The Role of Microbiome on Biological Therapy Efficacy in axSpA and RA

Arthritis, Rheumatoid Clinical Trial

— MicroSpA & RA  

Official title:

MicroSpA & MicroRA: The Role of Microbiome on Biological Therapy Efficacy in Axial Spondyloarthritis and Rheumatoid Arthritis - a New Paradigm

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04973787
• Other study ID #: MicroSpA
• Status: Recruiting
• Start date: August 1, 2020
• Est. completion date: January 31, 2022

Study information

• Verified date: July 2021
• Source: Universidade Nova de Lisboa
• Contact: Ana Faria, PhD
• Phone: 00351218803033
• Email: ana.faria[@]nms.unl.pt
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: January 31, 2022
• Est. primary completion date: January 31, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Axial Spondyloarthritis
• Spondylarthritis

Intervention

Biological:
• biological disease-modifying antirheumatic drugs (bDMARDs)
bDMARD therapy (TNF inhibitors), according to the Portuguese recommendations for the use of biological therapies in patients with axSpA and RA

Locations

Country	Name	City	State
Portugal	Centro Hospitalar Baixo Vouga - Hospital Infante D. Pedro	Aveiro
Portugal	Hospital de Braga, E.P.E.	Braga
Portugal	Hospital Sousa Martins - Unidade de Saúde Local da Guarda	Guarda
Portugal	Centro Hospitalar Lisboa Ocidental - Hospital Egas Moniz	Lisboa
Portugal	Centro Hospitalar Universitário de Lisboa Norte - Hospital Santa Maria	Lisboa
Portugal	Instituto Português de Reumatologia	Lisboa
Portugal	Centro Hospitalar Universitário São João	Oporto
Portugal	Unidade Local de Saúde do Alto Minho, Hospital Conde de Bertiandos	Ponte de Lima
Portugal	Centro Hospitalar de Médio Tejo - Hospital Rainha Santa Isabel - Torres Novas	Torres Novas
Portugal	Centro Hospitalar de Vila Nova da Gaia/Espinho	Vila Nova De Gaia

Sponsors (14)

Lead Sponsor

Collaborator

Universidade Nova de Lisboa

Centro Hospitalar Baixo Vouga - Hospital Infante D. Pedro, Centro Hospitalar de Vila Nova de Gaia/Espinho, Centro Hospitalar Lisboa Ocidental Hospital Egas Moniz, Centro Hospitalar Médio Tejo - Hospital Rainha Santa Isabel - Torres Novas, Centro Hospitalar Universitário de Lisboa Norte - Hospital de Santa Maria, Centro Hospitalar Universitário de São João, CHRC-Comprehensive Health Research Centre, FCM|NMS, UNL, Hospital de Braga E.P.E., Hospital Sousa Martins - Unidade de Saúde Local da Guarda, iNOVA4Health - Rheumatic Diseases Lab, Instituto Português de Reumatologia, NOVA Medical School of Universidade NOVA de Lisboa, Unidade Local de Saúde do Alto Minho, Hospital Conde de Bertiandos

Country where clinical trial is conducted

Portugal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Oral and gut microbiota characterization in axSpA and RA patients at baseline		Before bDMARD
Primary	Oral and gut microbiota characterization in axSpA and RA patients at week 14		14 weeks after start bDMARD
Primary	Disease activity measured by ASAS20 in axSpA and ACR20 in RA		14 weeks after start bDMARD
Secondary	Changes in Erythrocyte Sedimentation Rate (ESR, measured in mm/h)		Before bDMARD and 14-week after start bDMARD
Secondary	Changes in High-sensitivity C-reactive protein (hsCRP, measured in mg/dL)		Before bDMARD and 14-week after start bDMARD
Secondary	Disease activity characterization using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in axSpA	Scale from 0 (worse outcome) to 10 (better outcome)	Before bDMARD and 14-week after start bDMARD
Secondary	Disease activity characterization using Ankylosing Spondylitis Disease Activity Score - C-Reactive Protein (ASDAS-CRP) in axSpA	< 1.3 Inactive disease; > 3.5 Very high disease activity	Before bDMARD and 14-week after start bDMARD
Secondary	Disease activity characterization using Disease Activity Score-28 for Rheumatoid Arthritis with C-Reactive Protein (DAS28-CRP) for RA	Score greater than 5.1 implies active disease, less than 3.2 low disease activity, and less than 2.6 remission	Before bDMARD and 14-week after start bDMARD
Secondary	Quality of life evaluation with Short form 36 (SF36) at baseline and week 14	Score from 0 (worse outcome) to 100 (better outcome)	Before bDMARD and 14-week after start bDMARD
Secondary	Quality of life evaluation with Ankylosing Spondylitis Quality of Life (ASQOL) at baseline and week 14	Range from 0 -18 - High scores indicate worse quality of life	Before bDMARD and 14-week after start bDMARD
Secondary	Quality of life evaluation with Health Assessment Questionnaire (HAQ) at baseline and week 14	Scores of 0 to 1 are generally considered to represent mild to moderate difficulty, 1 to 2 moderate to severe disability, and 2 to 3 severe to very severe disability	Before bDMARD and 14-week after start bDMARD
Secondary	Quality of life evaluation regarding depression and anxiety using Hospital Anxiety and Depression Scale (HADS) at baseline and week 14	Scores of less than 7 indicate non-cases; 8-10 Mild; 11-14 Moderate;15-21 Severe	Before bDMARD and 14-week after start bDMARD
Secondary	Fatigue evaluation at baseline and week 14	Visual analogic scale (0-10)	Before bDMARD and 14-week after start bDMARD