Hyperthermia in Patients With Chronic Primary Pain - Effects on Thermoregulation, Somatosensory System and Movement Evoked Pain (HYPPRI-1)

Hyperthermia in Healthy and Patients With Chronic Primary Pain - Effects on Thermoregulation, Somatosensory System, Movement Evoked Pain (HYPPRI-1)

This study, in a quasi-experimental matched two-group pre-post design, investigates the effect of serial water-filtered whole-body hyperthermia on circadian core body temperature, the somatosensory system (nociception) and the movement evoked pain in healthy and patients with chronic primary pain (e.g., fibromyalgia). The intervention lasts 3 weeks with two treatment sessions per week.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy; Musculoskeletal Diseases; Rheumatic Diseases; Fibromyalgia; Hyperthermia; Body Temperature Changes; Circadian Rhythm; Neuromuscular Disease; Widespread Pain; Quantitative Sensory Testing; Muscular Disease; Somatosensory Function; Chronic Primary Pain
• Intervention / Treatment: Behavioral: serial whole body hyperthermia

Detailed Description

A total of 30 healthy participants and 30 participants with chronic primary pain between the ages of 18 and 70 are being sought. All participants will receive the same amount of water-filtered whole-body hyperthermia in outpatient or semi-inpatient treatment. All abnormalities and side effects will be documented by the responsible therapists and doctors. Changes in circadian core body temperature, sensory or nociceptive sensitivities of the somatosensory system, and movement-evoked pain will be recorded, and blood parameters for nociceptive plasticity will be collected. For secondary efficacy, specific questionnaires on pain experience, fatigue, depression, and fear avoidance behavior will be collected 7 and 25 weeks after therapy.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kay-Uwe Hanusch, Dr.scient.med; Phone Number: +41 31 848 5005; Email: kay.hanusch@bfh.ch

Study Locations

• Switzerland
  • Canton of Bern
    • Bern, Canton of Bern, Switzerland, 3012
      • Bern University of Applied Science
      • Contact: Kay-Uwe Hanusch, Dr.scient.med; Phone Number: +41 31 848 5005; Email: kay.hanusch@bfh.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

patients:

• Confirmed diagnosis of widespread pain (ICD-11 MG30.01)
• Widespread Pain Index (WPI) ≥ 7 and Symptom Severity (SS) scale ≥ 5 or WPI) ≥ 3 and SS ≥ 9,
• Pain >= 3 month and VAS >= 4,0
• Body - infrared-A-Bulb Distance < 38cm (overweight participants)
• Signed declaration of consent

healthy:

• No chronic illnesses
• No acute infections
• No regular medication: To avoid interactions
• BMI ≤ 40kg/cm2
• Mental health: No psychiatric diagnoses or psychotropic medication in your medical history

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
• Participants with severe somatic, rheumatic concomitant endocrine or neurological diseases, in particular neurological diseases associated with cognitive disorders, severe liver or kidney and cardiac diseases
• participants 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
• participants with pain due to a serious psychiatric illness (bipolar disorder, psychosis, personality disorder, severe depression, substance abuse) and serious systemic or neurological disorders
• pregnancy or breastfeeding (for women)
• Intake of medication within 6 weeks that inhibits the reuptake of the neurotransmitter serotonin or binds to receptors of this neurotransmitter group

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: serial whole body hyperthermia; For the study, the method of water-filtered whole-body hyperthermia is used. The HT 3000 system (by heckel medizintechnik GmbH, Olgastrasse 25, 73728 Esslingen, Garmany) 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 15 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 2.5 to 3 hours, but this depends on the individual constitution and daily condition of the patient and can be subject to fluctuations.

Behavioral: serial whole body hyperthermia; 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 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 hyperthermiatreatment. During the treatment, continuous supervision by trained personnel is guaranteed, and a doctor is on call.; Other Names: passive whole body hyperthermia; water filtered whole body hyperthermia; moderate whole body infrared-A hyperthermia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Circadian core body temperature	A BodyCap HF (high-frequency) measurement capsule is used for circadian monitoring of core body temperature over a 24-hour period. The single-use capsule is swallowed and excreted naturally after the measurement.	Week 0
Circadian core body temperature	A BodyCap HF (high-frequency) measurement capsule is used for circadian monitoring of core body temperature over a 24-hour period. The single-use capsule is swallowed and excreted naturally after the measurement.	Week 5
Cold detection threshold (CDT); °C	CDT is a part of quantitative sensory testing. A psychophysical testing method in which calibrated cold temperature stimuli (Thermode) 3x applied to the skin. Z-values are calculate.	Week 0
Cold detection threshold (CDT); °C	CDT is a part of quantitative sensory testing. A psychophysical testing method in which calibrated cold temperature stimuli (Thermode) 3x applied to the skin. Z-values are calculate.	week 5
Warm detection threshold (WDT); °C	WDT is a part of quantitative sensory testing. A psychophysical testing method in which calibrated warm temperature stimuli (Thermode) 3x applied to the skin. Z-values are calculate.	Week 0
Warm detection threshold (WDT); °C	WDT is a part of quantitative sensory testing. A psychophysical testing method in which calibrated warm temperature stimuli (Thermode) 3x applied to the skin. Z-values are calculate.	week 5
Thermal sensory limen (TSL) ; °C	TSL is a part of quantitative sensory testing. A psychophysical testing method in which calibrated warm and cold temperature stimuli (Thermode) alternately 6x applied to the skin. Z-values are calculate and count number of cold stimuli that are perceived as hot.	week 0
Thermal sensory limen (TSL) ; °C	TSL is a part of quantitative sensory testing. A psychophysical testing method in which calibrated warm and cold temperature stimuli (Thermode) alternately 6x applied to the skin. Z-values are calculate and count number of cold stimuli that are perceived as hot.	week 5
Cold pain threshold (CPT); °C	CPT is a part of quantitative sensory testing. A psychophysical testing method in which calibrated nociceptive cold temperature stimuli (Thermode) 3x applied to the skin. Z-values are calculate.	week 0
Cold pain threshold (CPT); °C	CPT is a part of quantitative sensory testing. A psychophysical testing method in which calibrated nociceptive cold temperature stimuli (Thermode) 3x applied to the skin. Z-values are calculate.	week 5
Heat pain threshold (HPT); °C	HPT is a part of quantitative sensory testing. A psychophysical testing method in which calibrated nociceptive heat temperature stimuli (Thermode) 3x applied to the skin. Z-values are calculate.	week 0
Heat pain threshold (HPT); °C	HPT is a part of quantitative sensory testing. A psychophysical testing method in which calibrated nociceptive heat temperature stimuli (Thermode) 3x applied to the skin. Z-values are calculate.	week 5
Mechanical detection threshold (MDT) ; mN	MDT is a part of quantitative sensory testing. A psychophysical testing method in which calibrated mechanical stimuli (different strengths Frey filaments) 10x applied to the skin Z-values are calculated.	week 0
Mechanical detection threshold (MDT) ; mN	MDT is a part of quantitative sensory testing. A psychophysical testing method in which calibrated mechanical stimuli (different strengths Frey filaments) 10x applied to the skin Z-values are calculated.	week 5
Mechanical pain threshold (MPT), count of sharp and blunt stimuli	MPT is a part of quantitative sensory testing. A psychophysical testing method in which calibrated mechanical stimuli (PinPrick with different weights) 10x applied to the skin. Mechanical pain threshold (MPT). Count number of sharp and blunt stimuli. Z-values are calculated.	week 0
Mechanical pain threshold (MPT), count of sharp and blunt stimuli	MPT is a part of quantitative sensory testing. A psychophysical testing method in which calibrated mechanical stimuli (PinPrick with different weights) 10x applied to the skin. Mechanical pain threshold (MPT). Count number of sharp and blunt stimuli. Z-values are calculated.	week 5
Mechanical pain sensitivity (MPS) ; NRS	MPS is a part of quantitative sensory testing. A psychophysical testing method in which calibrated mechanical stimuli (PinPrick with different weights) 35x applied to the skin. The Numeric Rating Scale (0 = no pain to 100 = worst pain imaginable) is queried. Z-values are calculated.	week 0
Mechanical pain sensitivity (MPS) ; NRS	MPS is a part of quantitative sensory testing. A psychophysical testing method in which calibrated mechanical stimuli (PinPrick with different weights) 35x applied to the skin. The Numeric Rating Scale (0 = no pain to 100 = worst pain imaginable) is queried. Z-values are calculated.	week 5
Summative pain amplification (WUR); NRS	WUR (wind-up ratio) is a part of quantitative sensory testing. A psychophysical testing method in which calibrated mechanical stimuli (PinPrick with different weights) single and seriell 10x applied to the skin. The Numeric Rating Scale (0 = no pain to 100 = worst pain imaginable) for single and seriell stimuli are compared into relation. Z-values are calculated.	week 0
Summative pain amplification (WUR); NRS	WUR (wind-up ratio) is a part of quantitative sensory testing. A psychophysical testing method in which calibrated mechanical stimuli (PinPrick with different weights) single and seriell 10x applied to the skin. The Numeric Rating Scale (0 = no pain to 100 = worst pain imaginable) for single and seriell stimuli are compared into relation. Z-values are calculated.	week 5
Vibration detection threshold (VDT) ; x/8	VDT is a part of quantitative sensory testing. A psychophysical testing method in which calibrated mechanical stimuli (64Hz tuning fork) 3x applied to the skin. The x/8 vibration is measure (0/8 no perception and 8/8 strengthest perception). Z-values are calculated.	week 0
Vibration detection threshold (VDT) ; x/8	VDT is a part of quantitative sensory testing. A psychophysical testing method in which calibrated mechanical stimuli (64Hz tuning fork) 3x applied to the skin. The x/8 vibration is measure (0/8 no perception and 8/8 strengthest perception). Z-values are calculated.	week 5
Pressure pain threshold (PPT), kgf/1cm2	PPT is a part of quantitative sensory testing. A psychophysical testing method in which calibrated mechanical stimuli (pain pressure algometer) 5x applied to the skin. Z-values are calculated.	week 0
Pressure pain threshold (PPT), kgf/1cm2	PPT is a part of quantitative sensory testing. A psychophysical testing method in which calibrated mechanical stimuli (pain pressure algometer) 5x applied to the skin. Z-values are calculated.	week 5
Dynamic mechanical allodynia (DMA), NRS	DMA is a part of quantitative sensory testing. A psychophysical testing method in which calibrated mechanical stimuli (brush, cotton wool and Q-Tip) 5x applied to the skin. Z-values are calculated. The Numeric Rating Scale (0 = no pain to 100 = worst pain imaginable) ist queried. Z-values are calculated.	week 0
Dynamic mechanical allodynia (DMA), NRS	DMA is a part of quantitative sensory testing. A psychophysical testing method in which calibrated mechanical stimuli (brush, cotton wool and Q-Tip) 5x applied to the skin. Z-values are calculated. The Numeric Rating Scale (0 = no pain to 100 = worst pain imaginable) ist queried. Z-values are calculated.	week 5
6-Minute Walk Test (6MWT)	Walking back and forth as far as possible along a 30-meter corridor in 6 minutes, taking breaks as needed ( total distance covered is recorded in meters, pain is measured before and after the test, 0 = no pain, 10 = worst pain imaginable)	Week 0
6-Minute Walk Test (6MWT)	Walking back and forth as far as possible along a 30-meter corridor in 6 minutes, taking breaks as needed ( total distance covered is recorded in meters, pain is measured before and after the test, 0 = no pain, 10 = worst pain imaginable)	Week 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
McGill Pain Questionnaire (MPQ)	The instrument assesses subjective pain experience and evaluates both the quality and numerical intensity of pain (0 = no pain; 10 = worst pain imaginable)	Week 0
McGill Pain Questionnaire (MPQ)	The instrument assesses subjective pain experience and evaluates both the quality and numerical intensity of pain (0 = no pain; 10 = worst pain imaginable)	Week 5
McGill Pain Questionnaire (MPQ)	The instrument assesses subjective pain experience and evaluates both the quality and numerical intensity of pain (0 = no pain; 10 = worst pain imaginable)	Week 12
McGill Pain Questionnaire (MPQ)	The instrument assesses subjective pain experience and evaluates both the quality and numerical intensity of pain (0 = no pain; 10 = worst pain imaginable)	Week 30
Multidimensional 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
Multidimensional 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 5
Multidimensional 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
Multidimensional 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
General Depression Scale (ADS-L)	is a german self-report questionnaire designed to assess depressive symptoms in the general population adapted from the CES-D. (20 items, 4-point Likert scale (0 = rarely or none of the time, 3 = most or all of the time)	Week 0
General Depression Scale (ADS-L)	is a german self-report questionnaire designed to assess depressive symptoms in the general population adapted from the CES-D. (20 items, 4-point Likert scale (0 = rarely or none of the time, 3 = most or all of the time)	Week 5
General Depression Scale (ADS-L)	is a german self-report questionnaire designed to assess depressive symptoms in the general population adapted from the CES-D. (20 items, 4-point Likert scale (0 = rarely or none of the time, 3 = most or all of the time)	Week 12
General Depression Scale (ADS-L)	is a german self-report questionnaire designed to assess depressive symptoms in the general population adapted from the CES-D. (20 items, 4-point Likert scale (0 = rarely or none of the time, 3 = most or all of the time)	Week 30
Fear Avoidance Beliefs Questionnaire (FABQ)	Is a psychological questionnaire designed to assess a person's beliefs about how physical activity and work may influence their pain. It focuses on fear-avoidance behaviours, particularly in individuals with musculoskeletal pain (e.g., low back pain). The questionnaire consists of 16 items divided into two subscales: physical activity (FABQ-PA) and work (FABQ-W). Items are rated on a 7-point Likert scale (from "completely disagree" to "completely agree").	Week 0
Fear Avoidance Beliefs Questionnaire (FABQ)	Is a psychological questionnaire designed to assess a person's beliefs about how physical activity and work may influence their pain. It focuses on fear-avoidance behaviours, particularly in individuals with musculoskeletal pain (e.g., low back pain). The questionnaire consists of 16 items divided into two subscales: physical activity (FABQ-PA) and work (FABQ-W). Items are rated on a 7-point Likert scale (from "completely disagree" to "completely agree").	Week 5
Fear Avoidance Beliefs Questionnaire (FABQ)	Is a psychological questionnaire designed to assess a person's beliefs about how physical activity and work may influence their pain. It focuses on fear-avoidance behaviours, particularly in individuals with musculoskeletal pain (e.g., low back pain). The questionnaire consists of 16 items divided into two subscales: physical activity (FABQ-PA) and work (FABQ-W). Items are rated on a 7-point Likert scale (from "completely disagree" to "completely agree").	Week 12
Fear Avoidance Beliefs Questionnaire (FABQ)	Is a psychological questionnaire designed to assess a person's beliefs about how physical activity and work may influence their pain. It focuses on fear-avoidance behaviours, particularly in individuals with musculoskeletal pain (e.g., low back pain). The questionnaire consists of 16 items divided into two subscales: physical activity (FABQ-PA) and work (FABQ-W). Items are rated on a 7-point Likert scale (from "completely disagree" to "completely agree").	Week 30
Avoidance-Endurance Fast-Screen (AEFS)	Description: Is a short screening questionnaire designed to identify maladaptive pain coping patterns, specifically avoidance and endurance behaviours in individuals with musculoskeletal pain. It differentiates between fear-avoidance responses and endurance-related coping styles (e.g., persistence despite pain). The AEFS includes a 7-point scale (0=never to 6=always) for Pain Persistence (PPS) from the Avoidance-Endurance Questionnaire (AEQ), as well as two dichotomous (0=yes, 1=no) mood items from the Beck-Depressions-Inventar. The PPS scale is administered using two response scales for coping with mild and severe pain.	week 0
Avoidance-Endurance Fast-Screen (AEFS)	Description: Is a short screening questionnaire designed to identify maladaptive pain coping patterns, specifically avoidance and endurance behaviours in individuals with musculoskeletal pain. It differentiates between fear-avoidance responses and endurance-related coping styles (e.g., persistence despite pain). The AEFS includes a 7-point scale (0=never to 6=always) for Pain Persistence (PPS) from the Avoidance-Endurance Questionnaire (AEQ), as well as two dichotomous (0=yes, 1=no) mood items from the Beck-Depressions-Inventar. The PPS scale is administered using two response scales for coping with mild and severe pain.	week 5
Avoidance-Endurance Fast-Screen (AEFS)	Description: Is a short screening questionnaire designed to identify maladaptive pain coping patterns, specifically avoidance and endurance behaviours in individuals with musculoskeletal pain. It differentiates between fear-avoidance responses and endurance-related coping styles (e.g., persistence despite pain). The AEFS includes a 7-point scale (0=never to 6=always) for Pain Persistence (PPS) from the Avoidance-Endurance Questionnaire (AEQ), as well as two dichotomous (0=yes, 1=no) mood items from the Beck-Depressions-Inventar. The PPS scale is administered using two response scales for coping with mild and severe pain.	week 12
Avoidance-Endurance Fast-Screen (AEFS)	Description: Is a short screening questionnaire designed to identify maladaptive pain coping patterns, specifically avoidance and endurance behaviours in individuals with musculoskeletal pain. It differentiates between fear-avoidance responses and endurance-related coping styles (e.g., persistence despite pain). The AEFS includes a 7-point scale (0=never to 6=always) for Pain Persistence (PPS) from the Avoidance-Endurance Questionnaire (AEQ), as well as two dichotomous (0=yes, 1=no) mood items from the Beck-Depressions-Inventar. The PPS scale is administered using two response scales for coping with mild and severe pain.	week 30

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
BDNF	Brain-Derived Neurotrophic Factor (BDNF) in blood to measure nociplasticity	Week 0
BDNF	Brain-Derived Neurotrophic Factor (BDNF) in blood to measure nociplasticity	Week 5
PRISE (Patient-Rated Inventory of Side Effects)	A tool used to assess the presence and severity of side effects (0=no severity, 3= greater severity) across nine organ/function domains, including gastrointestinal, nervous system, heart, eyes/ears, skin, genital/urinary, sleep, sexual function, and other areas	30min post treatment

Collaborators and Investigators

• Sponsor: Bern University of Applied Sciences
• Collaborators: Dr. med. h.c Erwin Braun Stiftung
• Investigators: Study Director: Kay-Uwe Hanusch, Dr.scient.med, Bern University of Applied Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 30, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: July 8, 2025
• First Submitted That Met QC Criteria: July 28, 2025
• First Posted (Actual): August 3, 2025

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: hyperthermia; healthy; quantitative sensory testing; widespread pain; chronic primary pain; circadian body temperature
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Wounds and Injuries; Connective Tissue Diseases; Heat Stress Disorders; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Signs and Symptoms; Hyperthermia; Fibromyalgia; Chronic Pain; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Rheumatic Diseases; Body Temperature Changes
• Other Study ID Numbers: F.016677-42-PHYW-1

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