Postural Orthostatic Tachycardia SyndromeNCT05877534
Effects of Individual Tailored Physical Exercise in Patients With POTS After COVID-19 - a Randomized Controlled Study
A study testing Individual tailored exercise in people with Postural Orthostatic Tachycardia Syndrome and COVID-19, run by Karolinska Institutet at 1 site in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Postural Orthostatic Tachycardia Syndrome, COVID-19, Post COVID-19 Condition
- What is being tested?
- Individual tailored exercise
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteSweden
- Study dates
- 25 May 2023to 1 Nov 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults (>18 years) diagnosed with POTS (by a cardiologist) post COVID-19 condition.
Who cannot join
- known pregnancy, cancer, already ongoing intervention of individual tailored physical exercise as the intervention (specific for POTS), unable to perform measurements and/or intervention
Trial locations and contacts
1 site in 1 country.
About this 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
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.
Read more
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.
Read the 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.
- Conditions
- Postural Orthostatic Tachycardia Syndrome, COVID-19, Post COVID-19 Condition, Post-Acute COVID-19 Syndrome
- Being tested
- Individual tailored exercise
- Medical subject headings
- Postural Orthostatic Tachycardia Syndrome, COVID-19, Post-Acute COVID-19 Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Individual tailored exerciseOther
A 16 week period of progressive exercise, supervised by a physiotherapist once a week.
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | A 16 week period of exercise, supervised by a physiotherapist once a week. The exercise should be individually tailored from a programme based on a previous feasibility study. The program consist of exercises both to improve endurance and muscle strength. Progression and adjustments of time and position will be performed during the intervention period based any symptoms the participant exhibits. Progression should be halted if the participant experience PEM or other symptoms within >24hours after last exercise. The participants will also recieve standard care during the intervention period. Standard care includes (but not restricted to) information about POTS and lifestyle changes that may effect the symptoms, advice about fluid intake and nutrition, compression garments, pharmacological interventions etc. Receives: Other: Individual tailored exercise |
| Control | No intervention | 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 fluid intake and nutrition, compression garments, pharmacological interventions etc. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in time in upright position and steps per day
Measured with two accelerometers, one attached to the chest and one to the lower limbs, to measure time (hours, minutes) in upright position
Measured: through study completion, an average of 1 year
Change in Health-Related Quality of Life (HRQoL)
Measured with EuroQualityOf Life 5 dimensions questionnaire (EQ-5D-5L), which is an instrument that evaluates the generic quality of life. EQ-5D includes a descriptive system, which comprises 5 dimensions of health: mobility, selfcare, usual activities, pain/discomfort, and anxiety/depression. A descriptive index-score between 0-1, higher score indicates higher HRQoL. EQ-5D also includes a visual analog scale (VAS), which records the respondent's self-rated health status on a graduated (0-100) scale, with higher scores for higher HRQoL.
Measured: through study completion, an average of 1 year
Secondary outcomes (26)
Change in walking distance during 6 minute walk test
Change in walking distance measured in meters during 6 minutes walk test (6MWT)
Measured: through study completion, an average of 1 year
Change in oxygen saturation during 6 minute walk test
Change in the lowest oxygen saturation level measured in percentage (%) with pulse oximetry during 6 minute walk test
Measured: through study completion, an average of 1 year
Change in dyspnea during 6 minute walk test
Change in perceived dyspnea measured with Borg Category-Ratio scale (Borg CR-10) at the end of 6 minute walk test. Borg CR-10 ranging between 0-10. The higher the score, the higher the dyspnea.
calculated by subtracting the oxygen level at rest before the test with the lowest level during the test.
Measured: through study completion, an average of 1 year
Change in leg fatigue during 6 minute walk test
Change in perceived leg fatigue measured with Borg CR-10 at the end of 6 minute walk test. Borg CR-10 ranging between 0-10. The higher the score, the higher the leg fatigue. test. Borg CR-10 ranging between 0-10. The higher the score, the higher the dyspnea.
calculated by subtracting the oxygen level at rest before the test with the lowest level during the test.
Measured: through study completion, an average of 1 year
Change in exertion during 6 minute walk test
Change in perceived exertion measured with Borg Rating of Perceived Exertion (Borg RPE) at the end of 6 minutes walk test. Borg RPE ranging between 6-20. The higher the score, the higher the exertion.
Measured: through study completion, an average of 1 year
Change in heart rate during 6 minute walk test
Change in the highest heart rate measured in beats per minute with pulseoxymeter during 6 minute walk test
Measured: through study completion, an average of 1 year
Change in Self-reported POTS-symptoms
Measured with Malmö-POTS-questionnaire (MaPS), which is a self assessment tool examining common symptoms in POTS. MaPS consists of 12 items. Patients are asked to rate symptoms on a scale from 0-10 on each item. 0 i= no symptom and 10 = worst imaginable. Total score ranging from 0-120. Higher score indicates more POTS-symptoms.
Measured: through study completion, an average of 1 year
Change in Anxiety - Generalised Anxiety Disorder 7-item scale
Measured with Generalised Anxiety Disorder 7-item scale (GAD-7) which is a self assessment tool. Total score ranging from 0-21. Higher score indicates higher anxiety.
Measured: through study completion, an average of 1 year
Change in Depression - Patient Health Questionnaire-9
Measured with Patient Health Questionnaire-9 (PHQ-9). PHQ-9 which contains 9 items. Total score ranges from 0 to 27. Higher score indicate more severe depression symptoms
Measured: through study completion, an average of 1 year
Change in Fatigue
Measured with Fatigue Severity Scale (FSS), which is a 9-item scale that measures the severity of fatigue and its effect on a person's activities and lifestyle in patients with a variety of disorders. Total score ranging from 9-63. The higher the score, the more severe the fatigue is. Fatigue also measured with Mental Fatigue Scale (MFS), which is a 15-item scale that measures the severity of mental fatigue. Total score ranging from 0-44. The higher the score, the more severe the fatigue is.
Measured: through study completion, an average of 1 year
Change in Self-reported outcome measure of physical function
Measured with Patient Specific Functional Scale (PSFS), a questionnaire that can be used to quantify activity limitation and measure functional outcome for patients. Patients are asked to identify three to five important activities they are unable to perform or are having difficulty with because of their problem. In addition to identifying the activities, patients are asked to rate, on a scale ranging from 0-10, the current level of difficulty associated with each activity. The higher the score, the less difficulty to perform the activity
Measured: through study completion, an average of 1 year
Change in blood pressure during Active standing test
Measured with Active standing test according to a specific protocol with measurements of responses in systolic and diastolic blood pressure after getting up to standing from the supine position
Measured: through study completion, an average of 1 year
Change in heart rate response during Active standing test
Measured with Active standing test according to a specific protocol with measurements of responses in heart rate after getting up to standing from the supine position.
Measured: through study completion, an average of 1 year
Change in oxygen saturation during Active standing test
Measured with Active standing test according to a specific protocol with measurements of responses in oxygen saturation, measured with pulse oximetry, after getting up to standing from the supine position.
Measured: through study completion, an average of 1 year
Change in respiratory rate during Active Standing Test
Change in respiratory rate, measured in number of breaths/min before and after the Active Standing Test
Measured: through study completion, an average of 1 year
Change in dyspnea during Active standing test
Measured with Active standing test according to a specific protocol with measurements of responses in perceived dyspnea measured with Borg CR-10 scale after getting up to standing from the supine position.
Measured: through study completion, an average of 1 year
Change in leg fatigue during Active Standing Test
Change in perceived leg fatigue measured with Borg CR-10 before, during and at the end of Active Standing Test.
Measured: through study completion, an average of 1 year
Change in exertion during Active standing test
Measured with Active standing test according to a specific protocol with measurements of responses in perceived exertion with Borg RPE scale after getting up to standing from the supine position.
Measured: through study completion, an average of 1 year
Change in Physical activity
Measured with Frändin/Grimby activity scale, which is a self-assessment scale about current levels of physical activity, ranging from 1 to 6. The higher the score, the higher the level of physical activity
Measured: through study completion, an average of 1 year
Change in orthostatic symptoms
Assessed with the Vanderbilt Orthostatic Symptom Scale (VOSS). After the Active standing test (AST) the participant uses a self-assessment questionnaire about orthostatic symptoms prominent during the Active standing test (performed according to a specific protocol with measurements of responses in systolic and diastolic blood pressure after getting up to standing from the supine position). The scale range from 0=no symptoms, to 10=worst imaginable symptoms. The scale includes 9 items regarding orthostatic symptoms and the higher the score, the higher level of symptoms during the orthostatic test.
Measured: through study completion, an average of 1 year
Change in insomnia
Measured with Insomnia Severity Index (ISI), a 7-item questionnaire. Score between 0-28, with higher score indication a more severe insomnia.
Measured: through study completion, an average of 1 year
Change in Workability
Measured in percentage of full time work, ranging from 0-100%
Measured: through study completion, an average of 1 year
Change in muscle strength
Measured with the wireless microFET®2 Digital Handheld Dynamometer muscle tester. measurements of isometric muscle strength will be carried out on muscles in the lower extremity according to guidelines.
Measured: through study completion, an average of 1 year
Change in post-exertional-Malaise (PEM)
Measured by the quiestionnaire; DePaul Symptom Questionnaire-Post Exertional Malaise Short-form (DSQ-PEM). DSQ-PEM is a 10 item questionnaire that includes scoring of frequency and severity of PEM and indicate if ME/CFS may be present. Higher score indicates more severe PEM.
Measured: through study completion, an average of 1 year
Change in pharmacological treatment of POTS
Assessed by gathering information from the participants and from their medical journal of what type of pharmacological treatment they're in need of and the dose.
Measured: through study completion, an average of 1 year
Compliance to intervention
Assessed by participant diaries during 16weeks
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2023
- Study start25 May 2023
- Primary completion1 Oct 2025
- Study completion1 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Postural Orthostatic Tachycardia SyndromeStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- Karolinska University Hospital
- Responsible party
- Principal investigator, Malin Nygren-Bonnier, Karolinska Institutet
- Investigators
- Malin Nygren-Bonnier, PhD, Principal investigator, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05877534
- Sponsor's protocol ID
- RCT-POTS-ReCov
- Status last verified
- Jan 2026
- First submitted
- 24 May 2023
- Last updated
- 15 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fu Q, Levine BD. Exercise and non-pharmacological treatment of POTS. Auton Neurosci. 2018 Dec;215:20-27. doi: 10.1016/j.autneu.2018.07.001. Epub 2018 Jul 4.
PubMed 30001836Crook H, Raza S, Nowell J, Young M, Edison P. Long covid-mechanisms, risk factors, and management. BMJ. 2021 Jul 26;374:n1648. doi: 10.1136/bmj.n1648.
PubMed 34312178Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, Cook JR, Nordvig AS, Shalev D, Sehrawat TS, Ahluwalia N, Bikdeli B, Dietz D, Der-Nigoghossian C, Liyanage-Don N, Rosner GF, Bernstein EJ, Mohan S, Beckley AA, Seres DS, Choueiri TK, Uriel N, Ausiello JC, Accili D, Freedberg DE, Baldwin M, Schwartz A, Brodie D, Garcia CK, Elkind MSV, Connors JM, Bilezikian JP, Landry DW, Wan EY. Post-acute COVID-19 syndrome. Nat Med. 2021 Apr;27(4):601-615. doi: 10.1038/s41591-021-01283-z. Epub 2021 Mar 22.
PubMed 33753937Fedorowski A. Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management. J Intern Med. 2019 Apr;285(4):352-366. doi: 10.1111/joim.12852. Epub 2018 Nov 23.
PubMed 30372565Johansson M, Stahlberg M, Runold M, Nygren-Bonnier M, Nilsson J, Olshansky B, Bruchfeld J, Fedorowski A. Long-Haul Post-COVID-19 Symptoms Presenting as a Variant of Postural Orthostatic Tachycardia Syndrome: The Swedish Experience. JACC Case Rep. 2021 Apr;3(4):573-580. doi: 10.1016/j.jaccas.2021.01.009. Epub 2021 Mar 10.
PubMed 33723532Stahlberg M, Reistam U, Fedorowski A, Villacorta H, Horiuchi Y, Bax J, Pitt B, Matskeplishvili S, Luscher TF, Weichert I, Thani KB, Maisel A. Post-COVID-19 Tachycardia Syndrome: A Distinct Phenotype of Post-Acute COVID-19 Syndrome. Am J Med. 2021 Dec;134(12):1451-1456. doi: 10.1016/j.amjmed.2021.07.004. Epub 2021 Aug 11.
PubMed 34390682Arnold AC, Ng J, Raj SR. Postural tachycardia syndrome - Diagnosis, physiology, and prognosis. Auton Neurosci. 2018 Dec;215:3-11. doi: 10.1016/j.autneu.2018.02.005. Epub 2018 Feb 28.
PubMed 29523389Benrud-Larson LM, Dewar MS, Sandroni P, Rummans TA, Haythornthwaite JA, Low PA. Quality of life in patients with postural tachycardia syndrome. Mayo Clin Proc. 2002 Jun;77(6):531-7. doi: 10.4065/77.6.531.
PubMed 12059122
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05877534
- Acronym / sponsor ID
- RCT-POTS-ReCov
- Conditions
- Postural Orthostatic Tachycardia Syndrome, COVID-19, Post COVID-19 Condition, Post-Acute COVID-19 Syndrome
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- Karolinska University Hospital
- Study start
- 25 May 2023 (actual)
- Primary completion
- 1 Oct 2025 (actual)
- Study completion
- 1 Nov 2026 (estimated)
- First posted
- 26 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Other: Individual tailored exerciseA 16 week period of exercise, supervised by a physiotherapist once a week. The exercise should be individually tailored from a programme based on a previous feasibility study. The program consist of exercises both to improve endurance and muscle strength. Progression and adjustments of time and position will be performed during the intervention period based any symptoms the participant exhibits. Progression should be halted if the participant experience PEM or other symptoms within >24hours after last exercise. The participants will also recieve standard care during the intervention period. Standard care includes (but not restricted to) information about POTS and lifestyle changes that may effect the symptoms, advice about fluid intake and nutrition, compression garments, pharmacological interventions etc. |
| Control | No intervention | –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 fluid intake and nutrition, compression garments, pharmacological interventions etc. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Adults (>18 years) diagnosed with POTS (by a cardiologist) post COVID-19 condition.
Key exclusion criteria (1 listed)
- known pregnancy, cancer, already ongoing intervention of individual tailored physical exercise as the intervention (specific for POTS), unable to perform measurements and/or intervention
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Individual tailored exerciseA 16 week period of progressive exercise, supervised by a physiotherapist once a week. | Other | Intervention |
Primary outcome
Change in time in upright position and steps per day
Time frame: through study completion, an average of 1 year
Measured with two accelerometers, one attached to the chest and one to the lower limbs, to measure time (hours, minutes) in upright position
Change in Health-Related Quality of Life (HRQoL)
Time frame: through study completion, an average of 1 year
Measured with EuroQualityOf Life 5 dimensions questionnaire (EQ-5D-5L), which is an instrument that evaluates the generic quality of life. EQ-5D includes a descriptive system, which comprises 5 dimensions of health: mobility, selfcare, usual activities, pain/discomfort, and anxiety/depression. A descriptive index-score between 0-1, higher score indicates higher HRQoL. EQ-5D also includes a visual analog scale (VAS), which records the respondent's self-rated health status on a graduated (0-100) scale, with higher scores for higher HRQoL.
26 secondary outcomes
Change in walking distance during 6 minute walk test
Time frame: through study completion, an average of 1 year
Change in oxygen saturation during 6 minute walk test
Time frame: through study completion, an average of 1 year
Change in dyspnea during 6 minute walk test
Time frame: through study completion, an average of 1 year
Change in leg fatigue during 6 minute walk test
Time frame: through study completion, an average of 1 year
Change in exertion during 6 minute walk test
Time frame: through study completion, an average of 1 year
Change in heart rate during 6 minute walk test
Time frame: through study completion, an average of 1 year
Change in Self-reported POTS-symptoms
Time frame: through study completion, an average of 1 year
Change in Anxiety - Generalised Anxiety Disorder 7-item scale
Time frame: through study completion, an average of 1 year
Change in Depression - Patient Health Questionnaire-9
Time frame: through study completion, an average of 1 year
Change in Fatigue
Time frame: through study completion, an average of 1 year
Change in Self-reported outcome measure of physical function
Time frame: through study completion, an average of 1 year
Change in blood pressure during Active standing test
Time frame: through study completion, an average of 1 year
Change in heart rate response during Active standing test
Time frame: through study completion, an average of 1 year
Change in oxygen saturation during Active standing test
Time frame: through study completion, an average of 1 year
Change in respiratory rate during Active Standing Test
Time frame: through study completion, an average of 1 year
Change in dyspnea during Active standing test
Time frame: through study completion, an average of 1 year
Change in leg fatigue during Active Standing Test
Time frame: through study completion, an average of 1 year
Change in exertion during Active standing test
Time frame: through study completion, an average of 1 year
Change in Physical activity
Time frame: through study completion, an average of 1 year
Change in orthostatic symptoms
Time frame: through study completion, an average of 1 year
Change in insomnia
Time frame: through study completion, an average of 1 year
Change in Workability
Time frame: through study completion, an average of 1 year
Change in muscle strength
Time frame: through study completion, an average of 1 year
Change in post-exertional-Malaise (PEM)
Time frame: through study completion, an average of 1 year
Change in pharmacological treatment of POTS
Time frame: through study completion, an average of 1 year
Compliance to intervention
Time frame: through study completion, an average of 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2026.
- Background: PubMed 30001836Fu Q, Levine BD. Exercise and non-pharmacological treatment of POTS. Auton Neurosci. 2018 Dec;215:20-27. doi: 10.1016/j.autneu.2018.07.001. Epub 2018 Jul 4.
- Background: PubMed 34312178Crook H, Raza S, Nowell J, Young M, Edison P. Long covid-mechanisms, risk factors, and management. BMJ. 2021 Jul 26;374:n1648. doi: 10.1136/bmj.n1648.
- Background: PubMed 33753937Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, Cook JR, Nordvig AS, Shalev D, Sehrawat TS, Ahluwalia N, Bikdeli B, Dietz D, Der-Nigoghossian C, Liyanage-Don N, Rosner GF, Bernstein EJ, Mohan S, Beckley AA, Seres DS, Choueiri TK, Uriel N, Ausiello JC, Accili D, Freedberg DE, Baldwin M, Schwartz A, Brodie D, Garcia CK, Elkind MSV, Connors JM, Bilezikian JP, Landry DW, Wan EY. Post-acute COVID-19 syndrome. Nat Med. 2021 Apr;27(4):601-615. doi: 10.1038/s41591-021-01283-z. Epub 2021 Mar 22.
- Background: PubMed 30372565Fedorowski A. Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management. J Intern Med. 2019 Apr;285(4):352-366. doi: 10.1111/joim.12852. Epub 2018 Nov 23.
- Background: PubMed 33723532Johansson M, Stahlberg M, Runold M, Nygren-Bonnier M, Nilsson J, Olshansky B, Bruchfeld J, Fedorowski A. Long-Haul Post-COVID-19 Symptoms Presenting as a Variant of Postural Orthostatic Tachycardia Syndrome: The Swedish Experience. JACC Case Rep. 2021 Apr;3(4):573-580. doi: 10.1016/j.jaccas.2021.01.009. Epub 2021 Mar 10.
- Background: PubMed 34390682Stahlberg M, Reistam U, Fedorowski A, Villacorta H, Horiuchi Y, Bax J, Pitt B, Matskeplishvili S, Luscher TF, Weichert I, Thani KB, Maisel A. Post-COVID-19 Tachycardia Syndrome: A Distinct Phenotype of Post-Acute COVID-19 Syndrome. Am J Med. 2021 Dec;134(12):1451-1456. doi: 10.1016/j.amjmed.2021.07.004. Epub 2021 Aug 11.
- Background: PubMed 29523389Arnold AC, Ng J, Raj SR. Postural tachycardia syndrome - Diagnosis, physiology, and prognosis. Auton Neurosci. 2018 Dec;215:3-11. doi: 10.1016/j.autneu.2018.02.005. Epub 2018 Feb 28.
- Background: PubMed 12059122Benrud-Larson LM, Dewar MS, Sandroni P, Rummans TA, Haythornthwaite JA, Low PA. Quality of life in patients with postural tachycardia syndrome. Mayo Clin Proc. 2002 Jun;77(6):531-7. doi: 10.4065/77.6.531.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Malin Nygren-Bonnier, PhD principal investigator
Karolinska Institutet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Individual tailored exercise in people with Postural Orthostatic Tachycardia Syndrome and COVID-19, run by Karolinska Institutet at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 15 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in time in upright position and steps per day (time frame: through study completion, an average of 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05877534, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2026.