The (cost-)effectiveness of a combined lifestyle intervention in overweight and obese patients with knee osteoarthritis in primary care

Knee osteoarthritis (OA) is a chronic condition characterized by pain and
impaired function and strongly contributes to physical disability. With an
aging population, the prevalence of OA is estimated to be the number one
chronic disease in the Netherlands in 2040. A high BMI is a major risk factor
for knee OA, but also considered the most modifiable risk factor for knee OA..
In those with established knee OA in secondary care, there is evidence that
weight loss has notable effects on pain and function. Many international
guidelines therefore recommend 5 to 10% weight loss for knee OA patients if
overweight or obese.

The importance of a healthy lifestyle for people with overweight has received
considerable attention. What is not yet clear is the effect of sex- and gender
on making lifestyle choices, the preference for a lifestyle program, or
adherence to a lifestyle program. In addition, weight loss in women might have
different effects on knee OA development and/or progression than weight loss in
men. These differences between men and women must be considered to improve
health care.

In the Netherlands, a combined lifestyle intervention (i.e. beweegkuur) was
developed in 2007 by the Netherlands Institute for Sport and Physical Activity,
commissioned by the Dutch ministry of Health, Welfare and Sports, with the aim
to treat and prevent diabetes mellitus type 2. Further development and
refinement made the beweegkuur available for patients with overweight and
obesity. However, it is only since 2019 that it is possible for GPs to refer
eligible patients to a combined lifestyle intervention (e.g. *Beweegkuur*,
*Slimmer*, Cool*). Eligible for referral are patients that have overweight or
obesity and additional risk factors for cardiovascular diseases, diabetes type
2, or presence of sleep apnea or OA. Participation is only possible with a
referral by the GP or medical specialist. The costs for the combined lifestyle
intervention are for eligible patients since 2019 covered by the basic health
insurance that all Dutch inhabitants have.

However, the (cost-)effectiveness of this intervention in the OA target
population and in the primary care in the Netherlands has not yet been
investigated. Therefore, the main aim of the described project is to
investigate the (cost-)effectiveness of a combined lifestyle intervention in
early knee OA patients in primary care. The search for (gender- and
sex-related) factors that may mediate the effects of diet and exercise on
clinical and structural outcomes will help to optimize and design optimal
effective interventions where mechanisms of action are targeted.

The general aim of this project is to determine the clinical and
cost-effectiveness of a combined lifestyle intervention, in addition to usual
care, in early stage knee OA patients with overweight/obesity in comparison
with usual care.

Primary Objective:
1. To determine the effectiveness of a lifestyle intervention in primary care
in early stage knee OA patients with overweight/obesity on the mechanistic
outcome weight loss after 24 months.

Secondary Objective(s):
1. To determine the cost-effectiveness of a lifestyle intervention compared to
usual care in primary care in knee OA patients with overweight/obesity after 24
months from a societal perspective
2. To determine the effectiveness of a lifestyle intervention in primary care
in early stage knee OA patients with overweight/obesity on the clinical and
structural progression of knee OA after 24 months
3. To explore potential working mechanisms for the change in both clinical and
structural features of knee OA within a 24 month time frame
4. To determine whether a lifestyle intervention in an OA population has
positive side effects on HbA1c level (diabetes mellitus), cardiovascular risk
factors (cholesterol, blood pressure and kidney function), and the intestinal
microbiota after 24 months.

A pragmatic randomized controlled trial (RCT) among patients with early signs
of knee OA in general practice and a Body Mass Index (BMI) >=25 kg/m2 with a
follow-up of 24 months. Participants are randomized to either a lifestyle
intervention program + usual care or usual care alone.

Randomisation:
The randomization sequence will be determined by an independent researcher from
the department, with the use of a computer generated randomisation list. This
sequence is secret for all involved researchers of the study. When patients are
eligible for inclusion and completed the informed consent procedure, the
baseline measurement takes place. Hereafter, the patients will be randomly
allocated to one of the two groups by a researcher:
1) Usual care + combined lifestyle intervention
2) usual care alone

Procedures:
If the patient fulfils the inclusion criteria after prescreen and is willing to
participate, he or she will be sent a written informed consent form and a
baseline questionnaire by email.
After written consent the patients will be invited for a baseline visit for
physical examination (including blood collection) and a Magnetic Resonance
Imaging (MRI) of the symptomatic knee. Patients will be asked to collect a
fecal sample in a collection tube and hand the sample in during the baseline
visit.

Following the baseline assessments, the patients will be randomized (refer to
above) into two groups.

All participating patients will be sent 3-monthly questionnaires and after 24
months follow-up all will be asked to collect a fecal sample and will be
invited again for a physical examination and MRI of the knee.

Following the 2-year intervention, 30 patients will be invited to participate
in qualitative interviews. All the interviews will be audiotaped and
transcribed verbatim.

All participants will be asked for consent to contact them again after this
study period since we additionally aim for a long-term follow-up (follow-up
after the two-year intervention terminated) of this patient population.

All patients will receive usual care by their GP following the NHG guideline
non-traumatic knee complaints. This includes advice for regular physical
activity (at least 30 minutes a day) and advice to lose weight if the patient
has a BMI>=25 kg/m2. Moreover, pain medication is considered and patients may be
referred to a physical therapist when they fail to get enough exercise
themselves.

Patients randomized to Arm 1, the intervention group will, in addition to usual
care, be referred to a certified lifestyle coach for the *Gecombineerde
Leefstijl Interventie* (Beweegkuur-GLI).

Combined lifestyle intervention:
The Beweegkuur-GLI has three primary aims
1. Exercise: encouragement towards physical activity and/or increase physical
activity
2. Nutrition: Decrease energy intake by an individual diet, that will lead to
an improvement of eating behaviour
3. Behavioural change: Support of self-management in lifestyle changes
During the entire trajectory, participants will be supported by a team of
health care professionals, in which the lifestyle coach has the central role.
Next to the lifestyle coach, there is involvement of a physical therapist,
dietician, a neighbourhood sport coach and possible local sport services.
The general aim of the Beweegkuur-GLI is to lose at least 5% of body weight
during the first year and to maintain this weight loss in the second year.

Support of self-management:
Within the Beweegkuur-GLI, self-management is seen as the individual ability of
the participant to deal with symptoms, physical, psychological and social
consequences of a weight related health risk and to adjust their lifestyle of
this. The degree of self-management is different for every participant of the
program. The general model self-management guides the lifestyle coach on how to
support the participant.

Support and coaching (Motivational Interviewing (MI)):
MI forms an essential part of the Beweegkuur-GLI and is defined as a directive
person-centred support style in order to stimulate a change of behaviour by
ambivalence compared to help to clarify and solve changes. The essence of MI is
that the motivation for change comes from the participant itself instead of
from the health care professional. The lifestyle coach will use the stages of
change model, including the five motivational stages, as a core guidance.

Lifestyle coaching:
The Beweegkuur-GLI starts with an individual intake with the lifestyle coach,
followed by seven individual sessions of 30 minutes in the first year of the
program. Bi-weekly group sessions are scheduled in the second quarter of year
one.
During year two, five individual sessions are scheduled with the lifestyle
coach.

Exercise component:
The physical therapist will, during an individual session, set up an individual
exercise program at the start of the program. Additionally, two group sessions
will take place in the first quarter of year 1, that aim to stimulate physical
activity and discusses the aims and goals, including the stimulation to
continue the physical activities after this period within the local sport and
physical activity services. During year two there is continued coaching of the
community sport coach or physical therapist.

The general aim of the exercise component is to reach a minimum of 1200
kilocalories energy expenditure per week, but optimally 2000 kcal/week. A
gradual increase towards this dose is seen as most effective. There is a
specific manual for physical therapists working with the Beweegkuur-GLI
(*Document BeweegKuur voor de fysiotherapeut*) that leads physical therapist to
all phases and decisions.

Nutrition component:
The dietician delivers the nutritional support and the lifestyle coach takes
care of the follow-up on the advices of the dietician. The nutritional advices
are provided following:
• NDF (Dutch Diabetes Federation) nutrition guidelines (2015) for diabetes
patients
• Guideline Diagnostics and treatment of obesity in adults with a BMI>30
• Guidelines healthy nutrition as formulated by the Dutch Health Council for
adults with a BMI >=25 and <=30
The program consists of individual consultations with the dietician and group
education. All participants start with an individual session at the dietician
and three group sessions during the first year. The content of the individual
session, that will take place in the first quarter of year one, consist of
extensive diagnostics, formulate a joint plan of treatment (participation in
group sessions, maximum of 3 hours of follow-up consultations, individual
diet), information on nutrition and behaviour that relates to OA. The three
group education sessions (60 minutes, maximum of 12 participants) are planned
in the first year. These primarily focus on increase of knowledge, improvement
of skills, deal with high risk situation, control eating behaviour and contact
with other patients. There is a specific manual for dieticians working with the
Beweegkuur-GLI (*Document BeweegKuur voor de diëtist*) that leads dieticians to
all phases and decisions. The lifestyle coach will be accompanying the
dietician at the first group session. In year two, another three group sessions
(60 minutes) will take place with the dietician.

All patients will receive care as usual provided by the general practitioner,
so no changes in outcomes are expected in the control group, compared to normal
subjects not participating in this study.

The patients allocated to the intervention group are likely to benefit of the
intervention: A systematic review showed that 5 to 10% weight loss produces
small positive effects on pain, self-reported disability and quality of life in
adults with mild to moderate knee OA.

The burden for all patients participation in this study is the time needed to
fill in the 9 questionnaires (baseline approximately 10-15 minutes, follow-up
each approximately 5-10 minutes), collection of fecal samples (each
approximately 5 minutes), and two examinations including a physical
examination, blood samples and MR Imaging of the knee.
Each examination will take approximately 1 hour.

30 patients will participate in the semistructured interviews, therefore the
burden of participation will be higher. The interviews will take a maximum of
60 minutes. Depending on the patient's preference, interviews will be conducted
face-to-face in the Erasmus MC, at the patient's home, or online.