Probiotic for Pain Osteoarthritis

Study Overview
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Brief Summary
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Many people with symptomatic Osteoarthritis (OA) report chronic joint pain, especially if those patients are older than 50 years. In Europe OA is the most common form of chronic pain condition (34%) reported and entails a high economic and social burden for society. Probiotic treatment has been shown to promote bone metabolism, reduce pain and inflammatory responses of age-related musculoskeletal disorders, including OA. Gut microbiota has been proven to be of crucial importance in maintaining human health. However, the microbiota profile changes with aging, while the loss of microbiota diversity and the alterations in the optimal composition and quantity of beneficial microbes are believed to increase the risk of many diseases. Interestingly, emerging evidence leads to the hypothesis that alterations in the gut microbiome could also be considered as possible triggering factors in the onset of musculoskeletal disorders such as OA. We hypothesize that these patients with pain-OA will demonstrate an alteration of the gut microbiota to associated with the intensity of pain.

Official Title
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A Probiotic Intervention on Pain Hypersensitivity and Microbiota Composition in Patients With Pain-osteoarthritis: Study Protocol for a Randomized Controlled Trial

Conditions
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Osteoarthritis of Multiple Joints

Intervention / Treatment
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* Dietary Supplement: Experimental group
* Dietary Supplement: Control group
* Other: Usual medical care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects will have hip or knee OA according on radiographic findings (Kellgren-Lawrence scale ≥3) and who require and eligible for chronic, daily therapy with an NSAIDs to control OA sign and symptoms. A physiatrist (physician) will establish the diagnosis of pain-OA. Exclusion Criteria: Psychiatric or neurological disorders, celiac disease, lactose intolerance, or allergies or other ongoing illnesses (i.e., irritable bowel syndrome, diabetes, ulcerative colitis, etc.) or recent antibiotic treatment (i.e., <3 months before the beginning of the study). Participants with known hypersensitivity to celecoxib, ibuprofen, naproxen, aspirin or esomeprazole, etc. Participants require treatment with aspirin > 325 mg /day. Participants who smoked more than 10 cigarettes per day were excluded. Participants will be excluded also if they score greater than 6 points on the Beck Depression Inventory (BDI) or more than 30 points in the State Trait Anxiety Inventory (STAI), dementia and not Italian speaking due to the high level of language skills required for questionnaires and quantitative sensory testing. Post-traumatic OA (e.g., fractures), congenital hip deformities, surgical interventions to the hip or knee, Legg-Calvé-Perthes disease, or degenerative or non-degenerative neurological conditions in which pain perception is altered will be excluded

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>Probiotic product plus usual medical care (NSAIDs use and the promotion of a healthy lifestyle). | Dietary Supplement: Experimental group<br>* Probiotic (Lactobacillus casei) once daily taken by 6 weeks.<br>Other: Usual medical care<br>* NSAIDs, once daily taken and promotion of a healthy lifestyle by 6 weeks.<br>|
| Placebo Comparator: Control group<br>Sham probiotical plus usual medical care (NSAIDs use and the promotion of a healthy lifestyle). | Dietary Supplement: Control group<br>* Placebo of Probiotic once daily taken by 6 weeks.<br>Other: Usual medical care<br>* NSAIDs, once daily taken and promotion of a healthy lifestyle by 6 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Visual analogue scale (VAS) at 6 weeks |  | Baseline, immediately post-intervention (6 weeks), and follow up (4 weeks) | 
| Change from Pressure Pain Thresholds (PPT) at 6 weeks | PPT will be assessed bilaterally [in the center of the anterior aspect of patella (knee) and the trochanter site (hip)] | Baseline, immediately post-intervention (6 weeks), and follow up (4 weeks) | 
| Change from Inflammatory cytokines at 6 weeks | Fasting serum concentrations of interleukin (IL)-6, tumor necrosis factor (TNF)-α, soluble IL-6 receptor (IL-6sR), soluble IL-1 receptor (IL-1sR), and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assays. | Baseline, immediately post-intervention (6 weeks), and follow up (4 weeks) | 
| Change from Microbiota at 6 weeks | Microbiota composition will be identified through fecal samples for total genomic DNA extraction. The bacteria belonging to Clostridium sensu stricto, Enterobacteriaceae, Escherichia coli, Bifidobacterium, Lactobacillus and yeast were dosed using quantitative PCR approach targeted on 16S rRNA gene | Baseline, immediately post-intervention (6 weeks), and follow up (4 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis, Pain, Microbiota