Probiotic for Pain Osteoarthritis

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

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.

Study Overview

• Status: Unknown
• Conditions: Osteoarthritis of Multiple Joints
• Intervention / Treatment: Dietary supplement: Experimental group; Other: Usual medical care; Dietary supplement: Control group

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jorge H Villafañe, PhD; Phone Number: +39 3395857563; Email: mail@villafane.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Fondazione Don Carlo Gnocchi Onlus
• Investigators: Principal Investigator: Jorge H Villafañe, PhD, Fondazione Don Carlo Gnocchi Onlus

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2019
• Primary Completion (Anticipated): January 1, 2020
• Study Completion (Anticipated): July 1, 2021

Study Registration Dates

• First Submitted: May 25, 2019
• First Submitted That Met QC Criteria: May 29, 2019
• First Posted (Actual): May 30, 2019

Study Record Updates

• Last Update Posted (Actual): May 30, 2019
• Last Update Submitted That Met QC Criteria: May 29, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Osteoarthritis; Pain; Microbiota
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis
• Other Study ID Numbers: Microbiota-PainOA

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