD
measure: Disease activity characterization using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in axSpA
timeFrame: Before bDMARD and 14-week after start bDMARD
measure: Disease activity characterization using Ankylosing Spondylitis Disease Activity Score - C-Reactive Protein (ASDAS-CRP) in axSpA
timeFrame: Before bDMARD and 14-week after start bDMARD
measure: Disease activity characterization using Disease Activity Score-28 for Rheumatoid Arthritis with C-Reactive Protein (DAS28-CRP) for RA
timeFrame: Before bDMARD and 14-week after start bDMARD
measure: Quality of life evaluation with Short form 36 (SF36) at baseline and week 14
timeFrame: Before bDMARD and 14-week after start bDMARD
measure: Quality of life evaluation with Ankylosing Spondylitis Quality of Life (ASQOL) at baseline and week 14
timeFrame: Before bDMARD and 14-week after start bDMARD
measure: Quality of life evaluation with Health Assessment Questionnaire (HAQ) at baseline and week 14
timeFrame: Before bDMARD and 14-week after start bDMARD
measure: Quality of life evaluation regarding depression and anxiety using Hospital Anxiety and Depression Scale (HADS) at baseline and week 14
timeFrame: Before bDMARD and 14-week after start bDMARD
measure: Fatigue evaluation at baseline and week 14
timeFrame: Before bDMARD and 14-week after start bDMARD
Other outcomes:
Locations:
city: Aveiro
country: Portugal
facility: Centro Hospitalar Baixo Vouga - Hospital Infante D. Pedro
city: Braga
country: Portugal
facility: Hospital de Braga, E.P.E.
city: Guarda
country: Portugal
facility: Hospital Sousa Martins - Unidade de Saúde Local da Guarda
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa Ocidental - Hospital Egas Moniz
city: Lisboa
country: Portugal
facility: Centro Hospitalar Universitário de Lisboa Norte - Hospital Santa Maria
city: Lisboa
country: Portugal
facility: Instituto Português de Reumatologia
city: Oporto
country: Portugal
facility: Centro Hospitalar Universitário São João
city: Ponte de Lima
country: Portugal
facility: Unidade Local de Saúde do Alto Minho, Hospital Conde de Bertiandos
city: Torres Novas
country: Portugal
facility: Centro Hospitalar de Médio Tejo - Hospital Rainha Santa Isabel - Torres Novas
city: Vila Nova De Gaia
country: Portugal
facility: Centro Hospitalar de Vila Nova da Gaia/Espinho
Study officials:
affiliation: Universidade Nova de Lisboa
name: Ana Faria, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: NOVA Medical School, Universidade NOVA de Lisboa; CHLO Hospital Egas Moniz
name: Fernando Pimentel-Santos, PhD Agg
role: PRINCIPAL_INVESTIGATOR
References: