The MEDIPSA Clinical Trial (MEDIPSA)

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

The main purpose of this study is to validate the positive effect of "Omnibiotic Stress Repair" on patients with active psoriatic Arthritis.

Study Overview

• Status: Completed
• Conditions: Psoriatic Arthritis
• Intervention / Treatment: Dietary supplement: Omnibiotic Stress Repair (OBSR); Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Styria
    • Graz, Styria, Austria, 8010
      • Medical University of Graz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female patient ≥18 years and <90 years of age
2. PsA according to CASPAR criteria
3. MoDA defined by a PASDAS >3.2 - <5.4
4. Stable immunomodulatory therapy for the last 12 weeks before baseline (no change in bDMARD/sDMARD/glucocorticoid treatment)
5. Written informed consent

Exclusion Criteria:

1. History of bariatric surgery
2. Prior use of probiotics in the last 24 weeks
3. Use of probiotics, other than the study product, during the study period.
4. Antibiotic therapy within the last 4 weeks before inclusion
5. Inflammatory bowel disease
6. Recent (less than 12 weeks) acute myocardial infarction or decompensated heart failure
7. Recent (less than 12 weeks) stroke
8. Known malignancy
9. Inability of the patient to follow the treatment protocol
10. Pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Medical University of Graz

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2020
• Primary Completion (Actual): January 12, 2023
• Study Completion (Actual): March 14, 2023

Study Registration Dates

• First Submitted: July 27, 2020
• First Submitted That Met QC Criteria: October 8, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Actual): March 16, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: probiotics; microbiome; psoriatic arthritis
• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Psoriasis; Arthritis; Arthritis, Psoriatic
• Other Study ID Numbers: 32-347 ex 19/20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No