Whole-body Hyperthermia for Moderate to Severe Depressive Disorder (HYPE2)

Whole-body Hyperthermia for Moderate to Severe Depressive Disorder - a Randomized Controlled Tiral

The primary aim of this study is to investigate the effectiveness of whole-body hyperthermia in addition to standard medical care in comparison to standard medical care alone on depressive symptom severity in patients with moderate to severe depressive disorder.

Secondary aims included further quality of life outcomes, immunological parameters, and tolerability/safety of the hyperthermia.

Study Overview

• Status: Completed
• Conditions: Depression, Unipolar
• Intervention / Treatment: Combination product: Whole-body hyperthermia + standard medical care; Combination product: Standard medical care

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Heidemarie Haller, PhD; Phone Number: +4920172377382; Email: heidemarie.haller@uk-essen.de
• Study Contact Backup: Name: Holger Cramer, PhD; Phone Number: +4920117425015; Email: holger.cramer@bosch-health-campus.com

Study Locations

• Germany
  • Essen, Germany, 45276
    • Department of Psychiatry, Psychotherapy and Addiciton Medicine, Evang. Kliniken Essen-Mitte

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Unipolar depression (diagnosed according to the DSM-IV)
• Moderate depression: 17-23 points on the HAMD-17 or severe depression: ≥24 points on the HAMD-17

Exclusion Criteria:

• Participants who did not respond to prior antidepressant drug treatment, electroconvulsive therapy, or sleep deprivation (therapy-resistant depression)
• Acute suicidality
• Prior treatment with whole-body hyperthermia
• Contraindications to hyperthermia treatment: acute or feverish infections, severe cardiovascular diseases (e.g. angina pectoris, heart failure, thrombosis, bleeding diathesis), severe gastrointestinal diseases (e.g. renal insufficiency, hepatitis, liver cirrhosis, peptic ulcer), severe neurological diseases (e.g. epilepsy, multiple sclerosis, cerebrovascular malformations or brain tumors), severe endocrine diseases (e.g. hyperthyroidism), or oncological diseases without remission
• Participants taking anti-inflammatory or immunosuppressive drugs
• Participants with severe psychiatric comorbidities (e.g. schizophrenia, schizoaffective disorder, bipolar disorder, dementia, ADHD, obsessive-compulsive disorder, PTSD, alcohol or drug addiction)
• Women during pregnancy and breastfeeding
• Lack of ability to consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Whole-body hyperthermia + standard medical care; Whole-body hyperthermia will be applied 2 times during 4 weeks in addition to guideline-based standard medical care for depression (anti-depressive drug treatment in combination with psychotherapy). At week 6, the primary outcome will be assessed. The participants will be reassessed 12 weeks after the start of the treatment with whole-body hyperthermia.	Combination product: Whole-body hyperthermia + standard medical care; Whole-body hyperthermia will be applied two times during 4 weeks (week 0 and 2 after randomization) in addition to standard medical care. The hyperthermia will be applied using Heckel-HT3000 MPIIb. During the 6 weeks of primary observation, the current medication should be maintained. The dose may be optimized with respect to clinical effectiveness and the reduction of side effects. The type of medication should not be changed during the 6 weeks. The use of additional somatic therapies such as sleep deprivation, light therapy, electroconvulsive therapy, or transcranial magnetic stimulation is not allowed.
Active Comparator: Standard medical care; Participants will maintain standard medical care for depression (anti-depressive drug treatment in combination with psychotherapy). At week 6, the primary outcome will be assessed. The participants will be reassessed 12 weeks after randomization.	Combination product: Standard medical care; Standard medical care included guideline-based anti-depressive drug treatment in combination with psychotherapy. During the 6 weeks of primary observation, the current medication should be maintained. The dose may be optimized with respect to clinical effectiveness and the reduction of side effects. The type of medication should not be changed during the 6 weeks. The use of additional somatic therapies such as sleep deprivation, light therapy, electroconvulsive therapy, or transcranial magnetic stimulation is not allowed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depression Severity: clinician-rated	Hamilton Rating Scale for Depression (HAMD-17)	week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depression Severity: clinician-rated	Hamilton Rating Scale for Depression (HAMD-17)	week 1
Depression Severity: clinician-rated	Hamilton Rating Scale for Depression (HAMD-17)	week 3
Depression Severity: clinician-rated	Hamilton Rating Scale for Depression (HAMD-17)	week 12
Depression Severity: patient-rated	Beck Depression Inventory II (BDI-II)	week 1
Depression Severity: patient-rated	Beck Depression Inventory II (BDI-II)	week 3
Depression Severity: patient-rated	Beck Depression Inventory II (BDI-II)	week 6
Depression Severity: patient-rated	Beck Depression Inventory II (BDI-II)	week 12
Global improvement: clinician-rated	Clinical Global Impression Scale (CGI)	week 1
Global improvement: clinician-rated	Clinical Global Impression Scale (CGI)	week 3
Global improvement: clinician-rated	Clinical Global Impression Scale (CGI)	week 6
Global improvement: clinician-rated	Clinical Global Impression Scale (CGI)	week 12
Global Functioning: clinician-rated	Global Assessment of Functioning Scale (GAF)	week 1
Global Functioning: clinician-rated	Global Assessment of Functioning Scale (GAF)	week 3
Global Functioning: clinician-rated	Global Assessment of Functioning Scale (GAF)	week 6
Global Functioning: clinician-rated	Global Assessment of Functioning Scale (GAF)	week 12
Fatigue: patient-rated	Multidimensional Fatigue Inventory (MFI)	week 1
Fatigue: patient-rated	Multidimensional Fatigue Inventory (MFI)	week 3
Fatigue: patient-rated	Multidimensional Fatigue Inventory (MFI)	week 6
Fatigue: patient-rated	Multidimensional Fatigue Inventory (MFI)	week 12
Stress: patient-rated	Perceived Stress-Scale (PSS)	week 1
Stress: patient-rated	Perceived Stress-Scale (PSS)	week 3
Stress: patient-rated	Perceived Stress-Scale (PSS)	week 6
Stress: patient-rated	Perceived Stress-Scale (PSS)	week 12
Quality of Life: patient-rated	Short Form Health Survey (SF-12)	week 1
Quality of Life: patient-rated	Short Form Health Survey (SF-12)	week 3
Quality of Life: patient-rated	Short Form Health Survey (SF-12)	week 6
Quality of Life: patient-rated	Short Form Health Survey (SF-12)	week 12
Biomarkers: interleukin 2	IL-2	week 1
Biomarkers: interleukin 2	IL-2	week 3
Biomarkers: interleukin 2	IL-2	week 6
Biomarkers: interleukin 2	IL-2	week 12
Biomarkers: interleukin 6	IL-6	week 1
Biomarkers: interleukin 6	IL-6	week 3
Biomarkers: interleukin 6	IL-6	week 6
Biomarkers: interleukin 6	IL-6	week 12
Biomarkers: interleukin 10	IL-10	week 1
Biomarkers: interleukin 10	IL-10	week 3
Biomarkers: interleukin 10	IL-10	week 6
Biomarkers: interleukin 10	IL-10	week 12
Biomarkers: tumor necrosis factor-alpha	TNF-alpha	week 1
Biomarkers: tumor necrosis factor-alpha	TNF-alpha	week 3
Biomarkers: tumor necrosis factor-alpha	TNF-alpha	week 6
Biomarkers: tumor necrosis factor-alpha	TNF-alpha	week 12
Biomarkers: high-sensitivity C-reactive Protein	hs-CRP	week 1
Biomarkers: high-sensitivity C-reactive Protein	hs-CRP	week 3
Biomarkers: high-sensitivity C-reactive Protein	hs-CRP	week 6
Biomarkers: high-sensitivity C-reactive Protein	hs-CRP	week 12
Biomarkers: soluble intercellular adhesion molecule-1	sICAM-1	week 1
Biomarkers: soluble intercellular adhesion molecule-1	sICAM-1	week 3
Biomarkers: soluble intercellular adhesion molecule-1	sICAM-1	week 6
Biomarkers: soluble intercellular adhesion molecule-1	sICAM-1	week 12
Biomarkers: tryptophan	tryptophan	week 1
Biomarkers: tryptophan	tryptophan	week 3
Biomarkers: tryptophan	tryptophan	week 6
Biomarkers: tryptophan	tryptophan	week 12
Biomarkers: kynurenine	kynurenine	week 1
Biomarkers: kynurenine	kynurenine	week 3
Biomarkers: kynurenine	kynurenine	week 6
Biomarkers: kynurenine	kynurenine	week 12
Biomarkers: neopterin	neopterin	week 1
Biomarkers: neopterin	neopterin	week 3
Biomarkers: neopterin	neopterin	week 6
Biomarkers: neopterin	neopterin	week 12
Adverse Events	Number of patients with adverse events, total number and type of adverse events	week 1
Adverse Events	Number of patients with adverse events, total number and type of adverse events	week 3
Adverse Events	Number of patients with adverse events, total number and type of adverse events	week 6
Adverse Events	Number of patients with adverse events, total number and type of adverse events	week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Expectations	Treatment Credibility Scale (TCS)	week -1

Collaborators and Investigators

• Sponsor: Universität Duisburg-Essen
• Investigators: Study Director: Gustav Dobos, Prof. MD, Center for Integrative Medicine and Health, University Hospital Essen, University of Duisburg-Essen

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Actual): January 20, 2023
• Study Completion (Actual): January 20, 2023

Study Registration Dates

• First Submitted: April 4, 2019
• First Submitted That Met QC Criteria: April 5, 2019
• First Posted (Actual): April 8, 2019

Study Record Updates

• Last Update Posted (Estimated): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Depression; Randomized Controlled Trial; Hyperthermia
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Wounds and Injuries; Body Temperature Changes; Heat Stress Disorders; Depression; Depressive Disorder; Hyperthermia; Fever
• Other Study ID Numbers: 18-8440-BO

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