POTS-CFS Study: Orthostatic Intolerance in the Context of Pediatric ME/CFS

Study Overview
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Brief Summary
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Pilot-case-control study on exertion and orthostatic intolerance of adolescents with myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) compared to age-matched healthy controls (HC).

Detailed Description
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ME/CFS is a complex disease. Symptoms include orthostatic intolerance (OI) such as postural tachycardia syndrome (PoTS). PoTS in ME/CFS can significantly impair everyday function and social participation. Yet, data in affected adolescents are rare and inconsistent. This pilot-case-control study study aimed at characterizing OI in adolescents aged 14-17 years with ME/CFS and age-adapted HC, comparing the results with other clinical features of both such as exertion intolerance, fatigue, and health-related quality of life, and suggesting a standardized tool for diagnostics. ME/CFS was diagnosed according to the Clinical Canadian Criteria (CCC 2003), criteria of the former Institute of Medicine (IOM 2015), the diagnostic work sheet developed by Rowe 2017, and/or the pediatric case suggested by Jason 2006. Questionnaires were used to evaluate symptoms (e.g. post-exertional malaise, fatigue, anxiety, depression), and health-related quality of life. A standardized specific interview was performed to assess the medical history of OI (HOI). Heart rate (HR) and blood pressure were evaluated every minute during a passive 10-min standing test (NASA lean test) in the morning with empty stomach and without morning medication. Data were evaluated according to the PoTS criteria defined in 2019 at the National Institutes of Health Expert Consensus Meeting and by the International Classification of Diseases (ICD-11) (8D89.2). Frequency and type of OI, including PoTS, were examined in both groups and outcomes compared to parameters from questionnaires. Based on the results, novel standards for OI diagnostics were suggested.

Official Title
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POTS-CFS Study: A Case-Control Study on Exertion and Orthostatic Intolerance in the Context of Pediatric ME/CFS

Conditions
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Chronic Fatigue Syndrome in Adolescence, Postural Orthostatic Tachycardia Syndrome, Orthostatic Intolerance

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cases (ME/CFS): - ME/CFS diagnosed by the indicated clinical criteria Healthy Controls clinically healthy no known underlying disease no prescription medication (except contraception) Exclusion Criteria: Any contraindication for NASA lean test (cardiac failure, severe aortic stenosis, inability to stand) pregnancy breastfeeding.

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ME/CFS<br>ME/CFS: adolescents aged 14-17 years, fulfilling diagnostic criteria for ME/CFS according to Rowe e 2017, Jason 2006, CCC 2003, and/ or IOM 2015 at the time of recruitment. Methods: Semi-structured interview, questionnaires, passive 10-minute standing test (NASA lean test), blood sampling. | |
| Healthy Controls (HC)<br>HC: adolescents aged 14-17, clinically healthy without any known underlying disease and with no prescription drugs (except contraception). Methods: Semi-structured interview, questionnaires, passive 10-minute standing test (NASA lean test), blood sampling. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart Rate during Passive 10-min. standing test | Heart rate during Passive 10-Min. standing test (NASA lean test) | one time point during study from study start until study completion, approximately 1 year | 
| Blood Pressure during Passive 10-min. standing test | blood pressure, pulse pressure (calculated by systolic and diastolic blood pressure) during Passive 10-Min. standing test (NASA lean test) | one time point during study from study start until study completion, approximately 1 year | 
| Symptoms during Passive 10-Min. standing test | Symptoms during Passive 10-Min. standing test (NASA lean test): Yes/No | one time point during study from study start until study completion, approximately 1 year | 
| O2-Saturation during Passive 10-Min. standing test | O2-Saturation during Passive 10-Min. standing test (NASA lean test) | one time point during study from study start until study completion, approximately 1 year | 
| Presence of Orthostatic Intolerance: Semistructured Interview | Semistructured Interview, History of Orthostatic Intolerance (OI): Yes/No | one time point during study from study start until study completion, approximately 1 year | 
| Number of orthostatic Symptoms: Semistructured Interview | Semistructured Interview, Number of Symptoms | one time point during study from study start until study completion, approximately 1 year | 
| Number of participants with a diagnosis of PoTS, Orthostatic Intolerance and related diagnoses | History of OI and Nasa lean test together result in an orthostatic diagnosis, Fulfilling of PoTS-Criteria at study visit is evaluated | one time point during study from study start until study completion, approximately 1 year | 
| Presence of ME/CFS-specific Symptoms (Munich Berlin Symptom Questionnaire) | Questionnaire: number of relevant symptoms. Likert Scale 0-4 of severity and frequency for each symptom: A symptom is relevant with a severity and frequency of each at least 2 on the Likert Scale. Minimum: 0 relevant symptoms (best), Maximum: 60 relevant symptoms (worst). | one time point during study from study start until study completion, approximately 1 year | 
| Presence of Post-exertional malaise (DePaul Symptom Questionnaire -Post exertional Malaise: DSQ-PEM) | Questionnaire, Binary Outcome: Post-exertional Malaise Yes/No | one time point during study from study start until study completion, approximately 1 year | 
| Self-estimated level of Quality of Life: EQ-5D-5L: Index | Questionnaire: Index (0 worst - 1 best) | one time point during study from study start until study completion, approximately 1 year | 
| Self-estimated level of Quality of Life: EQ-5D-5L: Visual Analog Scale | Visual Analog Scale (0 worst - 100 best) | one time point during study from study start until study completion, approximately 1 year | 
| Screening via Public Health Questionnaire-4 (PHQ-4) | Ultra-Short-4-item-Screening for Anxiety/Depression: Scale (0 Symptom occurs never - 3 Symptom occurs almost every day) | one time point during study from study start until study completion, approximately 1 year | 
| Malmö PoTS Score (MAPS) | Orthostatic Symptoms Severity, Scale (0 no symptom burden - 120 highest symptom burden) | one time point during study from study start until study completion, approximately 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of serum antibodies against EBV | Levels of Autoantibodies at study visit | one time point during study from study start until study completion, approximately 1 year | 
| Levels of serum antibodies against SARS-CoV-2 | Levels of autoantibodies at study visit | one time point during study from study start until study completion, approximately 1 year | 
| Levels of serum autoantibodies | Levels of autoantibodies at study visit | one time point during study from study start until study completion, approximately 1 year |