The Effect of Physical Activity on Postural Orthostatic Tachycardia Syndrome (POTS)

Postural orthostatic tachycardia syndrome (POTS) is a disorder of unknown origin characterized by orthostatic intolerance and increased heart rate (HR) of ≥ 30 beats/minute during orthostasis in the absence of orthostatic hypotension. In addition to the orthostatic intolerance and tachycardia, patients with POTS experience several debilitating symptoms including light-headedness, nausea, blurred vision, fatigue, mental confusion ("brain-fog"), chest pain and gastrointestinal problems. Several potential underlying mechanisms have been suggested for POTS including autonomic denervation, hypovolemia, hyperadrenergic stimulation and autoantibodies against adrenergic receptors. However, none of these proposed mechanisms has yet led to an effective treatment. Physical activity is recommended as a complimentary treatment in POTS in international guidelines. However, less is known regarding how physical activity could successfully be implemented in clinical practice in patients with POTS. Thus, in the current study, we aim to assess the effect of a 16-week specialized physical activity program in POTS.

Study Overview

• Status: Recruiting
• Conditions: POTS - Postural Orthostatic Tachycardia Syndrome
• Intervention / Treatment: Other: Training program

Detailed Description

A total of 200 patients diagnosed with POTS are asked to participate in the study. The study will be conducted as a cross over study. All POTS patients will continuously be randomized into two groups (Group A and B). Group A will first start the training program and when the training program is finished group B will start the training program. While each group is not performing the training program the patients will be encouraged to physical activity according to their own abilities.

Prior to start of the training program a special POTS questionnaire, the orthostatic hypotension questionnaire and SF-36 (general health questionnaire) will be completed by the participants. Orthostatic tests are performed during 10 minutes, measuring heart rate and blood pressure after 0, 1, 3, and, if possible, 10 minutes of standing. On a separate occasion, patients will perform a maximal biking exercise test, while noting symptoms, degree of exertion, achieved effect, pulse and blood pressure reaction. Following this initial evaluation, the training program will be performed during a total time of 16 weeks, which may be non-consecutive but within 6 months in total. The training program consists of 2-3 visits per week, and 60 minutes per visit. The training may be performed on specialized exercise bicycles in supine position or upright position depending on the severity of POTS symptoms. These exercises will be done under the supervision of physiotherapists with special interest in POTS. After the final training session the POTS questionnaire, the orthostatic hypotension questionnaire and SF-36 will be completed once again. In addition, orthostatic tests and maximal biking exercise test will be performed on a separate occasion soon after the last training session. The POTS questionnaire, the orthostatic hypotension questionnaire, SF-36, hemodynamics and exercise capacity will be compared before and after the 16-weeks training program.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Isabella Kharraziha, MD; Phone Number: +46702941194; Email: isabella.kharraziha@med.lu.se
• Study Contact Backup: Name: Viktor Hamrefors, MD, PhD; Phone Number: +46703996529; Email: viktor.hamrefors@med.lu.se

Study Locations

• Sweden
  • Malmö, Sweden, 214 28
    • Recruiting
    • Skånes Universitetssjukhus Malmö, Department of Cardiology
    • Contact: Isabella Kharraziha, MD; Phone Number: +46702941194; Email: isabella.kharraziha@med.lu.se
    • Contact: Viktor Hamrefors, MD, PhD; Email: viktor.hamrefors@med.lu.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients diagnosed with POTS who have given written informed consent for participation in the study.

Exclusion Criteria:

• Patients with myalgic encephalomyelitis are excluded from the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A - Supervised exercise first; All POTS patients will continuously be randomized into two groups (Group A and B). Group A will first start the training program and when the training program is finished group B will start the training program. While each group is not performing the training program the patients will be encouraged to physical activity according to their own abilities. Results from questionnaires, orthostatic tests and maximal biking tests will be compared between group A and B as well as within each group.	Other: Training program; A 16-week training program consisting of 2-3 visits per week, and 60 minutes per visit. The program will be done as group exercise under supervision from physiotherapists and/or physicians with special interest in POTS.
Active Comparator: Group B - Self-instruction exercise first; See above.	Other: Training program; A 16-week training program consisting of 2-3 visits per week, and 60 minutes per visit. The program will be done as group exercise under supervision from physiotherapists and/or physicians with special interest in POTS.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
POTS questionnaire	Subjective symptoms evaluated according to the Malmö POTS Symptom Score which has previously been described (Spahic et al. 2022). The questionnaire is based on patients' own perception of 12 commonly reported symptoms: five cardiac symptoms (palpitations, dizziness, presyncope, dyspnoea and chest pain) and seven non-cardiac symptoms (gastrointestinal symptoms, insomnia, concentration difficulties, headache, myalgia, nausea and fatigue) during the previous 7 days, graded on a scale from 0 (no symptoms) to 10 (very pronounced symptoms). The score ranges from 0 to a maximum score of 120 points.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Orthostatic hypotension questionnaire	Subjective symptoms evaluated according to the orthostatic hypotension questionnaire (OHQ). The OHQ is a questionnaire that has been previously validated and used for orthostatic hypotension but has also been used for quantification of POTS-related symptoms. Further details on the OHQ has previously been described in Kharraziha et al (2020).	12 months
SF-36	Evaluation of 36-item Short Form Health Survey (SF-36). The SF-36 is a 36-item patient-reported questionnaire covering eight health domains: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. Scores for each domain range from 0 to 100, with a higher score defining a more favorable health state.	12 months
Orthostatic tests	Hemodynamic measurements (pulse reaction) during orthostatic testing	12 months
Maximal biking exercise	Physical capacity measured in watts	12 months

Collaborators and Investigators

• Sponsor: Lund University
• Collaborators: Region Skane
• Investigators: Study Director: Viktor Hamrefors, MD, PhD, Department of Clinical Sciences, Lund University; Department of Cardiology Skåne University Hospital

Publications and helpful links

General Publications

• Winker R, Barth A, Bidmon D, Ponocny I, Weber M, Mayr O, Robertson D, Diedrich A, Maier R, Pilger A, Haber P, Rudiger HW. Endurance exercise training in orthostatic intolerance: a randomized, controlled trial. Hypertension. 2005 Mar;45(3):391-8. doi: 10.1161/01.HYP.0000156540.25707.af. Epub 2005 Feb 7.
• Fu Q, Vangundy TB, Galbreath MM, Shibata S, Jain M, Hastings JL, Bhella PS, Levine BD. Cardiac origins of the postural orthostatic tachycardia syndrome. J Am Coll Cardiol. 2010 Jun 22;55(25):2858-68. doi: 10.1016/j.jacc.2010.02.043.
• George SA, Bivens TB, Howden EJ, Saleem Y, Galbreath MM, Hendrickson D, Fu Q, Levine BD. The international POTS registry: Evaluating the efficacy of an exercise training intervention in a community setting. Heart Rhythm. 2016 Apr;13(4):943-50. doi: 10.1016/j.hrthm.2015.12.012. Epub 2015 Dec 9.
• Shibata S, Fu Q, Bivens TB, Hastings JL, Wang W, Levine BD. Short-term exercise training improves the cardiovascular response to exercise in the postural orthostatic tachycardia syndrome. J Physiol. 2012 Aug 1;590(15):3495-505. doi: 10.1113/jphysiol.2012.233858. Epub 2012 May 28.
• Kharraziha I, Axelsson J, Ricci F, Di Martino G, Persson M, Sutton R, Fedorowski A, Hamrefors V. Serum Activity Against G Protein-Coupled Receptors and Severity of Orthostatic Symptoms in Postural Orthostatic Tachycardia Syndrome. J Am Heart Assoc. 2020 Aug 4;9(15):e015989. doi: 10.1161/JAHA.120.015989. Epub 2020 Jul 30.
• Spahic JM, Hamrefors V, Johansson M, Ricci F, Melander O, Sutton R, Fedorowski A. Malmo POTS symptom score: Assessing symptom burden in postural orthostatic tachycardia syndrome. J Intern Med. 2023 Jan;293(1):91-99. doi: 10.1111/joim.13566. Epub 2022 Sep 16.
• Laucis NC, Hays RD, Bhattacharyya T. Scoring the SF-36 in Orthopaedics: A Brief Guide. J Bone Joint Surg Am. 2015 Oct 7;97(19):1628-34. doi: 10.2106/JBJS.O.00030.

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2022
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: September 21, 2022
• First Submitted That Met QC Criteria: September 23, 2022
• First Posted (Actual): September 26, 2022

Study Record Updates

• Last Update Posted (Actual): May 30, 2025
• Last Update Submitted That Met QC Criteria: May 26, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Treatment; Exercise; POTS; Training programme; Orthostatic intolerance
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Nervous System Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Disease; Arrhythmias, Cardiac; Primary Dysautonomias; Autonomic Nervous System Diseases; Orthostatic Intolerance; Syndrome; Tachycardia; Postural Orthostatic Tachycardia Syndrome
• Other Study ID Numbers: POTS-phys

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Due to legal and ethical reasons.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No