Clinical trial NCT05877534: Effects of Individual Tailored Physical Exercise in Patients With POTS After COVID-19 - a Randomized Controlled Study
Official title: Effects of Individual Tailored Physical Exercise in Patients With Post COVID-19 Condition, Diagnosed With Postural Orthostatic Tachycardia Syndrome (POTS) - a Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Postural Orthostatic Tachycardia Syndrome
COVID-19
Post COVID-19 Condition
Post-Acute COVID-19 Syndrome
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Karolinska University Hospital
First posted: 2023-05-26
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Covid-19 has the potential to affect physical, cognitive and psychological functions in multiple ways. It has been clear that a significant proportion of patients with Covid-19 develop long-term symptoms. The term post COVID-19 condition (defined by WHO) is used to describe the wide range of prolonged symptoms following the infection. Patients may need specialized rehabilitation to be able to meet the complex symptoms and problems that may arise. A more specific syndrome that seems to occur more frequently than expected in the group of non-hospitalized patients with post COVID-19 condition is the postural orthostatic tachycardia syndrome (POTS).

A randomized controlled design will be used to evaluate the effects of individual tailored physical exercise in patients with POTS after Covid-19.

Participants: Adults (\>18 years) with post COVID-19 condition and diagnosed with POTS (n=60) will be included. Exclusion criteria: known pregnancy, cancer, already ongoing individual physical exercise (specific for POTS), or not able to perform measurements and/or intervention.

Procedure and outcomes: The primary outcomes are objectively measured time in upright position and health-related quality of life. Secondary outcomes are: physical activity, physical capacity, work ability and disease specific symptoms measured with tests and questionnaires.

Prior to randomization baseline measurements will be performed, aswell as after 16 weeks, 6 months and 12 months.

Intervention: Participants randomized to intervention will receive standard care and undergo a individually designed physical exercise program during 16 weeks, supervised and guided by a physiotherapist. The intervention will consist of different exercises to enhance muscle strength and endurance. Progression will be according to a program (based on previous feasibility studie) but should be halted if post exertional malaise (PEM) or other problems occur.

Controls: Participants randomized to control will receive standard care during 16 weeks.

Measurements of both groups (control and intervention) will be repeated after completion of a period of 16 weeks.

Detailed description: Introduction:

Covid-19, was in March 2020, declared a global pandemic by the World Health Organization (WHO). In August 2021, in Sweden, over 1 100 000 cases were confirmed and over 14 000 deaths. Initially, it was suspected that Covid-19 would primarily affect the airways, but several studies have now shown that it is a disease with multisystem manifestations. The impact of the virus ranges from an asymptomatic infection to a severe and life-threatening disease that can affect the cardiac, renal gastrointestinal, nervous, endocrine, and musculoskeletal systems. Therefore, Covid-19 has the potential to affect physical, cognitive, and psychological functions in multiple ways.

It has been clear that a significant proportion of patients with Covid-19 develop long-term symptoms. Signs and symptoms may arise from any system in the body, often with significant overlap, and may develop over time. The term post COVID-19 condition (defined by WHO) is now used to describe the wide range of prolonged symptoms following the infection. Fatigue, decreased physical and psychological function have been reported in the initial recovery phase, but still little is known on the long-term consequences. Previous studies on the recovery and rehabilitation after other coronavirus shows the importance to develop tailored interventions.

A more specific syndrome that seems to occur more frequently in non-hospitalized persons with post COVID-19 condition is the postural orthostatic tachycardia syndrome (POTS). It is a chronic orthostatic intolerance where upright posture is associated with an excessive increase in heart rate (HR) and associated symptoms, such as palpitation, exercise intolerance, hypermobile joints, migraine headaches, brain-fog, sleep disturbances, and fatigue. Symptoms can be exacerbated by simple activities of daily life and the patients often report a low quality of life, equivalent to what patients with severe heart failure or COPD report. Consequently, patients seem to reduce their physical activity, which make them deconditioned and limits the activities in daily living even more.

Nevertheless, supervised individual tailored physical exercises, is a recommended non-pharmacological treatment of POTS. However, few studies have investigated the effect of physical exercise in POTS, and studies of POTS and post COVID-19 condition are very sparse. Therefore a feasibility study were performed and data found that the intervention (individually tailored physical exercise) was feasible in terms of safety, recruitment and compliance. Moreover the feasibility study provided optimistic results of the effects according to the participants physical, psychological functions as to their quality of life.

The planned RCT is part of research project (ReCOV), integrated with the clinical follow-up at Karolinska University Hospital and linked research project of patients who have been hospitalized or refereed to the clinic from primary care. The hypothesis is that an individually tailored rehabilitation program will have a beneficial effect on the ability to spend time in an upright position, as well as on HRQoL, for individuals with POTS, post COVID-19 condition.

The overall aim of this study is to evaluate the effects of an individually tailored exercise and its impact on time spent in upright position and health-related quality of life (HRQoL), physical activity, physical and psychological function and work-ability in persons with POTS, post COVID-19 condition.

Methods

Participants:

A total of 60 adult patients (\>18 years) with POTS (diagnosed by a cardiologist), post COVID-19 condition. Recruitment will take place at the outpatient clinic at Karolinska University Hospital or in the primary care in Region Stockholm. Exclusion criteria: known pregnancy, cancer, already ongoing individual physical exercise (specific for POTS) or not able to perform measurements and/or intervention.

Procedure:

Prior to randomization baseline measurements will be performed. The measurements include Active Standing (AST), Test, 6-minute Walk Test (6MWT), muscle strength with MicroFET, measurements of pulsoximetry, pulse and blood pressure before, during and after tests, and participant will report their symptoms with BORG CR10 and BORG RPE. To evaluate time in upright position participants will wear two accelerometers (ActivPAL) during a week before intervention start. Questionnaires that will be used are EQ-5D-5L, Vanderbuildt Orthostatic Symptom Scale (VOSS), Malmö POTS Symptom Scale (MaPS), Fatigue Severeity Scale (FSS), Mental Fatigue Scale (MFS), DePaul Symtom Questionnaire - Post-Exertion Malaise (DSQ-PEM), Generalized Anxiety Disorder 7-item scale (GAD-7), Patient Health Questionnaire (PHQ-9) and Insomnia Severeity Index (ISS).

Controls: Participants randomized to control will receive standard care during 16 weeks. Standard care includes (but not restricted to) information about POTS and lifestyle changes that may effect the symptoms, advice about what fluid intake and nutrition, compression garments, pharmacological interventions etc.

Intervention: Participants randomized to intervention will receive standard care (same as controls) and undergo an individually tailored physical exercise program during a period of 16 weeks. The intervention will consist of exercises to enhance muscle strength and endurance. The program includes progression regarding duration and position for the exercise (starting i laying position and progression towards upright position). Progression should be halted if post exertional malaise (PEM) or other problems occur whitin 24h after exercise. The participants will once a week be supervised and guided individually by a physioherapist. Participants will, on a weekly basis, complete a training diary regarding their physical activity and training intensity in which they report any setbacks or adverse events.

Measurements of both groups (control and intervention) will be repeated after completion of a period of 16 weeks and longitudinal follow-up at 6 and 12 months.

Eligibility criteria: Inclusion Criteria:

* Adults (\>18 years) diagnosed with POTS (by a cardiologist) post COVID-19 condition.

Exclusion Criteria:

* known pregnancy, cancer, already ongoing intervention of individual tailored physical exercise as the intervention (specific for POTS), unable to perform measurements and/or intervention

Primary outcomes:
measure: Change in time in upright position and steps per day
timeFrame: through study completion, an average of 1 year
measure: Change in Health-Related Quality of Life (HRQoL)
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: Change in walking distance during 6 minute walk test
timeFrame: through study completion, an average of 1 year
measure: Change in oxygen saturation during 6 minute walk test
timeFrame: through study completion, an average of 1 year
measure: Change in dyspnea during 6 minute walk test
timeFrame: through study completion, an average of 1 year
measure: Change in leg fatigue during 6 minute walk test
timeFrame: through study completion, an average of 1 year
measure: Change in exertion during 6 minute walk test
timeFrame: through study completion, an average of 1 year
measure: Change in heart rate during 6 minute walk test
timeFrame: through study completion, an average of 1 year
measure: Change in Self-reported POTS-symptoms
timeFrame: through study completion, an average of 1 year
measure: Change in Anxiety - Generalised Anxiety Disorder 7-item scale
timeFrame: through study completion, an average of 1 year
measure: Change in Depression - Patient Health Questionnaire-9
timeFrame: through study completion, an average of 1 year
measure: Change in Fatigue
timeFrame: through study completion, an average of 1 year
measure: Change in Self-reported outcome measure of physical function
timeFrame: through study completion, an average of 1 year
measure: Change in blood pressure during Active standing test
timeFrame: through study completion, an average of 1 year
measure: Change in heart rate response during Active standing test
timeFrame: through study completion, an average of 1 year
measure: Change in oxygen saturation during Active standing test
timeFrame: through study completion, an average of 1 year
measure: Change in respiratory rate during Active Standing Test
timeFrame: through study completion, an average of 1 year
measure: Change in dyspnea during Active standing test
timeFrame: through study completion, an average of 1 year
measure: Change in leg fatigue during Active Standing Test
timeFrame: through study completion, an average of 1 year
measure: Change in exertion during Active standing test
timeFrame: through study completion, an average of 1 year
measure: Change in Physical activity
timeFrame: through study completion, an average of 1 year
measure: Change in orthostatic symptoms
timeFrame: through study completion, an average of 1 year
measure: Change in insomnia
timeFrame: through study completion, an average of 1 year
measure: Change in Workability
timeFrame: through study completion, an average of 1 year
measure: Change in muscle strength
timeFrame: through study completion, an average of 1 year
measure: Change in post-exertional-Malaise (PEM)
timeFrame: through study completion, an average of 1 year
measure: Change in pharmacological treatment of POTS
timeFrame: through study completion, an average of 1 year
measure: Compliance to intervention
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
Study officials:
affiliation: Karolinska Institutet
name: Malin Nygren-Bonnier, PhD
role: PRINCIPAL_INVESTIGATOR
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