Intensive Diet vs Knee Arthroplasty for Knee Osteoarthritis

The Oxford Knee Score (OKS) is a 12-item Patient Reported Outcome questionnaire developed specifically to assess the patient's perspective on the outcomes of KA with respect to combined pain and physical function. Standardized answer options are given (5 Likert boxes) and each question is assigned a score from 0 to 4. Thus, a total score is calculated that ranges from 0 and 48, with 48 indicating the best outcome. The OKS is short, practical, reliable, valid, and sensitive to clinically important changes over time.

EQ-5D-5L is a standardized patient-reported instrument for use as a measure of health outcome and quality of life. EQ-5D-5L is designed for self-completion by respondents and is ideally suited for use in surveys.

The EQ-5D-5L consists of a descriptive system and the EQ Visual Analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Standardized answer options are given (5 Likert boxes) and each question is assigned a score from 1 to 3.

A country-specific index score is calculated.

Metabolic Syndrome (MetS) is defined according to the Harmonized definition: MetS is present when three or more of the following conditions occur simultaneously:

• Elevated waist circumference (≥94 cm in men and ≥80 cm for women)
• Elevated triglycerides (drug treatment for elevated triglycerides is an alternate indicator) ≥150 mg/dL (1.7 mmol/L)
• Reduced HDL-C (drug treatment for reduced HDL-C is an alternate indicator) <40 mg/dL (1.0 mmol/L) in males; <50 mg/dL (1.3 mmol/L) in females
• Elevated blood pressure (antihypertensive drug treatment in a patient with a history of hypertension is an alternate indicator) Systolic ≥130 and/or diastolic ≥85 mm Hg
• Elevated fasting glucose (drug treatment of elevated glucose is an alternate indicator) ≥100 mg/dL

At clinical outcome assessment visit, the participants will be interviewed by an investigator about their use of analgesics since last visit. The interview will be focused on intake of

• Paracetamol/acetaminophen
• NSAIDS
• Acetylic acids
• Opioids The use of these analgesics will be recorded as use/non-use

KOOS-12 is a 12-item measure derived from the original 42-item Knee injury and Osteoarthritis Outcome Score. KOOS-12 provides scores for knee-specific Pain, Function and QOL, along with a summary measure of overall knee impact. KOOS-12.

Each item is scored from 0 to 4, left to right, with 0 representing no knee problems and 4 representing extreme knee problems. The KOOS-12 Summary knee impact score is calculated as the average of the Pain, Function and QOL scores that are calculated on a 0-100 scale, where 0 is the worst possible and 100 is the best possible score.

The participant's assessment (PGA) of the impact of their knee on everyday life is measured as the response to the question "Taking into account all the activities you have during your daily life, your level of pain, and your functional impairment, how much does your [left/right] knee impact your daily life?". A 100 mm visual analogue scale (VAS) will be used as assessment instrument with anchors: 0 = "No impact" and 100 = "Worst imaginable impact".

The timed up-and-go test (TUG) is a physical performance test primarily measuring the participants' ability to turn whilst walking (ambulatory transitions).

The TUG measures the time it takes a participant to rise from a standard armchair, walk as quickly, but as safely as possible, a distance of 3 m, turn, walk back to the chair and sit down. Usual footwear and regular walking aids are allowed and recorded. The fastest of two trials is recorded in seconds. The same chair is used for all tests in this trial.

PASS is assessed as yes/no answer to the question: "Taking into account all the activities you have during your daily life, your level of pain, and also your functional impairment, do you consider that your current state is satisfactory?".

Those who reply 'no' the PASS question will be asked to answer (yes/no) the following question: "Would you consider your current state as being so unsatisfactory that you think the treatment has failed?" Participants replying, 'yes' to this second question will be defined as experiencing 'treatment failure' (TF).

Besides the above algorithm treatment failure (TF) is also reached for:

• Participants in the KA group that during the observation period undergo revision surgery, And,
• Patients in the intensive diet group that during the observation period chose to undergo knee surgery.

A global transition questionnaire in which patients are asked to rate how they experience their health status has changed since before a treatment.

The participants answer the question "How do you experience your knee problems now compared to prior to your study participation? Predefined answers are provided with scores ranging from -3 (worsening) to 3 (improvement):

• 3: Worse, an important deterioration
• 2: Somewhat worse, but enough to be an important deterioration
• 1: Very small change, not enough to be an important deterioration 0: About the same

• Very small change, not enough to be an important improvement
• Somewhat better, but enough to be an important improvement
• Better, an important improvement

From the transition scores, a predefined cut-off to define participants who experience minimally important improvement is set to a score of at least 2.

Per the Outcome Measures in Rheumatology (OMERACT) and Osteoarthritis Research Society International (OARSI) - (OMERACT-OARSI) criteria, a participant is classified as a (positive) responder if at least one of the following two conditions is observed at the post-Baseline assessment:

• In either KOOS-12 pain subscale or KOOS-12 function subscale, both a > 50% improvement from Baseline and an absolute change from Baseline of > 20 units (0-100 scale),

OR Improvement in at least two of the following three:

• Improvement in KOOS-12 pain subscale of > 20% improvement from Baseline and an absolute change from Baseline of > 10 normalized points (0-100 scale)
• Improvement in KOOS-12 function subscale defined as > 20% improvement from Baseline and an absolute change from Baseline of > 10 normalized points (0-100 scale)
• Improvement in PGA defined as > 20% improvement from Baseline and an absolute change from Baseline of > 10 mm (0-100 mm scale)

The participants body weight is measured using a calibrated digital scale. The measurement is taken in kilograms (kg) recorded with 1 decimal.

Measurement of step counts will be done using wrist-worn activity trackers designed to measure steps (step counter). The participants will be asked to wear the step counter on the non-dominant wrist continuously (24 hours/day) for a 7-day period.

Glucose will be measured from fasting blood samples

HbA1c will be measured from fasting blood samples

Plasma lipids will be measured from fasting blood samples

Systolic and diastolic blood pressures are measured using a standard blood pressure apparatus.

Body composition as well as bone mineral measurements will be assessed via whole-body dual energy X-ray absorptiometry (DEXA) using a Norland scanner. From the same scan, the following parameters will be recorded; fat mass (kg), lean body mass (kg).

Brief Illness perception questionnaire (B-IPQ) is a generic 8-item questionnaire developed to rapidly assess the cognitive and emotional representations in a variety of illnesses.

Five of the items assess cognitive illness representations; two of the items assess emotional representations; and one item assesses illness comprehensibility.

Each item is scored on a 4 point Likert scale (0-3) with higher scores indicating worse illness perception. No sum score is calculated.