Probiotic for Osteoarthritis

Deciphering the Role of the Microbiota in Osteoarthritis for Improving Therapy

The gut microbiome appears to be a significant contributor to musculoskeletal health and disease. Microbiome composition and its functional implications have been associated with prevention of bone loss and/or reducing fracture risk. Genetic background, gender, dietary intake, and social factors are also important factors which contribute to the musculoskeletal health, as well as to the normal balance of intestinal microbiota. The link between gut microbiota and joint inflammation in murine models of arthritis has been established, and it is now receiving increasing attention in human studies. Recent papers have demonstrated substantial alterations in the gut microbiota in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). These alterations resemble those established in systemic inflammatory conditions (inflammatory bowel disease, spondyloarthritides, psoriasis), which include decreased microbial diversity and lower abundances of bacteria belonging to the Firmicutes phylum that are known to have immunoregulatory properties.These new findings open important future horizons both for understanding disease pathophysiology and for developing novel biomarkers and treatment strategies. Further investigation into the mechanisms linking changes in the microbiome to alterations in bones and joints is necessary. Next Generation Sequencing, metatranscriptomic analysis, and metabolomic approaches may provide yet-greater insight and help further understand these mechanisms. To investigate gut microbiota change will be associated with the sintoms of knee and / or hip OA in italian patients.

Study Overview

• Status: Unknown
• Conditions: Osteoarthritis of Multiple Joints
• Intervention / Treatment: Other: Probiotic product

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

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

Study Locations

• Italy
  • Milan, Italy, 10045
    • Jorge Hugo Villafañe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All subjects will have hip or knee OA according on radiographic findings (Kellgren-Lawrence scale ≥3). 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 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotcal group; Probiotic (Lactobacillus casei) once daily taken by 3 months	Other: Probiotic product; Probiotic (Lactobacillus casei) once daily taken by 3 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Pain Intensity at 3 months.	Visual Analogue Scale, 0: no pain, 100: maximum pain	Baseline, immediately post-intervention (3 months).
Change from range of Pressure Pain Thresholds at 3 months	Algometry, will be assessed bilaterally [in the center of the anterior aspect of patella (knee) and the trochanter site (hip). The range of values of the pressure algometer was 0 to 10 kg.	Baseline, immediately post-intervention (3 months).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from concentrations of Inflammatory cytokines at 3 months.	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. All samples were measured in duplicate, and the average of the two values was used for data analyses.	Baseline, immediately post-intervention (3 months).
Change from Microbiota at 3 months.	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 (3 months).

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): February 1, 2020
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): July 1, 2022

Study Registration Dates

• First Submitted: June 10, 2019
• First Submitted That Met QC Criteria: June 13, 2019
• First Posted (Actual): June 14, 2019

Study Record Updates

• Last Update Posted (Actual): June 14, 2019
• Last Update Submitted That Met QC Criteria: June 13, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Osteoarthritis; Microbiota; Probiotic
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis
• Other Study ID Numbers: Probiotic in OA

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