HYPE2: Whole-body Hyperthermia for Moderate to Severe Depressive Disorder

Sponsor

Universität Duisburg-Essen (Other)

Overall Status

Recruiting

CT.gov ID

NCT03906149

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Depression, Unipolar	Combination Product: Whole-body hyperthermia + standard medical care Combination Product: Standard medical care	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

46 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 1, 2019

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Depression Severity: clinician-rated [week 6]
Hamilton Rating Scale for Depression (HAMD-17)

Secondary Outcome Measures

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

Other Outcome Measures

Treatment Expectations [week -1]
Treatment Credibility Scale (TCS)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Psychiatry, Psychotherapy and Addiciton Medicine, Kliniken Essen-Mitte	Essen		Germany	45276

Sponsors and Collaborators

Universität Duisburg-Essen

Investigators

Study Director: Gustav Dobos, Prof. MD, Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, Germany