Major Depressive Disorder
Conditions
Brief summary
This single-arm feasibility trial administered up to 8 weekly (early phase) or 4 bi-weekly (later phase) whole-body hyperthermia (WBH) sessions and 8 weekly cognitive behavioral therapy (CBT) 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 WBH may be particularly effective in combination with cognitive behavioral therapy (CBT), an established treatment for depression. This work holds important promise to improve treatment of depression and advance understanding of the role of integrated mind-body therapies for mood disorders. This single-arm feasibility trial piloted and optimized procedures for integrating WBH (initially 8 weekly sessions). During the course of this feasibility trial, with oversight and permission from the Sponsor, the 8 weekly WBH sessions were reduced to 4 bi-weekly WBH sessions to improve feasibility.
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.
DEVICEWhole-Body Hyperthermia (WBH)
Whole-body hyperthermia (WBH) will be administered by trained research assistants. Preparation for the WBH, the WBH session, and cool down will last 3.5-4 hours, with active WBH lasting up to approximately 140 minutes. WBH 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 101.3 F.
Sponsors
University of California, San Francisco
National Center for Complementary and Integrative Health (NCCIH)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Current major depressive episode of at least 4 weeks duration as assessed by the Structured Clinical Interview for DSM-5 (SCID) and a Beck Depression Inventory-II (BDI-II) score greater than or equal to 21 at screening * Age of at least 18 years old * Must have smartphone onto which they can download an app from Apple App or Google Play stores * English speaking * Ability to lie supine (on back) for 2 hours (required for WBH sessions) * Must be fully vaccinated against COVID-19
Exclusion criteria
* Greater than 30 percent reduction in BDI-II score between Screen 1 and Screen 2 (conducted about 1 week after Screen 1) * Suicide attempt within the prior 12 months and/or severe current suicidal ideation * 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 * Inability to fit into the sauna device * Known hypersensitivity to hyperthermia and/or infrared exposure * 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) * 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 * Greater than 30 percent reduction in Beck Depression Inventory-II (BDI-II) score between Screen 1 and Screen 2 * Has begun new psychotherapy treatment in the prior 6 weeks * 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 each WBH session) * Unwilling to refrain from using marijuana products and alcohol for the 24 hours before and 24 hours after each WBH session * Unwilling to refrain from sauna use outside of study procedures during study participation, and must not have used a sauna for more than 20 minutes on any single occasion in the 60 days before the screen 2/baseline study visit, and must not have used a sauna in the 30 days before the screen 2/baseline study visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Number of Planned WBH Sessions Completed | 12 weeks | Investigators will average and report the number of completed WBH sessions (4 bi-weekly WBH sessions or 8 weekly WBH sessions offered to participants). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Number of Planned Beck Depression Inventory-II (BDI-II) Assessments Completed | 12 weeks | Investigators will average and report the number of completed BDI-II assessments (10 planned per participant) |
| Change in Beck Depression Inventory-II (BDI-II) From Baseline to 12-week Assessment | Baseline and 12 weeks | Change in BDI-II from baseline assessment to final assessment. BDI-II scores range from 0 to 63 with higher scores indicating more severe depression symptoms. |
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
Pre-assignment details
Midway through this feasibility trial, with oversight and permission from the Sponsor, the 8 weekly WBH sessions (n=6 participants) were reduced to 4 bi-weekly WBH sessions (n=10 participants) to improve feasibility.
Participants by arm
| Arm | Count |
|---|---|
| Cognitive Behavioral Therapy (CBT) and 8 Sessions Whole-Body Hyperthermia (WBH) Participants receive up to 8 weekly whole-body hyperthermia (WBH) sessions and 8 weekly cognitive behavioral therapy (CBT) sessions.
Whole-Body Hyperthermia (WBH): Whole-body hyperthermia (WBH) will be administered by trained research assistants. Preparation for the WBH, the WBH session, and cool down lasts 3.5-4 hours, with active WBH lasting up to approximately 140 minutes. WBH takes place in an infrared sauna dome, and the active heating phase lasts until participants achieve a core (rectal) temperature of 101.3 F.
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. | 6 |
| Cognitive Behavioral Therapy (CBT) and 4 Sessions Whole-Body Hyperthermia Participants receive up to 4 bi-weekly whole-body hyperthermia (WBH) sessions and 8 weekly cognitive behavioral therapy (CBT) sessions.
Whole-Body Hyperthermia (WBH): Whole-body hyperthermia (WBH) will be administered by trained research assistants. Preparation for the WBH, the WBH session, and cool down lasts 3.5-4 hours, with active WBH lasting up to approximately 140 minutes. WBH takes place in an infrared sauna dome, and the active heating phase lasts until participants achieve a core (rectal) temperature of 101.3 F.
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. | 10 |
| Total | 16 |
Baseline characteristics
| Characteristic | Cognitive Behavioral Therapy (CBT) and 8 Sessions Whole-Body Hyperthermia (WBH) | Cognitive Behavioral Therapy (CBT) and 4 Sessions Whole-Body Hyperthermia | Total |
|---|---|---|---|
| Age, Continuous | 41.2 years STANDARD_DEVIATION 17.3 | 42.4 years STANDARD_DEVIATION 9.7 | 41.9 years STANDARD_DEVIATION 12.6 |
| Beck Depression Inventory-II (BDI-II) | 27.83 units on a scale STANDARD_DEVIATION 2.93 | 30.40 units on a scale STANDARD_DEVIATION 6.64 | 29.44 units on a scale STANDARD_DEVIATION 5.56 |
| Race/Ethnicity, Customized African American/Black | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Latino/Hispanic | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized More Than One Race | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Native American | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White/Caucasian | 3 Participants | 6 Participants | 9 Participants |
| Region of Enrollment United States | 6 participants | 10 participants | 16 participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 9 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 10 |
| other Total, other adverse events | 5 / 6 | 6 / 10 |
| serious Total, serious adverse events | 0 / 6 | 0 / 10 |
Outcome results
Primary
Average Number of Planned WBH Sessions Completed
Investigators will average and report the number of completed WBH sessions (4 bi-weekly WBH sessions or 8 weekly WBH sessions offered to participants).
Time frame: 12 weeks
Population: This feasibility trial piloted and optimized procedures for integrating WBH. The study was planned to be single-arm, but midway through this trial, with oversight and permission from the Sponsor, the 8 weekly WBH sessions (n=6 participants) were reduced to 4 bi-weekly WBH sessions (n=10 participants) to improve feasibility; results are here presented separately by number of WBH sessions offered.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Behavioral Therapy (CBT) and 8 Sessions Whole-Body Hyperthermia (WBH) | Average Number of Planned WBH Sessions Completed | 7.83 Count of WBH Sessions | Standard Deviation 0.41 |
| Cognitive Behavioral Therapy (CBT) and 4 Sessions Whole-Body Hyperthermia (WBH) | Average Number of Planned WBH Sessions Completed | 3.20 Count of WBH Sessions | Standard Deviation 1.4 |
Secondary
Average Number of Planned Beck Depression Inventory-II (BDI-II) Assessments Completed
Investigators will average and report the number of completed BDI-II assessments (10 planned per participant)
Time frame: 12 weeks
Population: All participants were offered 8 CBT sessions and administered 10 BDI-II assessments. This feasibility trial piloted and optimized procedures for integrating WBH. The study was planned to be single-arm, but midway through this trial, with oversight and permission from the Sponsor, the 8 weekly WBH sessions (n=6 participants) were reduced to 4 bi-weekly WBH sessions (n=10 participants) to improve feasibility; results are here presented separately by number of WBH sessions offered.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive Behavioral Therapy (CBT) and 8 Sessions Whole-Body Hyperthermia (WBH) | Average Number of Planned Beck Depression Inventory-II (BDI-II) Assessments Completed | 9.3 Assessments Completed | Standard Deviation 1.6 |
| Cognitive Behavioral Therapy (CBT) and 4 Sessions Whole-Body Hyperthermia (WBH) | Average Number of Planned Beck Depression Inventory-II (BDI-II) Assessments Completed | 8.7 Assessments Completed | Standard Deviation 2.6 |
Secondary
Change in Beck Depression Inventory-II (BDI-II) From Baseline to 12-week Assessment
Change in BDI-II from baseline assessment to final assessment. BDI-II scores range from 0 to 63 with higher scores indicating more severe depression symptoms.
Time frame: Baseline and 12 weeks
Population: Midway through this feasibility trial, with oversight and permission from the Sponsor, the 8 weekly WBH sessions (n=6 participants) were reduced to 4 bi-weekly WBH sessions (n=10 participants) to improve feasibility.~All participants were offered 8 CBT sessions and 10 BDI-II assessments. n=6 offered 8 WBH sessions: n=5 completed the final assessment n=10 offered 4 WBH sessions: n=7 completed the final assessment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cognitive Behavioral Therapy (CBT) and 8 Sessions Whole-Body Hyperthermia (WBH) | Change in Beck Depression Inventory-II (BDI-II) From Baseline to 12-week Assessment | -16.80 score on a scale |
| Cognitive Behavioral Therapy (CBT) and 4 Sessions Whole-Body Hyperthermia (WBH) | Change in Beck Depression Inventory-II (BDI-II) From Baseline to 12-week Assessment | -15.14 score on a scale |