Dysbiosis of the gut microbiota is believed to contribute to the development and progression of osteoarthritis (OA), suggesting a role for probiotics in the treatment of OA. Animal studies have shown that certain probiotic strains decrease the inflammatory responses, pain sensitization and OA progression. There are, however, few clinical studies in humans to support this. In this double-blinded randomized controlled trial we will investigate the effect of 6-months probiotic supplements compared to placebo on OA related outcomes in females with diagnosed knee OA.

Aim:

To investigate the effect of 6-months probiotic supplements compared to placebo on OA related outcomes in females with diagnosed knee OA.

Design: Double-blinded randomized placebo controlled trial

Study arms: One treatment arm will receive probiotic supplement in opaque white capsules and the other treatment arm will receive identical opaque placebo capsules. The placebo product will contain maize starch powder. Study participants will take one capsule daily for six months.

Statistical analysis Main outcome: The independent T-test will be used to evaluate group differences in change in KOOS-12 scores between baseline and 6-months follow-up, given that all assumptions for parametric tests are satisfied. If assumptions are not met or if there are differences in baseline characteristics due to imbalanced randomization the Mann-Whitney U-test or regression analysis will be used as appropriate.

Secondary and explorative outcomes: The independent T-test (continuous, normal distributed data), the Mann-Whitney U-test (ordinal, non-normally distributed data) and cross-tabulations with Chi2 test (nominal data) will be used to evaluate differences in secondary and explorative outcomes between the two groups.

Estimated enrollment: 86 participants. Based on the ability to detect a 10-point difference in KOOS-12 with 80% power and α 0.05, 70 participants (35 per arm) will be needed. With an approximate drop-out rate of 20% from baseline to follow-up, 86 participants will be recruited.

Investigators: Eva Ageberg, PT, PhD, Professor in physical therapy, Lund University, Sweden (Principal investigator), Anna Cronström, physical therapist, PhD, Lund University, Sweden and Jessica Neilands, PhD, Associate Professor, Science manager, Probi AB, Lund, Sweden.

Inclusion Criteria:

1. Females aged 45-70 years
2. Clinical diagnosis of knee OA
3. Mild to moderate knee joint pain (Visual Analog Scale (VAS) 3-7)) during the last 3 months
4. Able to perform walking and stair tests
5. No use of other supplements/food products containing probiotics and/or supplements targeting OA symptoms (e.g., glucosamine, turmeric)
6. Able to write and understand Swedish.

Exclusion Criteria:

1. Rheumatoid arthritis or other active generalised inflammatory comorbidities affecting the gastrointestinal tract (IBD, celiac disease)
2. Performed a total knee replacement on the affected knee or on waiting list for joint replacement
3. Other concomitant injuries or surgeries overriding the OA knee symptoms
4. Other concomitant injuries or diseases where physical activity is a contra indication
5. Malabsorption disorders, presence of renal and/or hepatic failure
6. Use of corticosteroids with doses above 10 mg/day and/or Intra-articular injections during the previous 6 months
7. Heavy use of alcohol (>10 standard units a week), or recreational drug use
8. BMI ≥30 Kg/m2
9. Antibiotic treatment during the previous 2 months
10. clinical depression diagnosis
11. Pregnancy/breast feeding
12. Smoking or other nicotine containing products during the previous 6months
13. Performed a gastric bypass
14. Immunosuppressive treatment or impaired immune system
15. Chronic or acute diarrhoea
16. Blood/plasma donation/transfusion during the 3months or during the study
17. Non-controlled diabetes
18. Allergy with regards to any of the study product ingredients.

Plan description: De-identified IPD for primary and secondary outcomes will be made available upon reasonable request.

Statistical analysis plan will be published in a study protocol before completion of the analysis.