Personalized Exercise Therapy and Self-management Support for Patients With Multimorbidity

NCT ID: NCT04645732

Last Updated: 2024-08-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 228 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-01
• Study Completion Date: 2024-07-31

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.

Conditions

Osteoarthritis, Knee; Osteoarthritis, Hip; Heart Failure; Coronary Heart Disease; Hypertension; Type2 Diabetes; Chronic Obstructive Pulmonary Disease; Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Personalized exercise therapy and self-management program in addition to usual care

Participants randomized to the personalized exercise therapy and self-management support program will participate in a 12-week program tailored to people with multimorbidity at one of the intervention sites. The program will consist of 24 exercise therapy and self-management sessions distributed across the program (twice weekly, each lasting around 1.5 hour).

Furthermore, this group will receive the treatment described under usual care below.

Group Type: EXPERIMENTAL

Personalized exercise therapy and self-management support program

Intervention Type: BEHAVIORAL

See description under Arms

Usual care

Intervention Type: OTHER

See description under Arms

Usual care alone

Usual care is the care that the participants would receive had they not participated in the study, i.e. treatments or services that are routinely provided in the settings from which the participants are recruited. Participants will continue their current treatment, if needed, and be allowed to receive other treatments if their general practitioner or specialist finds it relevant for their particular comorbidities.

Group Type: ACTIVE_COMPARATOR

Usual care

Intervention Type: OTHER

See description under Arms

Interventions

Personalized exercise therapy and self-management support program

See description under Arms

Intervention Type: BEHAVIORAL

Usual care

See description under Arms

Intervention Type: OTHER

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.)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Naestved Hospital

OTHER

Sponsor Role: collaborator

Slagelse Hospital

OTHER

Sponsor Role: collaborator

Lolland Municipality

UNKNOWN

Sponsor Role: collaborator

Roskilde Municipality

UNKNOWN

Sponsor Role: collaborator

Psychiatric Hospital West, Slagelse

UNKNOWN

Sponsor Role: collaborator

Næstved, Slagelse and Ringsted Hospitals' Research Fund

UNKNOWN

Sponsor Role: collaborator

Association of Danish Physiotherapists

OTHER

Sponsor Role: collaborator

The Danish Health Confederation through the Development and Research Fund

UNKNOWN

Sponsor Role: collaborator

European Research Council

OTHER

Sponsor Role: collaborator

Holbaek Sygehus

OTHER

Sponsor Role: collaborator

Nykøbing Falster County Hospital

OTHER

Sponsor Role: collaborator

FysioDanmark Holbæk

UNKNOWN

Sponsor Role: collaborator

Zealand University Hospital

OTHER

Sponsor Role: collaborator

Lægerne Reventlow og Wolfhagen, Slagelse

UNKNOWN

Sponsor Role: collaborator

Lægerne Algade 17, Roskilde

UNKNOWN

Sponsor Role: collaborator

University of Southern Denmark

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Søren T Skou, PT, MSc, PhD

Role: PRINCIPAL_INVESTIGATOR

Næstved, Slagelse and Ringsted hospital and University of Southern Denmark

Uffe Bødtger, MD

Role: STUDY_CHAIR

Department of Pulmonology, Næstved Hospital

Peter Gæde, MD

Role: STUDY_CHAIR

Department of Cardiology and Endocrinology, Slagelse Hospital

Manuel J Bieder, MD

Role: STUDY_CHAIR

Department of Orthopaedic Surgery, Næstved Hospital

Sidse Arnfred, MD

Role: STUDY_CHAIR

Psychiatric Hospital West, Slagelse

Christine Bodilsen, PT, MSc, PhD

Role: STUDY_CHAIR

Municipality of Roskilde

Jan A Overgaard, PT, MSc

Role: STUDY_CHAIR

Municipality of Lolland

Alessio Bricca, MSc, PhD

Role: STUDY_CHAIR

Næstved, Slagelse and Ringsted hospital and University of Southern Denmark

Madalina Jäger, MSc, PhD

Role: STUDY_CHAIR

Næstved, Slagelse and Ringsted hospital and University of Southern Denmark

Christian S Christiansen, MD

Role: STUDY_CHAIR

Nykøbing Falster County Hospital

Anne Merete B Soja, MD, PhD, DMSc

Role: STUDY_CHAIR

Holbaek Sygehus

Niels Eske Bruun, MD

Role: STUDY_CHAIR

Department of Cardiology, Zealand University Hospital, Roskilde

Johan L Reventlow, MD

Role: STUDY_CHAIR

Lægerne Reventlow og Wolfhagen, Slagelse

Andreas Heltberg, MD, PhD

Role: STUDY_CHAIR

Lægerne Algade 17, Roskilde

Lau C Thygesen, MSc, PhD

Role: STUDY_CHAIR

University of Southern Denmark

Poul Erik Holst, MD

Role: STUDY_CHAIR

Læge Poul Erik Holst, Holbæk

Rita M Andersen, MSc

Role: STUDY_CHAIR

Psychiatric Clinic Næstved

Amir Pasha Attarzadeh, MD

Role: STUDY_CHAIR

Department of Orthopedics, Zealand University Hospital, Køge

Mickey T Kongerslev, MSc

Role: STUDY_CHAIR

Community Psychiatry Roskilde

Louise Richelieu, MD

Role: STUDY_CHAIR

Lægehuset Tolskovvej, Hvalsø

Signe Aspelin, MD

Role: STUDY_CHAIR

Lægehuset Ostenfeldt, Næstved

Sille Capion, MD

Role: STUDY_CHAIR

Lægehuset Ostenfeldt, Næstved

Rune F Nielsen, Nurse

Role: STUDY_CHAIR

Community Clinic Nakskov

Locations

Holbæk Sygehus

Holbæk, , Denmark

Læge Poul Erik Holst

Holbæk, , Denmark

Lægehuset Tolskovvej

Kirke Hvalsø, , Denmark

Department of Orthopedics, Zealand University Hospital

Køge, , Denmark

Community Clinic

Nakskov, , Denmark

Department of Orthopaedic Surgery, Næstved Hospital

Næstved, , Denmark

Department of Pulmonology, Næstved Hospital

Næstved, , Denmark

Lægehuset Ostenfeldt

Næstved, , Denmark

Psychiatric Clinic Næstved

Næstved, , Denmark

Community Psychiatry Roskilde

Roskilde, , Denmark

Department of Cardiology, Zealand University Hospital

Roskilde, , Denmark

Lægerne Algade 17

Roskilde, , Denmark

Department of Cardiology and Endocrinology, Slagelse Hospital

Slagelse, , Denmark

Lægerne Reventlow og Wolfhagen

Slagelse, , Denmark

Psychiatric Hospital West, Slagelse

Slagelse, , Denmark

Nykøbing Falster County Hospital

Slagelse, , Denmark

Countries

Denmark

References

Skou ST, Nyberg M, Dideriksen M, Rasmussen H, Overgaard JA, Bodilsen C, Soja AMB, Attarzadeh AP, Bieder MJ, Dridi NP, Heltberg A, Gaede PH, Reventlow JL, Arnfred S, Bodtger U, Brond JC, Thygesen LC, Moller SP, Jager M, Bricca A. Exercise therapy and self-management support for individuals with multimorbidity: a randomized and controlled trial. Nat Med. 2025 Sep;31(9):3176-3182. doi: 10.1038/s41591-025-03779-4. Epub 2025 Jun 30.

Reference Type: DERIVED

PMID: 40588675 (View on PubMed)

Skou ST, Brodsgaard RH, Nyberg M, Dideriksen M, Bodtger U, Bricca A, Jager M. Personalised exercise therapy and self-management support for people with multimorbidity: feasibility of the MOBILIZE intervention. Pilot Feasibility Stud. 2023 Jan 18;9(1):12. doi: 10.1186/s40814-023-01242-0.

Reference Type: DERIVED

PMID: 36653858 (View on PubMed)

Related Links

https://osf.io/qk6yg/

Open Science Framework platform for MOBILIZE

https://www.mobilize-project.dk/?lang=en

MOBILIZE webpage

Other Identifiers

801790

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

SJ-857

Identifier Type: -

Identifier Source: org_study_id