The MEDIPSA Clinical Trial

Study Overview
=================
Brief Summary
-----------------
The main purpose of this study is to validate the positive effect of Omnibiotic Stress Repair on patients with active psoriatic Arthritis.

Detailed Description
-----------------
This is a single center, double blind (patients and investigators), Placebo controlled randomized trial. Consecutive patients with Psoriatic Arthritis (PsA) in moderate disease activity (Psoriatic Arthritis Disease Activity Score: PASDAS >3.2 - <5.4) on a stable treatment (no immunomodulatory treatment change in the last 3 months) with biological (bDMARDs) and/or synthetic disease modifying anti-rheumatic drugs (sDMARDs) and/or glucocorticoids will be included in the study. Clinical assessment will be scheduled at baseline, 12 weeks and 24 weeks.

Official Title
-----------------
The Effect of Probiotic Modulation of Enteral Dysbiosis on dIsease Activity in Patients With PSoriatic Arthritis

Conditions
-----------------
Psoriatic Arthritis

Intervention / Treatment
-----------------
* Dietary Supplement: Omnibiotic Stress Repair (OBSR)
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female patient ≥18 years and <90 years of age PsA according to CASPAR criteria MoDA defined by a PASDAS >3.2 - <5.4 Stable immunomodulatory therapy for the last 12 weeks before baseline (no change in bDMARD/sDMARD/glucocorticoid treatment) Written informed consent Exclusion Criteria: History of bariatric surgery Prior use of probiotics in the last 24 weeks Use of probiotics, other than the study product, during the study period. Antibiotic therapy within the last 4 weeks before inclusion Inflammatory bowel disease Recent (less than 12 weeks) acute myocardial infarction or decompensated heart failure Recent (less than 12 weeks) stroke Known malignancy Inability of the patient to follow the treatment protocol Pregnancy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Omnibiotic Stress Repair (OBSR)<br>After randomisation, patients will receive a box with one sachet containing 3g of OBSR for each day. | Dietary Supplement: Omnibiotic Stress Repair (OBSR)<br>* OBSR is given orally once daily (3g) for 3 months<br>|
| Placebo Comparator: Placebo<br>After randomisation, patients will receive an identical box with one sachet containing 3g of Placebo for each day. | Other: Placebo<br>* Placebo is given orally once daily (3g) for 3 months<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on disease activity according to PASDAS categories | To test differences in response according to the Psoriatic Disease Activity Score (PASDAS, range 0-10, higher values indicate higher disease activity) after 3 months of intake of OBSR compared to placebo in PsA patients. Difference in response is defined by the different amount of patients shifting from moderate disease activity (PASDAS > 3.2 - < 5.4) to low disease activity or remission (PASDAS ≤ 3.2) in the two groups. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on disease activity according to PASDAS score | To test differences in disease activity according to the Psoriatic Disease Activity Score (PASDAS, range 0-10, higher values indicate higher disease activity) before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Effect on disease activity according to PASDAS categories independent of concomitant medication | To test differences in response according to the Psoriatic Disease Activity Score (PASDAS, range 0-10, higher values indicate higher disease activity) after 3 months of intake of OBSR compared to placebo in PsA patients independent of the concomitant medication. For this analysis a logistic regression analysis will be performed using response as dependent and concomitant medication and OBSR/Placebo as indipendent variables. | 3 months | 
| Longterm effect on disease activity according to PASDAS categories | To test differences in response according to the Psoriatic Disease Activity Score (PASDAS, range 0-10, higher values indicate higher disease activity) before and after probiotic intake at 3 and 6 months. Difference in response is defined by the different amount of patients shifting from moderate disease activity (PASDAS > 3.2 - < 5.4) to low disease activity or remission (PASDAS ≤ 3.2) in the two groups. | 3 and 6 months | 
| Impact of disease according to the PSAID-12 | To assess differences in disease impact according to the Psoriatic Arthritis Impact of Disease Score - 12 (PSAID-12, range 0-10, higher values indicating worse status) before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Impact of disease according to the TJC | To assess differences in disease impact according to the Tender joint count (TJC, range 0-68, higher values indicating worse status) before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Impact of disease according to the SJC | To assess differences in disease impact according to the Tender joint count (SJC, range 0-66, higher values indicating worse status) before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Pain assessed by PtPain VAS | To assess differences in pain measured by the patient pain visual analogue scale (Pt-VAS, range 0-10, higher values indicating worse status) before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Enthesitis assessed by the LEI | To assess differences in enthesitis according to the leeds enthesitis index (LEI, range 0-6, higher values indicating worse status) before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Dactylitis assessed by the DS | To assess differences in dactylitis according to the dactylitis score (DS, range 0-20, higher values indicating worse status) before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Impact of disease according to the PGA | To assess differences in disease impact according to the Patient global assessment (PGA, range 0-10, higher values indicating worse status) before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Impact of disease according to the EGA | To assess differences in physician's disease assessment according to the Evaluator global assessment (EGA, range 0-10, higher values indicating worse status) before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Impact of disease according to the SF-36 | To assess differences in disease impact according to the Short form health survey 36 (SF-36, Norm-based scores were used in analyses, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning) before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Dietary assessment according to the Diet-Questionnaire | To assess differences in diet according to the Diet-Questionnaire (15 questions on the type of diet and amount of food intake. Results will be depicted in a descriptive manner) before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Skin involvement according to the PASI | To assess differences in skin involvement according to the Psoriasis Area and Severity Index (PASI, range 0-72, higher values indicating worse skin involvement) before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Impact of skin involvement according to the DLQI | To assess differences in quality of life due to skin involvement according to the Dermatology Life Quality Index (DLQI, range 0-30, higher values indicating worse quality of life) before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Impact of disease according to the HAQ | To assess differences in disease impact according to the Health Assessment Questionnaire (HAQ, range 0-3, higher values indicating worse status) before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Fatigue assessment accoring to the FACIT | To assess differences in fatigue according to the functional assessment of chronic illness therapy for fatigue (FACIT, range 0-52, higher values indicating worse fatigue) before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Hospital anxietey and depression assessment according to the HADS | To assess differences in hospital anxietey and depression according to the Hospital Anxiety and Depression Scale (HADS, range 0-21, higher values indicating worse status) before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Laboratory inflammation assessment according to ESR | To assess differences in disease impact according to the Erythrocyte sedimentation rate (ESR, mm, higher values indicating worse status) before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Laboratory inflammation assessment according to CRP | To assess differences in laboratory inflammation according to the C-reactive protein (CRP, mg/L. Higher values indicating worse status) before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Change in gut microbiota | To assess differences in gut microbiota composition (according to 16S rRNA targeted Amplicon Sequencing (%), displayed descriptively) before and after probiotic intake and between the OBSR and placebo control before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Gut permeability according to Zonulin | To assess differences in gut permeability according to stool Zonulin (ELISA, ng/ml, values above 55 indicate higher permeability) before and after probiotic intake and between the OBSR and placebo control before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Gut inflammation according to Calprotectin | To assess differences in gut inflammation according to stool Calprotectin (ELISA, mg/l, values above 50 indicate inflammation) before and after probiotic intake and between the OBSR and placebo control before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Neutrophile function according to Phagocytosis assessment | To assess differences in neutrophile function according to Phagocytosis assessment (Phagotest, normal values 95-99%, lower values indicate less function, Phagoburst, normal values 97-100% (E.coli stimulus), 1-10% (fMLP stimulus), 98-100% (PMA stimulus) before and after probiotic intake and between the OBSR and placebo control before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Inflammation assessment according to cytokine Level | To assess differences in cytokine levels in blood and synovial fluid (Interleukin (IL) pg/ml with normal ranges: IL-1 (<238), IL-5 (<19.27), IL-6 (<7.0), IL-8 (<10.59), IL-10 (<10.05), IL-17A (<11.14), IL-18 (37.43), IFN Alpha (<1.80), IFN Gamma (<6.82), TNF Alpha (<18.88)) before and after probiotic intake and between the OBSR and placebo control before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Lymphocyte subtypes according to FACS | To assess differences in lymphocyte subtypes according to fluorescence activated cell sorting (FACS, %) before and after probiotic intake and between the OBSR and placebo control before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 
| Metabolic assessment using NMR | To assess metabolomic differences in stool, serum and synovial fluid using nuclear magnetic resonance (NMR metabolic profiling, results are shown in a descriptive manner) before and after probiotic intake and between the OBSR and placebo control before and after probiotic intake at 3 and 6 months and between the OBSR and placebo control group at 3 months. | 3 and 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
psoriatic arthritis, probiotics, microbiome