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

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

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).

Study Overview

• Status: Completed
• Conditions: Orthostatic Intolerance; Postural Orthostatic Tachycardia Syndrome; Chronic Fatigue Syndrome in Adolescence

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 80804
      • MRI Chronic Fatigue Center for Young People (MCFC) Children's Hospital, Technical University of Munich & Munich Municipal Hospital Munich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adolescents with ME/CFS and healthy controls

Description

Inclusion Criteria:

1. Cases (ME/CFS):

   - ME/CFS diagnosed by the indicated clinical criteria

2. 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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
ME/CFS; 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); 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?

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

Collaborators and Investigators

• Sponsor: Technical University of Munich
• Collaborators: University Hospital, Aachen

Publications and helpful links

Helpful Links

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Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2021
• Primary Completion (Actual): November 22, 2022
• Study Completion (Actual): November 22, 2022

Study Registration Dates

• First Submitted: August 16, 2023
• First Submitted That Met QC Criteria: September 22, 2023
• First Posted (Actual): September 26, 2023

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 22, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Neurologic Manifestations; Disease; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Autonomic Nervous System Diseases; Primary Dysautonomias; Encephalomyelitis; Neuroinflammatory Diseases; Syndrome; Tachycardia; Fatigue Syndrome, Chronic; Postural Orthostatic Tachycardia Syndrome; Orthostatic Intolerance
• Other Study ID Numbers: POTS-CFS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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