Depression, Major Depressive Disorder
Conditions
Keywords
hyperthermia, heat therapy, passive heating
Brief summary
This randomized two-arm intervention trial administers 8 weekly cognitive behavioral therapy (CBT) sessions and 4 bi-weekly active whole-body hyperthermia (active WBH) sessions or 4 bi-weekly sham WBH sessions to adults aged 18 years or older with major depressive disorder (MDD).
Detailed description
Major Depressive Disorder afflicts more than 300 million people worldwide and is the leading cause of life years lost to disability. Current treatments have important limitations in efficacy and, in the case of medication, substantial side-effects. There is thus a compelling need for additional effective, well-tolerated treatments. One such potential treatment is whole-body hyperthermia (WBH). The investigators hypothesize that active WBH may be particularly effective in combination with cognitive behavioral therapy (CBT), an established treatment for depression. This randomized two-arm trial will pilot and optimize procedures for randomizing participants to receive CBT (8 weekly sessions) and 4 bi-weekly whole-body hyperthermia (active WBH) or 4 bi-weekly sham WBH sessions. This work holds important promise to improve treatment of depression and advance understanding of the role of integrated mind-body therapies for mood disorders.
Interventions
BEHAVIORALCognitive Behavioral Therapy (CBT)
Cognitive Behavioral Therapy (CBT) is a behavioral (psychotherapeutic) intervention for major depressive disorder (MDD). A highly trained masters' or PhD-level clinician will administer 8 weekly CBT sessions (\~50 minutes each), following the standard cognitive behavioral therapy for depression protocol.
DEVICEActive Whole-Body Hyperthermia (Active WBH)
Active whole-body hyperthermia (active WBH) will be administered by trained research assistants. Preparation for the active WBH session, the active WBH session, and cool down will last 3.5 hours, with heating lasting approximately 90-100 minutes (and no longer than 140 minutes). The treatment will take place in an infrared sauna dome, and the active heating phase will last until the participants has achieved a core (rectal) temperature of 38.5 C.
DEVICESham Whole-Body Hyperthermia (Sham WBH)
Sham whole-body hyperthermia (sham WBH) will be administered by trained research assistants. Preparation for the sham WBH session, the sham WBH session, and cool down will last 3.5 hours, with heating lasting approximately 90-100 minutes (and no longer than 140 minutes). The treatment will take place in an infrared sauna dome, and the sham WBH session will minimally impact core body temperature.
Sponsors
University of California, San Francisco
National Center for Complementary and Integrative Health (NCCIH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
Study clinicians, who perform clinical interviews and provide cognitive behavioral therapy (CBT) treatments, will be masked to participant condition.
Intervention model description
Participants are randomized to one of two study arms
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age of at least 18 years old * Current major depressive episode of at least 2 weeks duration as assessed by the Structured Clinical Interview for DSM-5 (SCID) and a Beck Depression Inventory-II (BDIII) score \> 21 at screening * Able to understand the nature of the study and able to provide written informed consent prior to conduct of any study procedures * Must have smartphone onto which the participant can download an app from Apple App or Google Play stores * Ability to lie supine (on back) for 2 hours (required for sauna sessions)
Exclusion criteria
* \>30% reduction in BDI-II score between Screen #1 and Screen #2 (conducted \~1 week after Screen #1) * Suicide attempt in the past 12 months defined using the SAMHSA suicidality question during the clinician-administered interview or active suicidal ideation as indexed by a score of 3 on the BDI-II suicidality item during the clinician-administered interview * Any of the following medical conditions: cardiovascular disease (other than controlled hypertension), seizure disorder, history of cerebrovascular accident (CVA) or other serious neurological condition (e.g. Parkinson's disease, multiple sclerosis, or dementia), current neoplasia, any active enclosed infection (e.g. dental abscess, joint infection), hemophilia or other cause for excessive bleeding (e.g. platelet disorder), or other medical condition that in the opinion of investigators may increase the risk of WBH * Comorbid psychiatric conditions or history of comorbid psychiatric conditions that might better explain depressive symptoms, including schizophrenia, schizoaffective disorder, Bipolar Disorder I, Obsessive Compulsive Disorder, Anorexia Nervosa, Bulimia Nervosa, Alcohol Dependence, or Drug Dependence * Known hypersensitivity to hyperthermia and/or infrared exposure * Inability to fit into the sauna device * Breast implants * Pregnancy, active lactation or intention to become pregnant during the study period * Use of any medication that might impact thermoregulatory capacity, including: Diuretics, barbiturates, beta-blockers, antipsychotic agents, anti-cholinergic agents or chronic use of antihistamines, aspirin (other than low-dose ASA for prophylactic purposes), medication prescribed for the treatment of depression (antidepressant medication \[ADM\]) including but not limited to: selective serotonin reuptake inhibitors \[SSRIs\], Serotonin and norepinephrine reuptake inhibitors \[SNRIs\], Monoamine oxidase inhibitors \[MAOIs\], Tricyclics \[TCAs\], and atypical antipsychotic and antidepressant medications (participants must have been free of these medications for at least 4 weeks), antibiotics (past 14 days), pain medication (opioids) due to procedure, e.g., dental procedure (past 14 days), Emergency contraception pill (past 14 days) any other medication that in the judgment of the PI would increase risk of study participation or introduce excessive variance into physiological or behavioral responses to WBH recent use (multiple consecutive doses) of: non-steroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, cytokine antagonists * Regular use of any nicotine products, including cigarettes, vapes, chewing tobacco, or other forms of nicotine (if use is not regular, must be willing to refrain for 24 hours before and 24 hours after WBH session) * Unwilling to refrain from using marijuana products and alcohol for the 24 hours before and 24 hours after WBH session * Unwilling to refrain from heavy exercise on the day of WBH sessions * Unwilling to refrain from engaging with sauna, hot yoga, cold plunges, cryotherapy, and hot tub/jacuzzi outside of study (prospective participant must not have engaged with any of these activities for 30 days prior to their baseline study visit). * Has begun new psychotherapy treatment in the prior 6 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Net Promoter Score, and Enrollment Likelihood | 12 weeks | Study acceptability was indexed by participant-reported net-promoter scores. This is a response to a single question: "How likely would you be to recommend \[participation in a study or treatment like this\] to a friend or family member with depression?" Net promoter scores range from 0 (would not recommend) to 10 (would definitely recommend). Study acceptability was also indexed by an additional patient-reported metric, Enrollment Likelihood. Enrollment likelihood was a response to the question: "How likely would you be to enroll in this study given your experience in this study?" and response options range from 1 (extremely unlikely) to 5 (extremely likely). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Beck Depression Inventory-II (BDI-II) | Baseline and 12 weeks | Change in BDI-II from baseline assessment to final assessment. Scores range from 0 to 63 and items are summed to create a total score; higher scores indicate greater depression symptoms. |
| Change in Patient-Reported Outcomes Measurement Information Systems (PROMIS) 8a Depression | Baseline and 12 weeks | Change in PROMIS8a Depression from baseline to final assessment. T scores are computed; higher scores indicate greater depression symptoms. A T-score of 60 indicates sub-clinical or elevated levels of depression. A T score of 50 indicates the population mean with a standard deviation of 10. |
| Change in Hamilton Depression Rating Scale 6-item (HAMD-6) Self-Report | Baseline and 12 weeks | Change in HAMD-6 from baseline to final assessment. Scores range from 0 to 22, and items are summed to create a total score; higher scores indicate greater depression symptoms. |
| Change in Patient-Reported Outcomes Measurement Information Systems (PROMIS) 4a Anxiety | Baseline and 12 weeks | Change in PROMIS4a Anxiety from baseline to final assessment. T scores are computed; higher scores indicate greater depression symptoms. A T-score of 60 indicates sub-clinical or elevated levels of anxiety. A T score of 50 indicates the population mean with a standard deviation of 10. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAshley E Mason, PhD
University of California, San Francisco
PRINCIPAL_INVESTIGATORFrederick M Hecht, MD
University of California, San Francisco
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Whole-body Hyperthermia (Active Treatment) Participants receive 8 cognitive behavioral therapy (CBT) sessions and 4 bi-weekly whole-body hyperthermia (WBH) sessions that raise core body temperature to 38.5 C. Each active WBH session (including preparation and post-session activities) is up to approximately 3.5 hours, and each CBT session is approximately 50 minutes.
Cognitive Behavioral Therapy (CBT): Cognitive Behavioral Therapy (CBT) is a behavioral (psychotherapeutic) intervention for major depressive disorder (MDD). A highly trained masters' or PhD-level clinician will administer 8 weekly CBT sessions (\
50 minutes each), following the standard cognitive behavioral therapy for depression protocol.
Active Whole-Body Hyperthermia (Active WBH): Active whole-body hyperthermia (active WBH) will be administered by trained research assistants. Preparation for the active WBH session, the active WBH session, and cool down will last 3.5 hours, with heating lasting approximately 90-100 minutes (and no longer than 140 minutes). The treatment will take place in an infrared sauna dome, and the active heating phase will last until the participants has achieved a core (rectal) temperature of 38.5 C. | 15 |
| Sham Whole-body Hyperthermia (Sham Treatment) Participants receive 8 cognitive behavioral therapy (CBT) sessions and 4 bi-weekly sham whole-body hyperthermia (WBH) sessions, which minimally raise body temperature. Each sham WBH session (including preparation and post-session activities) is up to approximately 3.5 hours, and each CBT session is approximately 50 minutes.
Cognitive Behavioral Therapy (CBT): Cognitive Behavioral Therapy (CBT) is a behavioral (psychotherapeutic) intervention for major depressive disorder (MDD). A highly trained masters' or PhD-level clinician will administer 8 weekly CBT sessions (\
50 minutes each), following the standard cognitive behavioral therapy for depression protocol.
Sham Whole-Body Hyperthermia (Sham WBH): Sham whole-body hyperthermia (sham WBH) will be administered by trained research assistants. Preparation for the sham WBH session, the sham WBH session, and cool down will last 3.5 hours, with heating lasting approximately 90-100 minutes (and no longer than 140 minutes). The treatment will take place in an infrared sauna dome, and the sham WBH session will minimally impact core body temperature. | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Active Whole-body Hyperthermia (Active Treatment) | Sham Whole-body Hyperthermia (Sham Treatment) | Total |
|---|---|---|---|
| Age, Continuous | 40.47 years STANDARD_DEVIATION 13.89 | 35.87 years STANDARD_DEVIATION 13.06 | 38.17 years STANDARD_DEVIATION 13.45 |
| Beck Depression Inventory II (BDI-II) | 32.73 Score on a scale STANDARD_DEVIATION 9.07 | 32.27 Score on a scale STANDARD_DEVIATION 7.76 | 32.50 Score on a scale STANDARD_DEVIATION 8.3 |
| Blood Pressure (SBP/DBP), mm Hg Diastolic Blood Pressure | 76.3 mm Hg STANDARD_DEVIATION 8.6 | 78.7 mm Hg STANDARD_DEVIATION 8.6 | 77.5 mm Hg STANDARD_DEVIATION 8.5 |
| Blood Pressure (SBP/DBP), mm Hg Systolic Blood Pressure | 114.2 mm Hg STANDARD_DEVIATION 14.2 | 113.0 mm Hg STANDARD_DEVIATION 17.2 | 113.6 mm Hg STANDARD_DEVIATION 15.5 |
| Body Mass Index (BMI), Kg/m^2 | 27.12 kg/m^2 (kilograms per meter-squared) STANDARD_DEVIATION 6.45 | 25.93 kg/m^2 (kilograms per meter-squared) STANDARD_DEVIATION 5.54 | 26.53 kg/m^2 (kilograms per meter-squared) STANDARD_DEVIATION 5.94 |
| Education (highest level completed) Associate's Degree | 1 Participants | 3 Participants | 4 Participants |
| Education (highest level completed) Bachelor's Degree | 8 Participants | 5 Participants | 13 Participants |
| Education (highest level completed) Doctoral Degree (e.g., PhD, EdD) | 0 Participants | 2 Participants | 2 Participants |
| Education (highest level completed) High School diploma or GED | 0 Participants | 0 Participants | 0 Participants |
| Education (highest level completed) Master's Degree | 5 Participants | 3 Participants | 8 Participants |
| Education (highest level completed) Professional Degree (e.g., MD, DDS, JD) | 0 Participants | 1 Participants | 1 Participants |
| Education (highest level completed) Some college | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized African American/Black | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 4 Participants | 5 Participants |
| Race/Ethnicity, Customized Latino/Hispanic | 5 Participants | 4 Participants | 9 Participants |
| Race/Ethnicity, Customized More than one race | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Unreported | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White/Caucasian | 7 Participants | 4 Participants | 11 Participants |
| Region of Enrollment United States | 15 participants | 15 participants | 30 participants |
| Sex: Female, Male Female | 11 Participants | 12 Participants | 23 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 14 / 15 | 6 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
Net Promoter Score, and Enrollment Likelihood
Study acceptability was indexed by participant-reported net-promoter scores. This is a response to a single question: How likely would you be to recommend \[participation in a study or treatment like this\] to a friend or family member with depression? Net promoter scores range from 0 (would not recommend) to 10 (would definitely recommend). Study acceptability was also indexed by an additional patient-reported metric, Enrollment Likelihood. Enrollment likelihood was a response to the question: How likely would you be to enroll in this study given your experience in this study? and response options range from 1 (extremely unlikely) to 5 (extremely likely).
Time frame: 12 weeks
Population: Study participants who completed the final study survey, Net Promoter Score
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Whole-body Hyperthermia (Active Treatment) | Net Promoter Score, and Enrollment Likelihood | Net Promoter Score (0-10) | 7.73 score on a scale | Standard Deviation 2.15 |
| Active Whole-body Hyperthermia (Active Treatment) | Net Promoter Score, and Enrollment Likelihood | Enrollment Likelihood (1-5) | 4.13 score on a scale | Standard Deviation 1.06 |
| Sham Whole-body Hyperthermia (Sham Treatment) | Net Promoter Score, and Enrollment Likelihood | Net Promoter Score (0-10) | 8.00 score on a scale | Standard Deviation 2.08 |
| Sham Whole-body Hyperthermia (Sham Treatment) | Net Promoter Score, and Enrollment Likelihood | Enrollment Likelihood (1-5) | 4.29 score on a scale | Standard Deviation 0.83 |
Secondary
Change in Beck Depression Inventory-II (BDI-II)
Change in BDI-II from baseline assessment to final assessment. Scores range from 0 to 63 and items are summed to create a total score; higher scores indicate greater depression symptoms.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Whole-body Hyperthermia (Active Treatment) | Change in Beck Depression Inventory-II (BDI-II) | -19.07 score on a scale | Standard Error 2.69 |
| Sham Whole-body Hyperthermia (Sham Treatment) | Change in Beck Depression Inventory-II (BDI-II) | -21.10 score on a scale | Standard Error 2.41 |
Secondary
Change in Hamilton Depression Rating Scale 6-item (HAMD-6) Self-Report
Change in HAMD-6 from baseline to final assessment. Scores range from 0 to 22, and items are summed to create a total score; higher scores indicate greater depression symptoms.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Whole-body Hyperthermia (Active Treatment) | Change in Hamilton Depression Rating Scale 6-item (HAMD-6) Self-Report | -6.42 score on a scale | Standard Error 1.3 |
| Sham Whole-body Hyperthermia (Sham Treatment) | Change in Hamilton Depression Rating Scale 6-item (HAMD-6) Self-Report | -7.16 score on a scale | Standard Error 1.12 |
Secondary
Change in Patient-Reported Outcomes Measurement Information Systems (PROMIS) 4a Anxiety
Change in PROMIS4a Anxiety from baseline to final assessment. T scores are computed; higher scores indicate greater depression symptoms. A T-score of 60 indicates sub-clinical or elevated levels of anxiety. A T score of 50 indicates the population mean with a standard deviation of 10.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Whole-body Hyperthermia (Active Treatment) | Change in Patient-Reported Outcomes Measurement Information Systems (PROMIS) 4a Anxiety | -7.24 T-score units | Standard Error 1.63 |
| Sham Whole-body Hyperthermia (Sham Treatment) | Change in Patient-Reported Outcomes Measurement Information Systems (PROMIS) 4a Anxiety | -7.51 T-score units | Standard Error 2.06 |
Secondary
Change in Patient-Reported Outcomes Measurement Information Systems (PROMIS) 8a Depression
Change in PROMIS8a Depression from baseline to final assessment. T scores are computed; higher scores indicate greater depression symptoms. A T-score of 60 indicates sub-clinical or elevated levels of depression. A T score of 50 indicates the population mean with a standard deviation of 10.
Time frame: Baseline and 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Whole-body Hyperthermia (Active Treatment) | Change in Patient-Reported Outcomes Measurement Information Systems (PROMIS) 8a Depression | -10.79 T-score units | Standard Error 2.66 |
| Sham Whole-body Hyperthermia (Sham Treatment) | Change in Patient-Reported Outcomes Measurement Information Systems (PROMIS) 8a Depression | -11.54 T-score units | Standard Error 2.84 |
Other Pre-specified
Sudden Gains in Antidepressant Responses
Sudden gain in BDI-II scores, defined as \>25% reduction in depression symptoms in between between two adjacent sauna sessions, account for more than 50% of total depression symptom improvement
Time frame: 2-3 weeks