Mild Water-filtered Infrared-A Whole-body Hyperthermia in Patients With Post-COVID Syndrome (HyPoCo) (HyPoCo)

• ClinicalTrials.gov Identifier: NCT06204458
• Recruitment Status: Recruiting
• First Posted: January 12, 2024
• Last Update Posted: January 12, 2024
• Sponsor: Universität Duisburg-Essen
• Collaborator: Bavarian State Ministry of Health and Care
• Information provided by (Responsible Party): Jost Langhorst, Universität Duisburg-Essen

Tracking Information

• First Submitted Date: January 11, 2024
• First Posted Date: January 12, 2024
• Last Update Posted Date: January 12, 2024
• Estimated Study Start Date: January 8, 2024
• Estimated Primary Completion Date: December 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 11, 2024)

• Multidimensionl Fatigue Inventory (MFI-20) [ Time Frame: Week 0 ]
  An inventory including 20 questions about fatigue-symptoms (each from 1 ("Yes, that is true") to 5 ("No, that is not true")) covering 5 dimensions (general fatigue, physical fatigue, reduced motivation, reduced activity, mental fatigue).
• Multidimensionl Fatigue Inventory (MFI-20) [ Time Frame: Week 3 ]
  An inventory including 20 questions about fatigue-symptoms (each from 1 ("Yes, that is true") to 5 ("No, that is not true")) covering 5 dimensions (general fatigue, physical fatigue, reduced motivation, reduced activity, mental fatigue).

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: January 11, 2024)

• Multidimensionl Fatigue Inventory (MFI-20) [ Time Frame: Week 15 ]
  An inventory including 20 questions about fatigue-symptoms (each from 1 ("Yes, that is true") to 5 ("No, that is not true")) covering 5 dimensions (general fatigue, physical fatigue, reduced motivation, reduced activity, mental fatigue).
• Brief Pain Inventory (BPI) - Intensity of pain (Numeric Rating Scale, NRS) [ Time Frame: Week 0 ]
  An inventory including 15 Items about the intensity of pain (4 items, numeric rating scales from 1 (no pain) to 10 (worst pain imaginable); primary outcome), pain impairment (7 items with NRS from 1-10) and the efficacy of medications/treatments.
• Brief Pain Inventory (BPI) - Intensity of pain (Numeric Rating Scale, NRS) [ Time Frame: Week 3 ]
  An inventory including 15 Items about the intensity of pain (4 items, numeric rating scales from 1 (no pain) to 10 (worst pain imaginable); primary outcome), pain impairment (7 items with NRS from 1-10) and the efficacy of medications/treatments.
• Brief Pain Inventory (BPI) - Intensity of pain (Numeric Rating Scale, NRS) [ Time Frame: Week 15 ]
  An inventory including 15 Items about the intensity of pain (4 items, numeric rating scales from 1 (no pain) to 10 (worst pain imaginable); primary outcome), pain impairment (7 items with NRS from 1-10) and the efficacy of medications/treatments.
• Pittsburgh Sleep quality index (PSQI) [ Time Frame: Week 0 ]
  An inventory including 10 questions (plus subquestions) about the quality of sleep. Most of the questions range from ("Not during the past month" to "thee or more times a week"). The questions can be calculated in seven subscales.
• Pittsburgh Sleep quality index (PSQI) [ Time Frame: Week 3 ]
  An inventory including 10 questions (plus subquestions) about the quality of sleep. Most of the questions range from ("Not during the past month" to "thee or more times a week"). The questions can be calculated in seven subscales.
• Pittsburgh Sleep quality index (PSQI) [ Time Frame: Week 15 ]
  An inventory including 10 questions (plus subquestions) about the quality of sleep. Most of the questions range from ("Not during the past month" to "thee or more times a week"). The questions can be calculated in seven subscales.
• Generic quality of life [ Time Frame: Week 0 ]
  Short Form SF-12 Health Survey Questionnaire; A low total value correlates with a poor quality of life, a higher one with a better one.
• Generic quality of life [ Time Frame: Week 3 ]
  Short Form SF-12 Health Survey Questionnaire; A low total value correlates with a poor quality of life, a higher one with a better one.
• Generic quality of life [ Time Frame: Week 15 ]
  Short Form SF-12 Health Survey Questionnaire; A low total value correlates with a poor quality of life, a higher one with a better one.
• Quality of life (EQ-5D) [ Time Frame: Week 0 ]
  The EQ-5D measures 5 dimensions of quality of life (mobility, self-care, general activities, pain/physical discomfort and anxiety/depression) as well as the general state of health on a VAS from 0-100.
• Quality of life (EQ-5D) [ Time Frame: Week 3 ]
  The EQ-5D measures 5 dimensions of quality of life (mobility, self-care, general activities, pain/physical discomfort and anxiety/depression) as well as the general state of health on a VAS from 0-100.
• Quality of life (EQ-5D) [ Time Frame: Week 15 ]
  The EQ-5D measures 5 dimensions of quality of life (mobility, self-care, general activities, pain/physical discomfort and anxiety/depression) as well as the general state of health on a VAS from 0-100.
• Anxiety and Depression [ Time Frame: Week 0 ]
  Hospital Anxiety and Depression Scale (HADS), 14 items (7 each for depressive symptoms or symptoms of anxiety). The two summated scores of the summated scales HADS-A and HADS-D range between 0 and 21. High scores indicate depressivness and anxiety.
• Anxiety and Depression [ Time Frame: Week 3 ]
  Hospital Anxiety and Depression Scale (HADS), 14 items (7 each for depressive symptoms or symptoms of anxiety). The two summated scores of the summated scales HADS-A and HADS-D range between 0 and 21. High scores indicate depressivness and anxiety.
• Anxiety and Depression [ Time Frame: Week 15 ]
  Hospital Anxiety and Depression Scale (HADS), 14 items (7 each for depressive symptoms or symptoms of anxiety). The two summated scores of the summated scales HADS-A and HADS-D range between 0 and 21. High scores indicate depressivness and anxiety.
• G-EEE (Generic Rating for Treatment pre-experiences, Treatment Expectations and Treatment effects) [ Time Frame: Week 0 ]
  A non validated inventory including 11 items measuring pre-experiences, treatment expectations and treatment effects.
• G-EEE (Generic Rating for Treatment pre-experiences, Treatment Expectations and Treatment effects) [ Time Frame: Week 3 ]
  A non validated inventory including 11 items measuring pre-experiences, treatment expectations and treatment effects.
• G-EEE (Generic Rating for Treatment pre-experiences, Treatment Expectations and Treatment effects) [ Time Frame: Week 15 ]
  A non validated inventory including 11 items measuring pre-experiences, treatment expectations and treatment effects.
• Perceived Stress (PSS-10) [ Time Frame: Week 0 ]
  Perceived stress is determined using the Perceived Stress Scale (PSS). The PSS is an international standard instrument for recording subjective stress levels. The official German 10-item version is used in the study.
• Perceived Stress (PSS-10) [ Time Frame: Week 3 ]
  Perceived stress is determined using the Perceived Stress Scale (PSS). The PSS is an international standard instrument for recording subjective stress levels. The official German 10-item version is used in the study.
• Perceived Stress (PSS-10) [ Time Frame: Week 15 ]
  Perceived stress is determined using the Perceived Stress Scale (PSS). The PSS is an international standard instrument for recording subjective stress levels. The official German 10-item version is used in the study.
• Canadian consensus criteria (CCC) [ Time Frame: Week 0 ]
  This is a questionnaire for the diagnosis of CFS/ME (Carruthers et al. 2003). This definition scheme can be used to clinically confirm the diagnosis of CFS/ME. The list of criteria includes the following symptom complexes: Fatigue, exercise intolerance (PEM), sleep disturbances, pain, neurological or cognitive symptoms, autonomic symptoms, neuroendocrine symptoms and immunological symptoms.
• Patient Interview [ Time Frame: Week 8-10 ]
  Qualitative telephone interviews with 16-20 patients of the mild whole-body hyperthermia group (Experimental group) to get detailed experiences of the patients (30-45 min).
• Adverse events (AE) [ Time Frame: Week 1-2 ]
  Description of adverse events during the interventions by therapists.
• Patient Diary [ Time Frame: Week 1-15 ]
  Documentation of pain progression, energy level, sleep, medication intake, number of steps, adverse events
• Pedometer (step count) [ Time Frame: Week 1-15 ]
  Individual activity profile

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: January 11, 2024)

• Blood count [ Time Frame: Week 0 ]
  (to measure baseline status)
• Blood count [ Time Frame: Week 2 ]
  (to measure acute effects)
• Blood count [ Time Frame: Week 3 ]
  (to measure acute effects)
• C-reactive Protein (CRP) [ Time Frame: Week 0 ]
  Level of C-reactive protein (CRP) in blood to measure inflammation
• C-reactive Protein (CRP) [ Time Frame: Week 2 ]
  Level of C-reactive protein (CRP) in blood to measure inflammation
• C-reactive Protein (CRP) [ Time Frame: Week 3 ]
  Level of C-reactive protein (CRP) in blood to measure inflammation
• Blood cell sedimenation rate (BSG) [ Time Frame: Week 0 ]
  to measure inflammation
• Blood cell sedimenation rate (BSG) [ Time Frame: Week 2 ]
  to measure inflammation
• Blood cell sedimenation rate (BSG) [ Time Frame: Week 3 ]
  to measure inflammation
• Cytokine panel [ Time Frame: Week 0 - baseline status ]
  Plasma levels of cytokines (TNF-a, IL-6, IL-8, IL-10, etc.)
• Cytokine panel [ Time Frame: Week 2 - before 3rd application of hyperthermia ]
  Plasma levels of cytokines (TNF-a, IL-6, IL-8, IL-10, etc.)
• Cytokine panel [ Time Frame: Week 3 - after last application of hyperthermia ]
  Plasma levels of cytokines (TNF-a, IL-6, IL-8, IL-10, etc.)
• post-Covid autoantibodies [ Time Frame: Week 0 - baseline status ]
  blood parameter
• post-Covid autoantibodies [ Time Frame: Week 2 - acute effects ]
  blood parameter
• post-Covid autoantibodies [ Time Frame: Week 3 - acute effects ]
  blood parameter
• Post-Covid pathogen reactivation [ Time Frame: Week 0 - baseline status ]
  pathogens EBV, CMV, VZV, Pan-/Corona; analysis by Elispot method
• Post-Covid pathogen reactivation [ Time Frame: Week 3 - acute effects ]
  pathogens EBV, CMV, VZV, Pan-/Corona; analysis by Elispot method
• Real time deformability cytometry (RT-DC) [ Time Frame: Week 0 - baseline status ]
  Blood cell characterization
• Real time deformability cytometry (RT-DC) [ Time Frame: Week 3 - acute effects ]
  Blood cell characterization

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Mild Water-filtered Infrared-A Whole-body Hyperthermia in Patients With Post-COVID Syndrome (HyPoCo)
• Official Title: Evaluation of the Efficacy of Mild Water-filtered Infrared-A Whole-body Hyperthermia to Improve Symptoms and Quality of Life in Patients With Post-COVID Syndrome (HyPoCo)
• Brief Summary: This study examines the efficacy of mild water-filtered whole-body hyperthermia during outpatient treatment in patients with post-COVID syndrome. The aim is to evaluate whether there can be an improvement in fatigue and quality of life. The duration of the study extends over a treatment period of approximately 2 weeks with two treatment units per week and a follow-up period of 3 months after the outpatient treatment.

Detailed Description

A total of about 60 participants over 18 years of age are sought, who will be divided into two groups of equal size after inclusion in the study. All participants will receive the same amount of water-filtered whole-body hyperthermia (WBH) under application of 10 L/min oxygen within the outpatient setting. One group receives the gentle form of WBH, the other group receives the classic, mild WBH, which differ in the intensity of the radiation. Gentle hyperthermia serves as a control group for mild hyperthermia.

All abnormalities are documented by the responsible therapists, doctors and nurses.

Blood parameters are collected before the start, after 2 applications and after the last application during the clinical stay. The aim here is to determine the differential blood count and inflammatory and immune parameters; among other things, autoantibody production is to be examined and monitored during the course of the study. In order to check the possible effectiveness of the treatment, various questionnaire values are also collected. The survey will take place at 3 points in time (at the beginning, after completion of the 4 treatments and 3 months afterwards).

In addition, a diary will be filled out in which patients will provide information on their sleep, personal energy level and pain level as well as their daily step count in order to create an activity profile. All patients receive a paper diary and a pedometer adapted to their individual characteristics in advance. The diary is to be kept from week 0 to week 15.

After completion of the study, qualitative interviews lasting around 30-45 minutes will be conducted with 16-20 participants in weeks 8-10 of the follow-up period. Participants are selected on the basis of socio-demographic and clinical characteristics with the aim of obtaining a sample that is as heterogeneous as possible. The interviews are conducted by telephone.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Treatment
• Condition: Post-COVID Syndrome

Intervention

• Other: mild hyperthermia group
  The hyperthermia treatment is carried out in a cycle of two treatments per week, with at least one day in between, over a period of two weeks, according to the manufacturer's instructions. For better tolerability, the application takes place under administration of 10L/min oxygen. According to the guidelines, the rectal (possibly vaginal) temperature (as body core temperature), heart rate and oxygen saturation (Sp02) are continuously determined during the hyperthermia treatment. During the treatment, continuous supervision by trained personnel is guaranteed, and a doctor is on call.
• Other: sham group
  Within the application, patients in the Sham group will undergo a hyperthermia application with virtually no overheating. To achieve this, the patients are positioned on the hyperthermia device in the same way as the intervention group. An insulating foil applied beforehand prevents direct irradiation with water-filtered infrared-A radiation. This prevents an increase in temperature. Due to the insulating blanket and the natural heat from the device and body, patients in the Sham group experience a gentle warmth that cannot be compared with regular whole-body hyperthermia and an increase in core body temperature of around 1.5°C. The number of treatments, the lighting conditions and procedures including 10L/min oxygen supply, is equal to the treatments in the intervention group.

Study Arms

• Experimental: mild hyperthermia group
  For the study, the method of passive whole-body hyperthermia is used. The IRATHERM®1000 system (Von Ardenne Institute for Applied Medical Research/Dresden) is used, in which the entire body is heated to a core body temperature above the physiological 37°C under the application of 10L/min oxygen. The aim is to achieve a core body temperature of 38.5°C within the framework of mild whole-body hyperthermia. After this warm-up phase, a temperature plateau phase of about 60 minutes follows, in which an attempt is made to maintain the core body temperature of 38.5°C. In the temperature plateau phase, a slight increase in the body core temperature is usually observed. The total time required for a session is given as 1.5 to 2 hours, but this depends on the individual constitution and daily condition of the patient and can be subject to fluctuations.
  Intervention: Other: mild hyperthermia group
• Sham Comparator: sham group
  Within the patient information, privacy policy, etc., there is talk of "gentle hyperthermia" and classic, "mild hyperthermia". This serves to introduce the sham intervention as a control group compared to the patient. Lighting conditions, procedures, instructions and explanations are indistinguishable. Within the application, patients of the sham group will receive a hyperthermia application almost without overheating. In order to achieve this, the patients will be positioned on the IRATHERM®1000 in accordance with the Von Ardenne Institute's regulations. Due to the insulating blanket and the natural device and body heat, the patients of the sham group experience a gentle warmth, which is not the same as regular whole-body hyperthermia and an increase in the body core temperature of about 1.5 °C. In the sham setting, the core body temperature increases by about 0.3 to 0.4 °C within a 55-minute session.
  Intervention: Other: sham group

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 11, 2024): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 31, 2025
• Estimated Primary Completion Date: December 31, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients aged between 18 and 75 years
• Confirmed diagnosis of post-COVID syndrome
• Fatigue: at least 51.5 points on the MFI-20 scale.
• Signed declaration of consent

Exclusion Criteria:

• Participation in other clinical studies
• Contraindications for hyperthermia (severe cardiovascular diseases with/above NYHA II, active tumor diseases, acute infections, hyperthyroidism (not adjusted), pregnant and breastfeeding women, epilepsy, high-grade cardiac arrhythmia including atrial fibrillation, multiple sclerosis, major skin lesions, photosensitivity disease, acute exacerbated bronchial asthma/COPD [Gold II to IV])
• Pleuritic chest pain
• Hyperthyroidism
• Poorly controlled diabetes mellitus
• Condition after critical illness due to COVID-19
• Patients with active tumor disease, with pneumological, rheumatic, endocrine or neurological concomitant diseases (including dementia, epilepsy, multiple sclerosis), in particular neurological diseases associated with cognitive or sensory disorders
• Severe liver or kidney diseases (liver cirrhosis, post liver transplant, autoimmune hepatitis, dialysis patients, post kidney transplant, acute kidney failure, autoimmune nephropathy)
• Patients with chronic cannabis use (exception: CBD for myalgia), long-term use of WHO class III opioids (e.g. for myalgia/joint pain), long-term use of immunosuppressive medication (steroids, biologics, MTX, leflunomide, azathioprine)
• Patients with psychiatric disorders (bipolar disorder, psychosis, schizophrenia, personality disorder)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Antje Fröhlich, M. Sc.; 004995150311650; antje.froehlich@sozialstiftung-bamberg.de

Contact: Özlem Öznur, M. Sc.; 004995150311650; oezlem.oeznur@sozialstiftung-bamberg.de

• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT06204458
• Other Study ID Numbers: 23050
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Jost Langhorst, Universität Duisburg-Essen
• Original Responsible Party: Same as current
• Current Study Sponsor: Universität Duisburg-Essen
• Original Study Sponsor: Same as current
• Collaborators: Bavarian State Ministry of Health and Care

Investigators

• Principal Investigator: Jost Langhorst, Prof. Dr.; Sozialstiftung Bamberg

• PRS Account: Universität Duisburg-Essen
• Verification Date: January 2024