Effect of Probiotic Supplements on Osteoarthritis Outcomes

Knee Osteoarthritis Clinical Trial

— ProOA23  

Official title:

Effect of 6 Months Probiotic Supplement on Pain, Function, Quality of Life and Inflammation in Females With Knee Osteoarthritis: A Double-blinded Randomized Placebo-controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06459700
• Other study ID #: ProOA23
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 15, 2024
• Est. completion date: April 30, 2027

Study information

• Verified date: June 2024
• Source: Lund University
• Contact: Anna Cronström, PhD
• Phone: +46462224965
• Email: anna.cronstrom[@]med.lu.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

Aim:

To investigate the effect of 6-moths 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-score difference in KOOS-12 with 80% power and α 0.05, 72 participants (36 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, Jessica Neilands, PhD, Associate Professor, Science manager, Probi AB, Lund, Sweden and Daniel Benoit, PhD, senior lecturer in Experimental Health Sciences at Lund University, Sweden.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 86
• Est. completion date: April 30, 2027
• Est. primary completion date: April 30, 2027
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 45 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Dietary Supplement:
• Probiotic supplements/placebo supplement
See arm/group description

Locations

Country	Name	City	State
Sweden	MoReLab, Lund University	Lund

Sponsors (2)

Lead Sponsor	Collaborator
Lund University	Probi AB

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Kinematics assessed with 3D motion analysis	Comparison of the probiotic group with the placebo group in terms of changes from baseline and 6-month follow-up in Kinematics (joint angles in degrees) during the functional tasks	6 months
Other	Kinetics assessed with 3D motion analysis and force plates	Comparison of the probiotic group with the placebo group in terms of changes from baseline and 6-month follow-up in kinetics (joint moments (newton meter)) during the functional tasks.	6 months
Other	Intestinal barrier integrity	Comparison of the probiotic group with the placebo group in terms of changes from baseline and 6-month follow-up a molecular biomarker for intestinal barrier integrity (Zonulin)	6 months
Primary	Knee injury and Osteoarthritis Outcome Score (KOOS)-12	Change in the KOOS-12 (total score) from baseline to 6 months in the probiotic group compared with the placebo group. The KOOS-12 is scored from 1-100 (worst-best) scale.	6 months
Secondary	Knee injury and Osteoarthritis Outcome Score (separate subscale score)	Comparison of the probiotic group with the placebo group in terms of changes from baseline to 3-month and 6-month follow-up in Scores on the separate subscales (pain, symptoms, activity of daily living, sport/recreation and knee-related quality of life) from the full KOOS questionnaire. The KOOS is scored from 1-100 (worst-best) scale.	3 to 6 months
Secondary	Visual Analogue Scale (VAS)	Comparison of the probiotic group with the placebo group in terms of changes from baseline to 3-month and 6-month follow-up in VAS scores (pain severity), assessed on an ordinal scale from 0 to 10 where 0 indicates no pain and 10 worst possible pain the last week	3 to 6 months
Secondary	Work Productivity and Activity Impairment questionnaire (WPAI)	Comparison of the probiotic group with the placebo group in terms of changes from baseline to 3-month and 6-month follow-up in WPAI. The WPAI questionnaire includes 6 questions regarding employee's absenteeism, reduced job performance, work productivity loss, and activity impairment. WPAI outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes.	3 to 6 months
Secondary	Patient Acceptable Symptom State (PASS)	Comparison of the probiotic group with the placebo group in terms of changes from baseline to 3-month and 6-month follow-up in PASS. The PASS involves a question regarding if the patient is satisfied with their current knee function with to response options (yes/no)	3 to 6 months
Secondary	Pain-relieving medication intake	Comparison of the probiotic group with the placebo group in terms of changes from baseline to 3-month and 6-month follow-up in pain-relieving medication intake. Here the patients reports the type and dosage of any medication	3 to 6 months
Secondary	Wish for surgery	Comparison of the probiotic group with the placebo group in terms of changes from baseline to 3-month and 6-month follow-up in wish for surgery. The patients are asked if they wish to undergo surgery due to their knee problems (yes/no).	3 to 6 months
Secondary	40m fast paced walk test	Comparison of the probiotic group with the placebo group in terms of changes from baseline and 6-month follow-up in 40m fast paced walk test, assessed as time taken to walk 4x10 meter as fast as possible	6 months
Secondary	30 seconds sit to stand test	Comparison of the probiotic group with the placebo group in terms of changes from baseline and 6-month follow-up in the 30 seconds sit to stand test, assessed by the number of repetitions of sitting to standing from a chair during a period of 30 second.	6 months
Secondary	Stair climb test	Comparison of the probiotic group with the placebo group in terms of changes from baseline and 6-month follow-up in the stair climb test, assessed as time taken to ascend and descend a flight of 5 stairs.	6 months
Secondary	3 minute walk test	Comparison of the probiotic group with the placebo group in terms of changes from baseline and 6-month follow-up in the 3 minute walk test, assessed as distance walked during 3 minutes on a treadmill.	6 months
Secondary	Molecular biomarkers for cartilage degeneration and inflammation.	Comparison of the probiotic group with the placebo group in terms of changes from baseline and 6-month follow-up in molecular biomarkers for cartilage degeneration and inflammation.	6 months