Clinical trial NCT04645732: Personalized Exercise Therapy and Self-management Support for Patients With Multimorbidity
Official title: Improving Health in People With Multimorbidity: a Paradigm Shift in Health Care From Disease-based Curative Models to Personalized Exercise Therapy and Self-management
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Osteoarthritis, Knee
Osteoarthritis, Hip
Heart Failure
Coronary Heart Disease
Hypertension
Type2 Diabetes
Chronic Obstructive Pulmonary Disease
Depression
Keywords: Exercise
Self-management
Clinical Trial
Multimorbidity
Evaluation
Lead sponsor: University of Southern Denmark
Sponsor class: OTHER
Collaborators: name: Naestved Hospital
name: Slagelse Hospital
name: Lolland Municipality
name: Roskilde Municipality
name: Psychiatric Hospital West, Slagelse
name: Næstved, Slagelse and Ringsted Hospitals' Research Fund
name: Association of Danish Physiotherapists
name: The Danish Health Confederation through the Development and Research Fund
name: European Research Council
name: Holbaek Sygehus
name: Nykøbing Falster County Hospital
name: FysioDanmark Holbæk
name: Zealand University Hospital
name: Lægerne Reventlow og Wolfhagen, Slagelse
name: Lægerne Algade 17, Roskilde
First posted: 2020-11-27
Enrollment: 228
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The RCT is a pragmatic, parallel-group, superiority RCT (1:1 ratio)
Primary purpose: TREATMENT

Brief summary: Chronic conditions such as knee or hip osteoarthritis (OA), chronic obstructive pulmonary disease (COPD), heart failure (HF), coronary heart disease (CHD), hypertension, type 2 diabetes mellitus (T2DM) and depression are among the leading causes of global disability and affect hundreds of millions of people around the world. In recent years, multimorbidity, commonly defined as the co-occurrence of at least two chronic conditions, has also gained interest due to its substantial impact on the person and society.

Despite the significant burden of multimorbidity, little is known about how to treat this effectively. A 2016 Cochrane systematic review found that interventions targeting populations with specific combinations of conditions and addressing specific problems such as functional difficulties may be more effective. Exercise therapy is a treatment addressing functional limitations that is a safe and effective treatment of at least 26 chronic conditions, including OA, HF, CHD, hypertension, T2DM, COPD and depression. Furthermore, self-management support is increasingly recognized as an essential component of interventions to improve outcomes in patients living with multimorbidity and to support the long-term adherence to exercise. A new systematic review found that exercise seems effective in people with multimorbidity (the conditions included in the current study), however highlighting the need for further high-quality RCTs.

The aim of this randomized controlled trial (RCT) is to investigate the effects of a personalized exercise therapy and self-management support program in addition to usual care on self-reported, objectively measured and physiological outcomes in people with multimorbidity (i.e. at least two of the following conditions: OA (knee or hip), heart condition (HF or CHD), hypertension, T2DM, COPD and depression). The primary endpoint is 12 months, but 4- and 6-month follow-ups are included as well and a 12-month health economic evaluation of the program will be conducted.

Prior to the RCT, a feasibility trial of 20 people with multimorbidity, all undergoing the personalized exercise therapy and self-management support program, will be conducted using the same methods as in the RCT, but primarily focusing on feasibility outcomes (recruitment, retention, adherence to treatment, burden of outcomes, improvements in outcomes, adverse events). This will start recruitment in Feb 2021 and end August 2021.

The MOBILIZE project has received funding from several foundations, including the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 801790).

Detailed description: Chronic conditions such as knee or hip osteoarthritis (OA), chronic obstructive pulmonary disease (COPD), heart failure (HF), coronary heart disease (CHD), hypertension, type 2 diabetes mellitus (T2DM) and depression are among the leading causes of global disability and affect hundreds of millions of people around the world. In recent years, multimorbidity, commonly defined as the co-occurrence of at least two chronic conditions, has also gained interest due to its substantial impact on the person and society. In general, multimorbidity affects more than half of all people with chronic conditions. Two out of three people with OA have comorbidities, with HF, CHD, hypertension, T2DM, COPD and depression being some of the most common.

People with multimorbidity account for 78% of all consultations in primary care and multimorbidity is associated with poorer function and quality of life, depression, intake of multiple drugs and increased health care utilization, with some studies demonstrating an almost exponential relationship between the number of chronic conditions and their health care costs. Furthermore, we know from qualitative research that treating one condition at a time is inconvenient, inefficient and unsatisfactory for the person with the chronic conditions and his or her health care provider. Most research so far has excluded people with multimorbidity, due to its focus on only one specific condition, and most of the health care sector manages each individual condition on its own instead of the person, highlighting the negative impact of the current disease-based curative models on multimorbidity. With a population that is ageing, and a significant number of people with multimorbidity being younger than 65 years of age, the proportion of people with multimorbidity is increasing rapidly, emphasizing the need to take action to deal with the increasing burden of chronic conditions and multimorbidity through treatment and prevention.

Identifying and developing effective and affordable treatment strategies to deal with the global burden of chronic conditions and multimorbidity is a major focus of modern health care around the world. Despite the significant burden of multimorbidity, little is known about how to treat this effectively. A 2016 Cochrane systematic review found that interventions targeting populations with specific combinations of conditions and addressing specific problems such as functional difficulties may be more effective. A treatment addressing functional limitations that is able to improve symptoms in at least 26 chronic conditions, including OA, HF, CHD, hypertension, T2DM, COPD and depression is readily available. This treatment is exercise therapy, which is effective, safe and supported by substantial evidence in patients with knee and hip OA, HF and CHD, hypertension, T2DM, COPD, depression and a range of other chronic conditions. A new systematic review found that exercise seems effective in people with multimorbidity (the conditions included in the current study), however highlighting the need for further high-quality RCTs. Furthermore, self-management support is increasingly recognized as an essential component of interventions to improve outcomes in patients living with multimorbidity. There is increasing evidence that effective management of multimorbidity requires the active participation by patients in the care process. Self-management support interventions have been shown to change health behaviors, improve health status, and reduce health care utilization and costs. Self-management support is centered on enabling patients to develop a set of behavioral skills and abilities to help them navigate a range of disease management tasks across different chronic conditions.

In an RCT of people with knee OA, published in the New England Journal of Medicine, we found that 3 out of 4 patients eligible for total knee replacement improved enough from self-management support, supervised exercise therapy and other non-surgical treatments to postpone surgery for at least one year. Furthermore, in patients with T2DM, 56% did not take antidiabetic medication after 1 year of supervised exercise therapy, self-management support and diet. Together, these studies indicate the potential of combining exercise, self-management and other treatments to reduce the need for surgery and medication. A recent cohort study found that an eight-week exercise and self-management program demonstrated similar improvements in health outcomes for people with OA and the comorbidities included in the current study as for people without comorbidities.

Altogether, this highlights exercise therapy and self-management support as viable treatment options for people with multimorbidity, but the evidence supporting this is of low quality and more high-quality RCTs are needed to improve care for the millions of people suffering from multimorbidity worldwide.

The overall aim of the MOBILIZE project is to empower patients with multimorbidity to take a more active role in their health care through a personalized exercise therapy and self-management support program so that they may reduce symptoms of the individual conditions, increase quality of life and physical function and prevent development of other chronic conditions. To ensure relevance to the patients and the health care system and to make sure that the project is implementable in clinical practice afterwards, strong interdisciplinary collaboration involving many different scientific methodologies and a high degree of patient involvement throughout the entire research process are at the heart of the project. The MOBILIZE project has received funding from several foundations, including the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 801790). Building on the Medical Research Council's framework for the development and evaluation of complex interventions, the MOBILIZE project has four phases. During the first phase of the project, outcomes and biomarkers that predict better health outcome from different types of exercise therapy and exercise characteristics associated with a better outcome in people with different combinations of chronic conditions will be identified through exploratory observational cohort studies of people with osteoarthritis who have undergone an 8-week exercise therapy and education program in Denmark (GLA:D) as well as scoping reviews, systematic reviews and meta-analyses that summarize the existing evidence. Subsequently, in phase 2, a 12-week exercise therapy and self-management support program will be developed based on existing recommendations for exercise and strategies to facilitate behavioral changes. To ensure a high degree of patient and provider involvement, focus group interviews will be conducted with patients with multimorbidity, health care providers and other relevant stakeholders to acquire their views and perspectives on multimorbidity and exercise. Once this phase is completed, the exercise therapy and self-management support program will be tested in a feasibility trial involving 20 patients with multimorbidity (recruited from Feb 2021 and onwards). The same procedures and outcomes as in the subsequent RCT will be used, and data will be collected at baseline and after the 12-week intervention. The feasibility trial will primarily focus on feasibility outcomes (recruitment, retention, adherence to treatment, burden of outcomes, improvements in outcomes, adverse events), using a red/amber/green traffic light system, guiding the progression to the subsequent RCT. Experiences from the feasibility trial will be used to evaluate and implement any adjustments that need to be made prior to commencing the RCT (described in details in the current trial registration). The RCT corresponds to phase 3, while phase 4 focuses on developing a model for implementation of the personalized exercise therapy and self-management support program in clinical practice, if supported by the study findings.

The aim of the RCT described in this clinical trial registration is to investigate the effects of a personalized exercise therapy and self-management support program in addition to usual care on self-reported, objectively measured and physiological outcomes in people with multimorbidity (i.e. at least two of the following conditions: OA (knee or hip), heart condition (HF or CHD), hypertension, T2DM, COPD and depression). The primary endpoint is 12 months, but 4- and 6-month follow-ups are included as well and a 12-month health economic evaluation of the program will be conducted. The 4-month follow-up corresponds to immediately after the intervention, including the time it takes to conduct the baseline measurements and be enrolled in the group-based program.

The primary study hypothesis is that a personalized exercise therapy and self-management support program in addition to usual care will improve quality of life more than usual care alone when measured at 12 months with concurrent positive effects on secondary outcomes. Furthermore, it is hypothesized that the program will be cost-effective at 12 months.

People will be recruited via the recruitment centers mentioned in this registration as well as via self-referral (Facebook posts, newspaper articles and flyers).

People who only fulfil some of the eligibility criteria (aged 18 years or above, at least two of the relevant conditions and do not have psychosis disorders, post-traumatic stress disorder, Obsessive Compulsive Disorder, attention deficit hyperactivity disorder, autism, anorexia nervosa/bulimia nervosa or an abuse or other reasons for exclusion) or people fulfilling all eligibility criteria, but unwilling to participate in the RCT, will be offered participation in an observational cohort study where only the self-reported outcomes are completed. Recruitment for the cohort will start and end with the recruitment for the RCT.

Eligibility criteria: Inclusion Criteria:

* At least two of the following conditions: OA (knee or hip), COPD, heart condition (HF or CHD), hypertension, T2DM, depression (having other comorbidities does not exclude a patient)
* Adults aged 18 years or above
* Able to walk 3 meters without any assistance
* A score of 3 or above on the Bayliss' Disease Burden: Morbidity Assessment by Self- Report scale for at least one of the conditions listed above and a score of 2 or above for at least one of the other listed conditions
* Willingness and ability to participate in a 12-week supervised exercise therapy and self- management support program twice a week

Exclusion Criteria:

* Participation in supervised systematic exercise for one of their diseases within the last 3 months
* Patients with an unstable health condition or at risk of serious adverse events as evaluated by a medical specialist
* Patients categorized as Class IV on the New York Heart Association (NYHA) Functional Classification scale
* Terminal patients and patients with life expectancy of less than 12 months
* Patients with psychosis disorders, post-traumatic stress disorder, Obsessive Compulsive Disorder, attention deficit hyperactivity disorder, autism, anorexia nervosa/bulimia nervosa and patients with dependency disorders
* Other reasons (unable to understand Danish, mentally unable to participate, etc.)

Primary outcomes:
measure: EQ-5D-5L, the descriptive index
timeFrame: Primary endpoint: Change from baseline to 12 months
Secondary outcomes:
measure: 6-minute walk test
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Burden of illness measure
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: 30-second chair-stand test
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Depression Scale
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Anxiety
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Self-Efficacy
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Overall functioning and disability
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Adverse events
timeFrame: Primary endpoint: 12 months
measure: Steps per day
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Minutes/day spent being physically active with at least light intensity
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: EQ-5D-5L, the subscale EQ VAS
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Mortality
timeFrame: Primary endpoint: 12 months
Other outcomes:
measure: Isometric knee-extension strength
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Balance
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Pain (yes/no) in left and right knee and hip + worst joint if more than one
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Stress
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Systolic and diastolic blood pressure
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Concentration of cholesterol (HDL and LDL) and triglyceride
timeFrame: Primary endpoint: Change from baseline to 4 months
measure: Concentration of Fasting glucose
timeFrame: Primary endpoint: Change from baseline to 4 months
measure: Concentration of Fasting insulin
timeFrame: Primary endpoint: Change from baseline to 4 months
measure: Concentration of HbA1c
timeFrame: Primary endpoint: Change from baseline to 4 months
measure: Concentration of high-sensitivity C-reactive protein (hs-CRP)
timeFrame: Primary endpoint: Change from baseline to 4 months
measure: Concentration of Tumor necrosis factor (TNF)
timeFrame: Primary endpoint: Change from baseline to 4 months
measure: Concentration of Interleukin 6 (IL-6)
timeFrame: Primary endpoint: Change from baseline to 4 months
measure: Concentration of Interleukin-1 receptor antagonist (IL-1ra)
timeFrame: Primary endpoint: Change from baseline to 4 months
measure: Weight
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Adapted Fried Frailty and pre-frailty criteria
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Fatigue
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Disease-specific treatment
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Knee/hip pain, VAS
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Patient Acceptable Symptom State (PASS)
timeFrame: Primary endpoint: 12 months
measure: Patient-reported treatment failure
timeFrame: Primary endpoint: 12 months.
measure: Adherence
timeFrame: Primary endpoint: 4 months
measure: Other treatment during follow-up
timeFrame: Primary endpoint: 12 months
measure: Work status
timeFrame: 12 months.
measure: Smoking
timeFrame: Primary endpoint: 12 months
measure: Questionnaire burden (only feasibility study)
timeFrame: Primary endpoint: 4 months
measure: Assessment burden (only feasibility study)
timeFrame: Primary endpoint: 4 months
measure: Isometric handgrip strength
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Multimorbidity Treatment Burden
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Short form of Patient Activation Measure (PAM)
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Bodily pain
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Sedentary behaviour
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Individual items from the 12-item WHODAS 2.0
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Spirometry (FEV1)
timeFrame: Only assessed at baseline.
measure: Self-reported physical activity level
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Global Perceived Effect (GPE)
timeFrame: Primary endpoint: 12 months
measure: Falls
timeFrame: Primary endpoint: 12 months
measure: Fear of falling
timeFrame: Primary endpoint: 12 months
measure: Sedentary activity: Time spent on sedentary activities
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Light physical activity: Time spent on light intensity activities
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Moderate physical activity: Time spent on moderate intensity activities
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Vigorous physical activity: Time spent on vigorous intensity activities
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Moderate to vigorous physical activity: Time spent on moderate to vigorous intensity activities
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Adherence to the World Health Organization (WHO) physical activity recommendations, i.e. ≥150 min. MVPA or ≥75 min. VPA weekly activities
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Sleep, objectively measured
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Sleep quantity, self-reported
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Modified Karolinska Sleep Questionnaire
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Vigorous Intermittent Lifestyle Physical Activity (VILPA).
timeFrame: Primary endpoint: Change from baseline to 12 months
measure: Moderate-to-Vigorous Intermittent Lifestyle Physical Activity (MV-ILPA).
timeFrame: Primary endpoint: Change from baseline to 12 months
Locations:
city: Holbæk
country: Denmark
facility: Holbæk Sygehus
city: Holbæk
country: Denmark
facility: Læge Poul Erik Holst
city: Kirke Hvalsø
country: Denmark
facility: Lægehuset Tolskovvej
city: Køge
country: Denmark
facility: Department of Orthopedics, Zealand University Hospital
city: Nakskov
country: Denmark
facility: Community Clinic
city: Næstved
country: Denmark
facility: Department of Orthopaedic Surgery, Næstved Hospital
city: Næstved
country: Denmark
facility: Department of Pulmonology, Næstved Hospital
city: Næstved
country: Denmark
facility: Lægehuset Ostenfeldt
city: Næstved
country: Denmark
facility: Psychiatric Clinic Næstved
city: Roskilde
country: Denmark
facility: Community Psychiatry Roskilde
city: Roskilde
country: Denmark
facility: Department of Cardiology, Zealand University Hospital
city: Roskilde
country: Denmark
facility: Lægerne Algade 17
city: Slagelse
country: Denmark
facility: Department of Cardiology and Endocrinology, Slagelse Hospital
city: Slagelse
country: Denmark
facility: Lægerne Reventlow og Wolfhagen
city: Slagelse
country: Denmark
facility: Psychiatric Hospital West, Slagelse
city: Slagelse
country: Denmark
facility: Nykøbing Falster County Hospital
Study officials:
affiliation: Næstved, Slagelse and Ringsted hospital and University of Southern Denmark
name: Søren T Skou, PT, MSc, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Pulmonology, Næstved Hospital
name: Uffe Bødtger, MD
role: STUDY_CHAIR
affiliation: Department of Cardiology and Endocrinology, Slagelse Hospital
name: Peter Gæde, MD
role: STUDY_CHAIR
affiliation: Department of Orthopaedic Surgery, Næstved Hospital
name: Manuel J Bieder, MD
role: STUDY_CHAIR
affiliation: Psychiatric Hospital West, Slagelse
name: Sidse Arnfred, MD
role: STUDY_CHAIR
affiliation: Municipality of Roskilde
name: Christine Bodilsen, PT, MSc, PhD
role: STUDY_CHAIR
affiliation: Municipality of Lolland
name: Jan A Overgaard, PT, MSc
role: STUDY_CHAIR
affiliation: Næstved, Slagelse and Ringsted hospital and University of Southern Denmark
name: Alessio Bricca, MSc, PhD
role: STUDY_CHAIR
affiliation: Næstved, Slagelse and Ringsted hospital and University of Southern Denmark
name: Madalina Jäger, MSc, PhD
role: STUDY_CHAIR
affiliation: Nykøbing Falster County Hospital
name: Christian S Christiansen, MD
role: STUDY_CHAIR
affiliation: Holbaek Sygehus
name: Anne Merete B Soja, MD, PhD, DMSc
role: STUDY_CHAIR
affiliation: Department of Cardiology, Zealand University Hospital, Roskilde
name: Niels Eske Bruun, MD
role: STUDY_CHAIR
affiliation: Lægerne Reventlow og Wolfhagen, Slagelse
name: Johan L Reventlow, MD
role: STUDY_CHAIR
affiliation: Lægerne Algade 17, Roskilde
name: Andreas Heltberg, MD, PhD
role: STUDY_CHAIR
affiliation: University of Southern Denmark
name: Lau C Thygesen, MSc, PhD
role: STUDY_CHAIR
affiliation: Læge Poul Erik Holst, Holbæk
name: Poul Erik Holst, MD
role: STUDY_CHAIR
affiliation: Psychiatric Clinic Næstved
name: Rita M Andersen, MSc
role: STUDY_CHAIR
affiliation: Department of Orthopedics, Zealand University Hospital, Køge
name: Amir Pasha Attarzadeh, MD
role: STUDY_CHAIR
affiliation: Community Psychiatry Roskilde
name: Mickey T Kongerslev, MSc
role: STUDY_CHAIR
affiliation: Lægehuset Tolskovvej, Hvalsø
name: Louise Richelieu, MD
role: STUDY_CHAIR
affiliation: Lægehuset Ostenfeldt, Næstved
name: Signe Aspelin, MD
role: STUDY_CHAIR
affiliation: Lægehuset Ostenfeldt, Næstved
name: Sille Capion, MD
role: STUDY_CHAIR
affiliation: Community Clinic Nakskov
name: Rune F Nielsen, Nurse
role: STUDY_CHAIR
References: