The aim of this randomized controlled trial is to evaluate the effects of a physiotherapist-delivered dietary weight loss program on clinical outcomes among people with knee osteoarthritis (OA) who have overweight or obesity. The primary hypothesis is that a physiotherapist-delivered dietary weight loss plus exercise program will be more effective in achieving weight loss than a physiotherapist-delivered exercise program alone. Approximately 6-9 physiotherapists in Melbourne, Australia will be recruited and trained in weight management for OA patients, as well as trained in how to deliver the specific study interventions. The same therapists will deliver the intervention in both arms of the trial. 88 participants with knee OA will be recruited from the community and randomized into one of the two arms a) diet plus exercise intervention or b) exercise intervention alone. Participants in both groups will be asked to attend 6 consultations with the physiotherapist over 6 months. Questionnaire and laboratory-based outcome measures will be completed by participants at baseline and at the end of the 6 month intervention period. A biostatistician will analyse blinded, de-identified data.

Clinical guidelines for the management of knee OA recommend exercise as a core treatment for all patients as well as losing weight for those patients who also have overweight/obesity. However, health care systems are frequently under strain often experiencing limited numbers of, and access to, clinicians with specialist weight loss and health behavior change skills. New models of care for OA are needed that support expanded practice roles for clinicians. Physiotherapists are key providers of exercise therapy for knee OA but the effectiveness of physiotherapists to deliver a dietary weight loss program for patients with knee OA is not known.

This study is a randomized controlled trial for which the aim is to evaluate the effects of a physiotherapist-delivered dietary weight loss program in addition to exercise, on weight loss and other clinical outcomes among people with knee OA who have overweight or obesity. The research question is: Is a 6-month physiotherapist-delivered dietary weight loss plus exercise program more effective for improving clinical outcomes than a physiotherapist-delivered exercise program alone in people with knee OA who have overweight or obesity?

Clinical practice guidelines for knee OA recommend patients who have overweight or obesity should lose at least 5-7.5% of body weight. Therefore the study is powered to detect a conservative between-group difference in weight loss of 5% of body weight assuming no change in weight in the control group (exercise only) based on previous research.

A total of 88 participants with chronic knee pain and a clinical diagnosis of knee OA will be recruited from the community. Participants will be enrolled into the study following informed consent and completion of baseline questionnaires and laboratory-based measures. Each participant will be randomly allocated to receive a: a) diet plus exercise program or; b) exercise program alone, over 6 months.

The randomization schedule will be computer generated and prepared by the biostatistician (permuted block sizes 6 to 12) stratified by physiotherapist and sex of participant. The schedule will be stored on a password-protected website maintained by a researcher not involved in either participant recruitment or administration of outcome measures. Group allocation will be revealed to the physiotherapists and the participants by this same researcher following randomisation.

The physiotherapists will undertake comprehensive training prior to being allocated trial participants. Physiotherapists will be trained in weight management, the ketogenic very low calorie diet and trial procedures.

Study participants in both groups will visit a physiotherapist in-person for six individual sessions over 6 months. Participants will choose the therapist according to location. The same therapist will undertake all consultations with any given participant.

Those in the diet plus exercise group will undertake a ketogenic very low calorie diet (VLCD) which has been demonstrated as a safe and effective means of achieving rapid weight loss in the adult population with overweight/obesity. They will receive meal replacements (maximum 2 per day) for up to 14 weeks from the start of the study as well as educational resources. Both groups will also undertake a home-based lower limb muscle strengthening exercise and physical activity program.

A biostatistician will analyse blinded data. Comparative analyses between groups will use intention-to-treat. Multiple imputation will be used to account for missing data if the proportion of missing data is >5%. For the primary outcome, the difference in mean percentage change in body weight will be compared between groups using mixed linear regression model adjusting for baseline weight and the stratification variables, with random intercepts for treating physiotherapist. Similar analyses will be conducted for continuous secondary outcomes. We will also calculate the proportion of participants achieving ≥5% and ≥10% loss of body weight in both groups. For binary outcomes, logistic regression models will be fit using generalized estimating equations, with risk differences and 95% confidence intervals calculated.

Inclusion Criteria:

• Meet the National Institute for Health and Care Excellence [47] clinical criteria for OA: age≥45 years; activity-related knee joint pain; morning knee stiffness ≤ 30 mins
• report history of knee pain ≥ 3 months
• report knee pain on most days of the past month
• report a minimum knee pain score of 4 on an 11-point numeric rating scale during walking over the previous week
• body mass index (BMI) >27 kg/m2
• those using hypertensive medication must be willing to have their blood pressure checked (this can be self-monitoring, at a pharmacist or at a GP) if they feel light-headed or dizzy at any point during the study
• able to give informed consent and to participate fully in the interventions and assessment procedures

Exclusion Criteria:

• weight >150 kgs (due to the added complexities of additional nutritional requirements for individuals above this weight)
• inability to speak English
• on waiting list for/planning knee/hip surgery or bariatric surgery in next 6 months
• arthroplasty on affected knee
• recent knee surgery on affected knee (past 6 months);
• self-reported inflammatory arthritis (e.g. rheumatoid arthritis)
• weight loss of > 2 kg over the previous 3 months
• already actively trying to lose weight by any of the following mechanisms:using meal replacements for weight loss; being a member of a slimming club (e.g. weight watchers); receiving support from another health care professional for weight loss; using any drugs prescribed to aid in weight loss; using structured meal programs for weight loss such as 'Lite n' Easy'
• unwilling to continue current dietary patterns if randomized to exercise only group
• unable to undertake ketogenic VLCD for medical reasons including self-reported: diagnosis of Type 1 diabetes;Type 2 diabetes requiring insulin or other medication apart from metformin; Warfarin use; stroke or cardiac event in previous 6 months; unstable cardiovascular conditions; fluid intake restrictions; renal (kidney) problems (unless clearance is obtained from a general practitioner (GP), including GP confirmation that estimated glomerular filtration rate >30 mL/min/1.73m2); any neurological condition affecting lower limbs; vegan dietary requirements due to complexity of delivering a nutritionally complete diet within the ketogenic diet regime

IPD can be shared

We will share all data that support results of the trial following publication. Additional data that have not been published will be withheld until at least six months after publication.

Data will be made available as required for specific, approved analyses. Data will be provided from locked, cleaned, and de- identified study database. All requests for data sharing will be reviewed by the Principal Investigator to ensure no conflict with any planned sub analyses and to ensure that the data are shared in an ethical and protected manner. Analyses for non-commercial purposes are eligible. Before any analysis, a signed Confidentiality Agreement and/or Data Sharing Agreement is required.

The components of each treatment arm will be disclosed to participants as we wish to test the interventions under real world conditions whereby consumers are fully informed about the nature of the components before choosing whether or not they wish to participate. The research staff collecting non-self-reported outcome measures (including the primary outcome) will be blinded to group allocation. The staff member collecting laboratory measures at 6 months will be different to the staff member who collects the baseline data. It is not possible to blind physiotherapists as they are providing interventions to both trial arms (in order to ensure physiotherapist-related factors such as personality, clinical practice experience etc are similar across groups and cannot confound results). The person performing the statistical analyses will be blinded.