Probiotics and Palmitoylethanolamide (PEA) for Osteoarthritic Pain and Wellbeing

INTERVENTION: The trial will be an 11 week multiple baseline design with two pathways. Both pathways commence with a baseline (placebo) phase followed by the treatment pathway. As a result there is no washout period between the placebo phase and the treatment phase. Each participant will be assigned to one of two pathways. Pathway 1: Active 1 (Metagenics Ultra Flora Intensive Care) will be taken as one capsule twice daily for 7 weeks AND Active 2 (Bioabsorb PEA) will be taken as one capsule twice daily for 7 weeks. Pathway 2: Active 1 (Metagenics Ultra Flora Intensive Care) will be taken as one capsule twice daily for 9 weeks AND Active 2 (Bioabsorb PEA) will be taken as one capsule twice daily for 9 weeks. Please note that participants will be taking BOTH Active 1 and Active 2 at the same time during the active phases of their respective pathways. Adherence to the intervention ill be through supplement capsule return, verbal questioning at scheduled consultations. During the active phases, participants will take the following: Active 1: Metagenics Ultra Flora Intensive Care (ARTG Entry: 286746) at a dose of one capsule twice daily. Each capsule is 600mg in a clear (00 size Vcap with cream coloured powder) capsule containing Lactobacillus rhamnosus (LGG®) (10 x 109CFU), Saccharomyces cerevisiae (boulardii) (7.5 x 109 CFU) and Bifidobacterium animalis ssp lactis (BB‐12®) (5 x 109 CFU). Active 2: Metagenics Bio Absorb PEA (ARTG Entry: 330607) at a dose of one capsule twice daily. Each capsule is 300mg with a dark green capsule (Vcap with cream coloured powder) containing palmidrol 299.99mg per capsule. Participants will be asked to take this dose (a total of 600mg daily for 6 – 8 weeks) as it represents the minimum ‘loading CONDITION: Alternative and Complementary Medicine ‐ Other alternative and complementary medicine Musculoskeletal ‐ Osteoarthritis Osteoarthritis;Wellbeing; ; Osteoarthritis ; Wellbeing PRIMARY OUTCOME: Difference in mean pain scores between placebo and active phases as measured daily on a 10cm Numerical Rating Scale (NRS)[This will be measured daily from the commencement of the trial (baseline measures in week 1) until the trial conclusion (primary endpoint in week 11).] ; ; This will be conducted at the commencement of the trial and every two weeks thereafter until the completion of the trial (i.e. weeks 1, 3 5, 7, 9, 11). ; ] Difference between placebo and active phases in mean scores of symptoms of functional mobility. Functional mobility will be represented by up to five daily activities nominated by the individual as important in tasks of daily living (Patient Specific Functional Scale (PSFS)). ; ; Each task will be assessed on a 10 cm VAS scale from 0 (indicating no restriction on the activity) to 10 (indicating complete inability to undertake the activity). ; [This will be conducted at the commencement of the trial and every two weeks thereafter until the completion of the trial ; (i.e. weeks 1, 3 5, 7, 9, 11). ] Differences between placebo and active periods in mean scores of personal wellbeing as measured by the Personal Wellness Index (PWI). ; ; This is a scale to assess subjective wellbeing via seven domains: standard of living, health, life achievement, relationships, safety, community‐connectedness, and future security.[This will occur at the commencement of the trial and at the conclusion of the trial (i.e. weeks 1 and 11).] Differences between placebo and active periods in pain location and quality. ; INCLUSION CRITERIA: • Individuals aged between 18 and 85 years • Medical diagnosis or clinical evidence of osteoarthritis in any site • Individuals who describe chronic/symptomatic osteoarthritic pain in the affected joint • In good general health SECONDARY OUTCOME: Changes in medication usage as recorded by the participant's daily usage of analgesic medication in addition to the list of concomitant medications recorded at baseline. [This will be recorded at each clinic visit (scheduled to be every 2 weeks after the commencement of the trial) (i.e. weeks 1, 3 5, 7, 9, 11).] Difference between placebo and active periods for negative emotional symptoms as measured by the total scores on the DASS21. [The DASS 21 is a self‐administered scale of 21 questions that aims to determine perceptions of stress, anxiety and depression. As a shortened version of the original DASS 42 by Lovibond and Lovibond in 1995, the DASS 21 had demonstrated reliability and validity in elderly patients with persistent pain (Wood, Nicholas, Blyth, Asghari, & Gibson, 2010) whilst reducing participant burden as an outcome measure. Of the 21 questions, seven relate to symptoms of depression, seven relate to symptoms of anxiety and the remaining seven relate to symptoms of stress. ; As part of the daily pain diary, participants will be asked to identify pain location(s) by making a mark on the relevant diagram. Participants will also be asked to describe the kind of pain experienced by circling from the following choices: shooting, aching, sharp, dull, burning, throbbing, radiating, gnawing, stabbing, numb and unbearable.[This will be measured daily from the commencement of the trial until its conclusion. ] Patient preference for the treatment condition. ; The patient will be asked to try to identify which were the active and placebo periods during an interview with the practitioner at the end of the trial, before the blinding is broken [This will be conducted at the final clinic visit (i.e. week 11). ] This composite secondary outcome will measure any differences between inflammatory markers (CRP, ESR and fibrinogen) as measured through a blood test pre‐ and post‐intervention. [The blood test will occur at the commencement of the trial and at the conclusion of the trial (i.e. weeks 1 and 11).] This composite secondary outcome will measure serum iron (Kell & Pretorius, 2014) and Vitamin D (Mousa, Misso, Teede, Scragg, & de Courten, 2016) as proxy biomarkers for mood pre‐ and post‐intervention. [This will occur at the commencement of the trial and at the conclusion of the trial (i.e. weeks 1 and 11).] This will be an exploratory outcome measure to explore mechanisms of action for probiotics and PEA in the gastrointestinal system. Differences between placebo and active periods in gastrointestinal markers including zonulin will be measured by a stool analysis. [This will occur at the commencement of the trial and at the conclusion of the trial (i.e. weeks 1 and 11).] • Female participants of childbearing age who agree to continue using birth control measures for the duration of the study