Clinical trial NCT06715852: Moving on! A Tailored Treatment in a Primary Care Setting for Individuals With Anxiety Disorders?
Official title: Moving on! Can a Tailored Treatment in a Primary Care Setting Reduce Symptoms, Healthcare Consumption, Sick Leave and Prevent Pain and Hypertension in Individuals With Anxiety Disorders?
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Anxiety
Lead sponsor: Vastra Gotaland Region
Sponsor class: OTHER_GOV
Collaborators: name: Göteborg University
First posted: 2024-12-04
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A clinical intervention with a matched design and parallel arms.
Primary purpose: TREATMENT

Brief summary: The goal of this clinical study is to investigate the effects of two different interventions in patients with anxiety disorder and who seeks help at primary care centers. The participants will choose between two interventions:

1. A 12-week physical exercise program with three training sessions per week, or
2. A modified version of eHealth Lift, a digital development of the Health Lift, an evidence based lifestyle-intervention for health promotion and prevention in primary health care.

The participant will fill in self-assessment scales and questionnaires and also have BMI and blood pressure measured at the start of the study, at 12-weeks after the study start and after 1 year.

The main question the investigators aim to answer is if the interventions are better than treatment as usual for this group of patients regarding:

* symptoms of anxiety and depression
* pain
* sleep
* alcohol habits
* fatigue
* general health
* work ability/sick leave
* physical activity
* perceived quality of life
* BMI and blood pressure
* number of health care contacts
* psychopharmaceuticals and analgesics prescribed
* health literacy

Detailed description: Every third patient in the waiting room at a Swedish primary healthcare center is seeking help for common mental disorders including anxiety (1). Anxiety disorders substantially reduce quality of life and daily functioning and are, among mental disorders, the second leading cause of years lived with disability and the sixth-leading cause of disability globally. Anxiety disorders are also associated with elevated risks of pain, cardiovascular disease (CVD) and premature mortality (2), emphasizing the importance of finding effective treatment strategies that can be addressed in primary care.

Specific research questions:

* Can a tailored treatment and secondary prevention in a primary care setting reduce symptoms of anxiety, healthcare consumption, sick leave, pain and prevent hypertension in individuals with anxiety disorders?
* Are there long-term effects at 1 year of follow-up regarding the outcome measures?
* Is the treatment/secondary preventive strategy associated with health economic benefits?

Significance and scientific novelty: Despite the high burden of anxiety, there are major knowledge gaps when it comes to secondary preventive measures. This intervention aims to reduce anxiety, improve the quality of life, work ability and health in primary health care patients with anxiety disorders. Little research has focused on lifestyle improvements or exercise specifically in the treatment of anxiety. In Sweden there are guidelines from The National Board of Health and welfare for treatment of depression with exercise, but guidelines for treatment of anxiety disorders are currently lacking. Also results from this study may extend the current understanding and practice in the field of treatment and secondary prevention of anxiety disorders within primary care.

This project aims to combine evidence-based interventions to tailor a lifestyle intervention with different steps focusing on patient control and participation since the individual chooses the intervention arm. Two evidence-based lifestyle interventions will combined and evaluated: the modified eHealth Lift/Care manager according to regional clinical guidelines and PHYSBI, a promising new strategy with an intensive training program, a new approach for treating anxiety disorders. If a simple intervention program in primary care can alleviate anxiety, improve quality of life, cognitive performance, and work ability, prevent pain and hypertension, this may have a great positive impact both at the individual level and from a societal perspective. The investigators hope to increase the availability of person-centered, evidence-based and cost-effective measures to promote both physical and mental health in patients with anxiety disorders. Moreover, the interventions are designed to easily be implemented in regular primary care activities.

Design of study: A clinical intervention with a matched design with two parallel arms and three assessment points (baseline, post-intervention and 1 year of follow-up).

Setting: Primary care centers in Region Västra Götaland (VGR), Sweden Participants: Patients aged 18-65 diagnosed with anxiety disorders attending 20 primary care centers (PCCs) within the VGR. Participants will be recruited by personnel at the PCCs (doctors, psychologists, nurses), through information material at the PCCs (posters, flyers and handouts) and by using the primary care system Medrave to identify and contact suitable patients. Eligibility criteria can be found elsewhere in the ClinicalTrials.gov protocol. Participants will sign a written informed consent and informed about the possibility to withdraw from the study at any time without disadvantages.

Matching: PCCs connected to a rehabilitation clinic will be assigned as intervention PCCs. Thsese PCCs will be matched for the following variables 1) size of the PCC, 2) socioeconomy as Care Need Index (CNI) and 3). Matching will be executed in order to identify suitable PCCs with care as usual (controls).

The intervention: The 10 PCCs allocated to intervention will offer all patients with a registered anxiety diagnosis in the PCCs electronic patient register as well as patients newly diagnosed with any of the above listed disorders to participate in an intervention program. The patient chooses the intervention arm, and the focus is on person-centredness, control, empowerment and participation.

The two intervention-options are:

1. Modified eHealth Lift, a digital development of the Health Lift, an evidence based lifestyle-intervention for health promotion and prevention in primary health care. This intervention will be executed together with care manager contact according to regional clinical guidelines.
2. The moderate-high intensity arm of PHYSBI, an individualized 12-week training program for anxiety disorders including 3 occasions/week. The moderate intensity arm of PHYSBI, which also will contain elements of high intensity, corresponds to 3.0-8.9 metabolic equivalents, Borg Rating of Perceived Exertion 12-17 and 60-94% of maximal heart rate. The intervention includes cardiorespiratory and resistance training in a group-session (3). The study physiotherapists design individualized exercise programs during a single one-to-one session with the patients.

CAU (PCCs allocated to non-intervention): At Swedish PCCs, care as usual (CAU) for patients with anxiety disorders can consist of visits to various healthcare professionals (such as physicians, nurses, psychologists, therapists, physiotherapists). The treatment should follow the regional guidelines, which are based on the national evidence-based clinical guidelines for anxiety disorders (National guidelines for care of depression and anxiety disorders, The Swedish National Board of Health and Welfare, Stockholm 2020). These guidelines include psychopedagogic support, psychotherapy (cognitive behavioural therapy (CBT) face-to-face or internet-mediated), psychopharmaceutical treatment and/or sick listing (preferably partial).

Outcome measures: Individual data on symptoms of anxiety, depression, general health, pain, sleep, fatigue, work ability, physical activity and perceived quality of life will be obtained through established self-assessment scales and collected for each intervention arm. Patients will self-report smoking, concurrent illnesses, pain, usage of prescribed drugs and physical activity using a questionnaire designed by the research team. Data will also be obtained from the healthcare database VEGA (Database for health-care consumption in VGR), the national Patient register, the regional prescribed drug register Digitalis, the national Prescribed drug register and the MiDAS database at Försäkringskassan (includes data on sick leave \>14 days). Specification of outcomes can be found elsewhere in the ClinicalTrials.gov protocol.

Timeline and Workplan: During 2024 a Clinical Trial registration will be submitted. The investigators already have established contacts with gyms, the PHCRs and the Research and Development primary healthcare centres. During 2024 the collaborations with the primary healthcare organization, the PHCRs and health centres will be further established. A steering committee will be formed and the study procedures tested. During autumn 2024 the PCCs will be invited to participate. At the intervention PCCs, the recruitment of patients will be facilitated through a research nurse. At every PCC, a unique care manager manager which has been implemented at all PCCs in VGR since 2016 (4) handles the modified eHealth Lift, and the physiotherapists implement PHYSBI. The PHCRs will perform the PHYSBI arm and the involved PCCs will implement the modified eHealth Lift arm continuously during the intervention year of 2025. Study start date is anticipated to be in Jan 2025 and primary completion date in Dec 2026 (1 year of follow-up). Outcome data will be collected throughout the period 2025-2026. In 2026-2027 data will be processed, analyzed and scientific papers produced.

Data analysis and statistics: The majority of outcome variables are scale variables that may be treated as continuous variables and therefore primarily modelled using linear regression. These are scales for symptoms of anxiety, depression, pain, sleep, general health, perceived quality of life, sick leave days, number of health care contacts and number and types of psychopharmaceuticals prescribed. Data will be presented using descriptive statistics, including means and standard deviations for continuous variables, and frequencies and percentages for categorical variables Group differences by intervention status (modified eHealth Lift, PHYSBI, or CAU) will be assessed by Kruskal-Wallis test and chi-square tests, respectively. The average change in continuous outcomes will be analyzed using linear regression, with intervention as categorical predictor and baseline levels as covariates.

In the case of count data the investigators will test whether Poisson or negative binomial models are more appropriate than linear regression. The correlation of outcomes between patients from the same PCC will be modelled using a hierarchical linear model including PCC as random effect. A more detailed analysis of the longitudinal change will be based on repeated-measure models that also account for the correlations within individuals. Interaction terms for PCC status and time will test whether time trends differ by intervention status. Binary endpoints such as sick leave will be analyzed using logistic regression with adjustment for correlations as described for the linear models. All regression models will be adjusted for age, sex, as well as for variables on PCC-level such as socioeconomy, number of patients listed per PCC (size), and proportion of patients with anxiety diagnoses.

Power considerations: A power calculations has been performed based on 20 health centres distributed 50:50 i.e. 10 controls and 10 with two interventions. However, as patients are allowed to choose between the two intervention types (modified eHealth Lift or PHYSBI) the investigators will consider an unequal distribution of intervention types, e.g. 70:30 % for the modified eHealth Lift and PHYSBI. As the main outcome measures are continuous, Cohen's d = mean difference/standard deviation is considered as outcome measure, assuming small to medium effect size, i.e. d = 0.2 - 0.5 \[51\]. Power analysis was performed using a STATA procedure for one-way ANOVA. For a change (baseline to 3 months) effects sizes with d ≥ 0.2 and a power of ≥0.9 (significance level = 0.05) can be observed with a total of 320 individuals, distributed as 160 patients without intervention, 112 with the modified eHealth Lift, and 48 with PHYSBI. The same sample size will yield even larger statistical power if the group size for the modified eHealth Lift and PHYSBI were more alike.

Health-economic analyses: Cost-effectiveness analyses will be performed separately, comparing the two intervention arms to no CAU, including both direct (healthcare and pharmaceutical utilization) and indirect (long-term sickness and absenteeism from work) costs. Cost-effectiveness analyses will be based on the primary data collected within the project and based on a combination of primary data and secondary data from other sources for lifetime time perspectives. The long-term analyses will be performed using a health-economic simulation model projecting the outcomes and cost-effectiveness at the 1-year follow-up to a longer time period (5 years and lifelong).

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of anxiety disorder (panic syndrome, 41.0; generalized anxiety, F41.1; mixed anxiety- and depression, F41.2 and F41.3; anxiety not otherwise specified, F41.9).
* Seeking care at primary care centers within the Region Västra Götaland.
* With or without ongoing treatment with psychoactive medication (antidepressants or anxiolytics).

Exclusion Criteria:

* Pregnancy
* Physical difficulties in performing a physical exercise program
* Pathological electrocardiogram
* Low BMI (under 17.5)
* Ongoing alcohol/substance abuse
* Ongoing exhaustion disorder or psychotic disorder
* Newly discovered (within 6 months) atrial fibrillation
* High suicide risk as assessed by the general practitioner
* Limited knowledge in the Swedish language.

Primary outcomes:
measure: Symptoms of anxiety - BAI
timeFrame: At study start
measure: Symptoms of anxiety - BAI
timeFrame: After 12-weeks intervention
measure: Symptoms of anxiety - BAI
timeFrame: After one year follow-up
measure: Symptoms of Generalized Anxiety Disorder - GAD-7
timeFrame: At study start
measure: Symptoms of Generalized Anxiety Disorder - GAD-7
timeFrame: After 12-weeks intervention
measure: Symptoms of Generalized Anxiety Disorder - GAD-7
timeFrame: After one year follow-up
measure: Symptoms of anxiety - HAD
timeFrame: At study start
measure: Symptoms of anxiety - HAD
timeFrame: After 12-weeks intervention
measure: Symptoms of anxiety - HAD
timeFrame: After one year follow-up
measure: Symptoms of inner tension - MADRS-S; question 2
timeFrame: At study start
measure: Symptoms of inner tension - MADRS-S; question 2
timeFrame: After 12-weeks intervention
measure: Symptoms of inner tension - MADRS-S; question 2
timeFrame: After one year follow-up
Secondary outcomes:
measure: Symptoms of depression - MADRS-S
timeFrame: At study start
measure: Symptoms of depression - MADRS-S
timeFrame: After 12-weeks intervention
measure: Symptoms of depression - MADRS-S
timeFrame: After one year follow-up
measure: Symptoms of pain - PSQ
timeFrame: At study start
measure: Symptoms of pain - PSQ
timeFrame: After 12-weeks intervention
measure: Symptoms of pain - PSQ
timeFrame: After one year follow-up
measure: Sleep quality - ISI
timeFrame: At study start
measure: Sleep quality - ISI
timeFrame: After 12-weeks intervention
measure: Sleep quality - ISI
timeFrame: After one year follow-up
measure: Alcohol habits - AUDIT
timeFrame: At study start
measure: Alcohol habits - AUDIT
timeFrame: After 12-weeks intervention
measure: Alcohol habits - AUDIT
timeFrame: After one year follow-up
measure: Fatigue - MFS
timeFrame: At study start
measure: Fatigue - MFS
timeFrame: After 12-weeks intervention
measure: Fatigue - MFS
timeFrame: After one year follow-up
measure: Health-related quality of life - EQ-5D
timeFrame: At study start
measure: Health-related quality of life - EQ-5D
timeFrame: After 12-weeks intervention
measure: Health-related quality of life - EQ-5D
timeFrame: After one year follow-up
measure: Work ability - C2WI
timeFrame: At study start
measure: Work ability - C2WI
timeFrame: After 12-weeks intervention
measure: Work ability - C2WI
timeFrame: After one year follow-up
measure: Physical activity - IPAQ
timeFrame: At study start
measure: Physical activity - IPAQ
timeFrame: After 12-weeks intervention
measure: Physical activity - IPAQ
timeFrame: After one year follow-up
measure: Body mass index - BMI
timeFrame: At study start
measure: Body mass index - BMI
timeFrame: After 12-weeks intervention
measure: Body mass index - BMI
timeFrame: After one year follow-up
measure: Blood pressure - mmHg
timeFrame: At study start
measure: Blood pressure - mmHg
timeFrame: After 12-weeks intervention
measure: Blood pressure - mmHg
timeFrame: After one year follow-up
measure: Health care contacts - registry data
timeFrame: At study start
measure: Health care contacts - registry data
timeFrame: After 12-weeks intervention
measure: Health care contacts - registry data
timeFrame: After one year follow-up
measure: Prescribed medication - registry data
timeFrame: At study start
measure: Prescribed medication - registry data
timeFrame: After 12-weeks intervention
measure: Prescribed medication - registry data
timeFrame: After one year follow-up
measure: Sick leave - registry data
timeFrame: At study start
measure: Sick leave - registry data
timeFrame: After 12-weeks intervention
measure: Sick leave - registry data
timeFrame: After one year follow-up
measure: Mental and Physical health - registry data
timeFrame: At study start
measure: Mental and Physical health - registry data
timeFrame: After 12-weeks intervention
measure: Mental and Physical health - registry data
timeFrame: After one year follow-up
measure: Sick leave and work ability - questionnaire
timeFrame: At study start
measure: Sick leave and work ability - questionnaire
timeFrame: After 12-weeks intervention
measure: Sick leave and work ability - questionnaire
timeFrame: After one year follow-up
measure: Used psychopharmaceuticals - questionnaire
timeFrame: At study start
measure: Used psychopharmaceuticals - questionnaire
timeFrame: After 12-weeks intervention
measure: Used psychopharmaceuticals - questionnaire
timeFrame: After one year follow-up
measure: Physical activity - questionnaire
timeFrame: At study start
measure: Physical activity - questionnaire
timeFrame: After 12-weeks intervention
measure: Physical activity - questionnaire
timeFrame: After one year follow-up
measure: Pain - questionnaire
timeFrame: At study start
measure: Pain - questionnaire
timeFrame: After 12-weeks intervention
measure: Pain - questionnaire
timeFrame: After one year follow-up
measure: Health care consumption - questionnaire
timeFrame: At study start
measure: Health care consumption - questionnaire
timeFrame: After 12-weeks intervention
measure: Health care consumption - questionnaire
timeFrame: After one year follow-up
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg
Study officials:
affiliation: School of Public Health and Community Medicine, University of Gothenburg
name: Maria Åberg, PhD, MD
role: PRINCIPAL_INVESTIGATOR
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