Whole-body Hyperthermia for Moderate to Severe Depressive Disorder

Study Overview
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Brief Summary
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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.

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

Conditions
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Depression, Unipolar

Intervention / Treatment
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* Combination Product: Whole-body hyperthermia + standard medical care
* Combination Product: Standard medical care


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Whole-body hyperthermia + standard medical care<br>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<br>* 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.<br>|
| Active Comparator: Standard medical care<br>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<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Hyperthermia, Randomized Controlled Trial