Hyperthermia in Fibromyalgia Syndrome (HYPAIN)

A Randomised Sham-controlled Study on the Effectiveness of Mild Water-filtered Infrared-A Whole-body Hyperthermia in Improving Symptoms and Quality of Life in Patients With Fibromyalgia Syndrome

This study will examine the effectiveness of water-filtered whole-body hyperthermia during an outpatient setting in patients with fibromyalgia.

The duration of the study is about 3 weeks with two treatment units per week and a passive period (follow-up measurement) of 24 weeks after the outpatient setting.

Study Overview

• Status: Completed
• Conditions: Fibromyalgia
• Intervention / Treatment: Behavioral: Hyperthermia Group; Behavioral: Sham-Group

Detailed Description

A total of about 40 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 within the outpatient setting. One group receives the gentle form of GKHT, the other group receives the classic, mild GHKT. All abnormalities are documented by the responsible therapists, doctors and nurses. Changes in the area of pain and functional limitations as well as the intake of required medication are also recorded.

Before the start and after the completion of the studies, within the clinical stay, blood parameters were collected. In order to determine the secondary effectiveness of different questionnaire values are also collected. These are also documented after week 12 and after week 24, by means of telephone enquiries.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Bayern
    • Bamberg, Bayern, Germany, 96049
      • Sozialstiftung Bamberg, Klinik für Intergrative Medizin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• confirmed diagnosis of fibromyalgia (FSQ)
• Pain VAS >= 4,0
• Signed declaration of consent

Exclusion Criteria:

• Participation in other clinical studies
• Contraindications for hyperthermia (severe cardiovascular diseases, tumour diseases, acute infections, pregnant and breastfeeding women)
• Acute and / or feverish microbial infections
• Patients with severe somatic, rheumatic concomitant endocrine or neurological diseases, in particular neurological diseases associated with cognitive disorders, severe liver or kidney and cardiac diseases
• Patients who are permanently treated with opioids, cannabis, immunosuppressive drugs (e.g. corticoids, immunosuppressants) or alpha/beta-A(nta)gonists due to a disease from the group described above
• Patients with pain due to a serious psychiatric illness (bipolar disorder, psychosis, personality disorder, severe depression, substance abuse) and serious systemic or neurological disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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. 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.	Behavioral: Hyperthermia Group; The first hyperthermia treatment of the series is carried out for the second aptitude test, directly following the randomisation in the intervention group at the Hospital for Naturopathy and Integrative Medicine in Bamberg. The hyperthermia treatment is then carried out in a cycle of two treatments per week, with at least one day in between, over a period of three weeks, according to the manufacturer's instructions. 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.
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.	Behavioral: Sham-Group; The number of treatments is equal to the number of treatments in the intervention group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brief Pain Inventory (BPI) - Intensity of pain (Numeric Rating Scale, NRS)	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.	Week 0
Brief Pain Inventory (BPI) - Intensity of pain (Numeric Rating Scale, NRS)	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.	Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multidimensionl Fatigue Inventory (MFI-20)	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).	Week 0
Multidimensionl Fatigue Inventory (MFI-20)	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).	Week 4
Multidimensionl Fatigue Inventory (MFI-20)	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).	Week 12
Multidimensionl Fatigue Inventory (MFI-20)	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).	Week 30
Pittsburgh Sleep quality index (PSQI)	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.	Week 0
Pittsburgh Sleep quality index (PSQI)	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.	Week 4
Pittsburgh Sleep quality index (PSQI)	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.	Week 12
Pittsburgh Sleep quality index (PSQI)	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.	Week 30
Fibromyalgia Impact Questionnaire (FIQ)	An inventory measuring the disease-specific quality of life including 10 questions. The first question covers physical functioning ranging from 0 (always) to 3 (never). The second question is about wellbeing and the third examines the ability to work. Question 4-10 examine restrictions with visual analog scales (e.g. 0mm = not tired; 100mm = very tired) covering various symptoms like fatigue, anxiety or depression.	Week 0
Fibromyalgia Impact Questionnaire (FIQ)	An inventory measuring the disease-specific quality of life including 10 questions. The first question covers physical functioning ranging from 0 (always) to 3 (never). The second question is about wellbeing and the third examines the ability to work. Question 4-10 examine restrictions with visual analog scales (e.g. 0mm = not tired; 100mm = very tired) covering various symptoms like fatigue, anxiety or depression.	Week 4
Fibromyalgia Impact Questionnaire (FIQ)	An inventory measuring the disease-specific quality of life including 10 questions. The first question covers physical functioning ranging from 0 (always) to 3 (never). The second question is about wellbeing and the third examines the ability to work. Question 4-10 examine restrictions with visual analog scales (e.g. 0mm = not tired; 100mm = very tired) covering various symptoms like fatigue, anxiety or depression.	Week 12
Fibromyalgia Impact Questionnaire (FIQ)	An inventory measuring the disease-specific quality of life including 10 questions. The first question covers physical functioning ranging from 0 (always) to 3 (never). The second question is about wellbeing and the third examines the ability to work. Question 4-10 examine restrictions with visual analog scales (e.g. 0mm = not tired; 100mm = very tired) covering various symptoms like fatigue, anxiety or depression.	Week 30
Patient Global Impression of Change	One question about the patients global impression of change due to the therapy ranging from 1 (very much improved) to 7 (very much worse).	Week 4
Patient Global Impression of Change	One question about the patients global impression of change due to the therapy ranging from 1 (very much improved) to 7 (very much worse).	Week 12
Patient Global Impression of Change	One question about the patients global impression of change due to the therapy ranging from 1 (very much improved) to 7 (very much worse).	Week 30
Pain Diary	Pain diary measuring the daily pain level at baseline. It also includes medication intakes, accompanying treatments and space for additional comments.	Week -2-0
Pain Diary	Pain diary measuring the daily pain level during the period of intervention. It also includes medication intakes, accompanying treatments and space for additional comments.	Week 1-3
Additional Treatments/Change of Medication	Record of additional treatments/change of medication to control for effects.	Week 12
Additional Treatments/Change of Medication	Record of additional treatments/change of medication to control for effects.	Week 30
Short-Form Mc Gill Pain Questionnaire - Deutsche Version (SF-MPQ-D)	The pain inventory includes three questions. The first one examines the quality of the pain with 15 items e.g. "throbbing", "shooting" raning from 0 (None) to 3 (severe). The second question examines the current level of pain with a visal analog scale (0mm= No Pain, 100mm= worst possible pain"). The third one examines the intensitiy of the whole pain experience (0=no Pain, 5 = excruciating).	Week 0
Short-Form Mc Gill Pain Questionnaire - Deutsche Version (SF-MPQ-D)	The pain inventory includes three questions. The first one examines the quality of the pain with 15 items e.g. "throbbing", "shooting" raning from 0 (None) to 3 (severe). The second question examines the current level of pain with a visal analog scale (0mm= No Pain, 100mm= worst possible pain"). The third one examines the intensitiy of the whole pain experinece (0=no Pain, 5 = excruciating).	Week 4
Short-Form Mc Gill Pain Questionnaire - Deutsche Version (SF-MPQ-D)	The pain inventory includes three questions. The first one examines the quality of the pain with 15 items e.g. "throbbing", "shooting" raning from 0 (None) to 3 (severe). The second question examines the current level of pain with a visal analog scale (0mm= No Pain, 100mm= worst possible pain"). The third one examines the intensitiy of the whole pain experience (0=no Pain, 5 = excruciating).	Week 12
Short-Form Mc Gill Pain Questionnaire - Deutsche Version (SF-MPQ-D)	The pain inventory includes three questions. The first one examines the quality of the pain with 15 items e.g. "throbbing", "shooting" raning from 0 (None) to 3 (severe). The second question examines the current level of pain with a visal analog scale (0mm= No Pain, 100mm= worst possible pain"). The third one examines the intensitiy of the whole pain experience (0=no Pain, 5 = excruciating).	Week 30
age	age in years	Week 0
sex	identification of gender	Week 0
height	in meters	Week 0
weight	in kg	Week 0
marital status	identification of marital status	Week 0
education	identification of the educational level	Week 0
job	identification of the current job (4 questions about job/application for pension)	Week 0
G-EEE (Generic Rating for Treatment pre-experiences, Treatment Expectations and Treatment effects)	A non validated inventory including 11 items measuring pre-experiences, treatment expectations and treatment effects.	Week 0
G-EEE (Generic Rating for Treatment pre-experiences, Treatment Expectations and Treatment effects)	A non validated inventory including 11 items measuring pre-experiences, treatment expectations and treatment effects.	Week 4
G-EEE (Generic Rating for Treatment pre-experiences, Treatment Expectations and Treatment effects)	A non validated inventory including 11 items measuring pre-experiences, treatment expectations and treatment effects.	Week 12
G-EEE (Generic Rating for Treatment pre-experiences, Treatment Expectations and Treatment effects)	A non validated inventory including 11 items measuring pre-experiences, treatment expectations and treatment effects.	Week 30
SF-36 health survey	An inventory including 36 item measuring the current health status and generic quality of life of the patients. It includes eight subscales, that can be summarized in one physical and one psychological summary scale.	Week 0
SF-36 health survey	An inventory including 36 item measuring the current health status and generic quality of life of the patients. It includes eight subscales, that can be summarized in one physical and one psychological summary scale.	Week 4
SF-36 health survey	An inventory including 36 item measuring the current health status and generic quality of life of the patients. It includes eight subscales, that can be summarized in one physical and one psychological summary scale.	Week 12
SF-36 health survey	An inventory including 36 item measuring the current health status and generic quality of life of the patients. It includes eight subscales, that can be summarized in one physical and one psychological summary scale.	Week 30
Shortform of PHQ-D (Patient Health Questionnaire)	An inventory measurung the psychological health status including among others 9 items about depression (PHQ-9), 15 items about somatization (PHQ-15) and 7 items about general anxietey (GAD-7).	Week 0
Shortform of PHQ-D (Patient Health Questionnaire)	An inventory measurung the psychological health status including among others 9 items about depression (PHQ-9), 15 items about somatization (PHQ-15) and 7 items about general anxietey (GAD-7).	Week 4
Shortform of PHQ-D (Patient Health Questionnaire)	An inventory measurung the psychological health status including among others 9 items about depression (PHQ-9), 15 items about somatization (PHQ-15) and 7 items about general anxietey (GAD-7).	Week 12
Shortform of PHQ-D (Patient Health Questionnaire)	An inventory measurung the psychological health status including among others 9 items about depression (PHQ-9), 15 items about somatization (PHQ-15) and 7 items about general anxietey (GAD-7).	Week 30
Brief Pain Inventory (BPI) - Intensity of pain (Numeric Rating Scale, NRS)	An inventory including 15 Items about the intensity of pain (4 items, numeric rating scales from 1 (no pain) to 10 (worst pain imaginable), pain impairment (7 items with NRS from 1-10) and the efficacy of medications/treatments.	Week 12
Brief Pain Inventory (BPI) - Intensity of pain (Numeric Rating Scale, NRS)	An inventory including 15 Items about the intensity of pain (4 items, numeric rating scales from 1 (no pain) to 10 (worst pain imaginable), pain impairment (7 items with NRS from 1-10) and the efficacy of medications/treatments.	Week 30
Patient Interview	Qualitative telephone interviews with 10 patients of the mild whole body hyperthermia group (Experimental group) to get detailed experiences of the patients (30-45 min).	Week 12
Adverse events (AE)	Description of adverse events during the interventions by therapists.	Week 1-3

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood count	(to measure baseline status)	Week 0
Blood count	(to measure acute effects)	Week 3 - after last intervention
Blood count	(to measure acute effects)	Week 4
C-reactive Protein (CRP)	Level of c-reactive protein (CRP) in blood to measure inflammation.	Week 0
C-reactive Protein (CRP)	Level of c-reactive protein (CRP) in blood to measure inflammation (to measure acute effects).	Week 3 - after last intervention
C-reactive Protein (CRP)	Level of c-reactive protein (CRP) in blood to measure inflammation.	Week 4
Blood cell sedimenation rate (BSG)	Serum parameter.	Week 0
Blood cell sedimenation rate (BSG)	Serum parameter (to measure acute effects).	Week 3 - after last intervention
Blood cell sedimenation rate (BSG)	Serum parameter.	Week 4
Coagulation	Coagulation measured in blood.	Week 0
Coagulation	Coagulation measured in blood.	Week 3 - after last intervention
Coagulation	Coagulation measured in blood.	Week 4
Tumor Necrosis Factor (TNF-α)	Serum parameter.	Week 0
Tumor Necrosis Factor (TNF-α)	Serum parameter.	Week 3 - after last intervention
Tumor Necrosis Factor (TNF-α)	Serum parameter.	Week 4
Interleukin-1 (IL-1)	Serum parameter (Zytokines).	Week 0
Interleukin-1 (IL-1)	Serum parameter (Zytokines).	Week 3 - after last intervention
Interleukin-1 (IL-1)	Serum parameter (Zytokines).	Week 4
Interleukin-6 (IL-6)	Serum parameter (Zytokines).	Week 0
Interleukin-6 (IL-6)	Serum parameter (Zytokines).	Week 3 - after last intervention
Interleukin-6 (IL-6)	Serum parameter (Zytokines).	Week 4
Interleukin-8 (IL-8)	Serum parameter (Zytokines).	Week 0
Interleukin-8 (IL-8)	Serum parameter (Zytokines).	Week 3 - after last intervention
Interleukin-8 (IL-8)	Serum parameter (Zytokines).	Week 4
Interleukin-10 (IL-10)	Serum parameter (Zytokines).	Week 0
Interleukin-10 (IL-10)	Serum parameter (Zytokines).	Week 3 - after last intervention
Interleukin-10 (IL-10)	Serum parameter (Zytokines).	Week 4
creatinine	Serum parameter.	Week 4
GOT, GPT, GGT	Serum Parameters - Liver enzymes.	Week 4

Collaborators and Investigators

• Sponsor: Jost Langhorst
• Investigators: Study Director: Jost Langhorst, Prof., Sozialstiftung Bamberg

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2020
• Primary Completion (Actual): April 19, 2021
• Study Completion (Actual): December 13, 2021

Study Registration Dates

• First Submitted: April 13, 2021
• First Submitted That Met QC Criteria: November 15, 2021
• First Posted (Actual): November 26, 2021

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: pain; hyperthermia; fibromyalgia syndrome
• Additional Relevant MeSH Terms: Nervous System Diseases; Wounds and Injuries; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Body Temperature Changes; Heat Stress Disorders; Fibromyalgia; Myofascial Pain Syndromes; Hyperthermia; Fever
• Other Study ID Numbers: 20079

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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