HypErthermia as an Additional Treatment for the Biology and Experience of Depression: Study 2

NCT05708976 | Completed Results DMC FDA Device

• 2 other identifiers: 21-34246R34AT011221
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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).

Conditions

Major Depressive Disorder; Depression

Keywords

hyperthermia; heat therapy; passive heating

Outcome Measures

Primary Outcomes (1)

• 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).

  12 weeks

Secondary Outcomes (4)

• Change in Beck Depression Inventory-II (BDI-II)

  Baseline and 12 weeks

• Change in Patient-Reported Outcomes Measurement Information Systems (PROMIS) 8a Depression

  Baseline and 12 weeks

• Change in Hamilton Depression Rating Scale 6-item (HAMD-6) Self-Report

  Baseline and 12 weeks

• Change in Patient-Reported Outcomes Measurement Information Systems (PROMIS) 4a Anxiety

  Baseline and 12 weeks

Other Outcomes (1)

• Sudden Gains in Antidepressant Responses

  2-3 weeks

Study Arms (2)

Active Whole-body Hyperthermia (Active Treatment)

EXPERIMENTAL

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.

Behavioral: Cognitive Behavioral Therapy (CBT); Device: Active Whole-Body Hyperthermia (Active WBH)

Sham Whole-body Hyperthermia (Sham Treatment)

PLACEBO COMPARATOR

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.

Behavioral: Cognitive Behavioral Therapy (CBT); Device: Sham Whole-Body Hyperthermia (Sham WBH)

Interventions

Cognitive Behavioral Therapy (CBT) BEHAVIORAL

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 Treatment); Sham Whole-body Hyperthermia (Sham Treatment)

Active Whole-Body Hyperthermia (Active WBH) DEVICE

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.

Also known as: Active Sauna Sessions

Active Whole-body Hyperthermia (Active Treatment)

Sham Whole-Body Hyperthermia (Sham WBH) DEVICE

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.

Also known as: Sham Sauna Sessions

Sham Whole-body Hyperthermia (Sham Treatment)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• \>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

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (1)

University of California San Francisco

San Francisco, California, 94115, United States

Location

Related Publications (5)

• Mason AE, Fisher SM, Chowdhary A, Guvva E, Veasna D, Floyd E, Fender SB, Raison C. Feasibility and acceptability of a Whole-Body hyperthermia (WBH) protocol. Int J Hyperthermia. 2021;38(1):1529-1535. doi: 10.1080/02656736.2021.1991010.

  PMID: 34674592 BACKGROUND

• Janssen CW, Lowry CA, Mehl MR, Allen JJ, Kelly KL, Gartner DE, Medrano A, Begay TK, Rentscher K, White JJ, Fridman A, Roberts LJ, Robbins ML, Hanusch KU, Cole SP, Raison CL. Whole-Body Hyperthermia for the Treatment of Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2016 Aug 1;73(8):789-95. doi: 10.1001/jamapsychiatry.2016.1031.

  PMID: 27172277 BACKGROUND

• Hanusch KU, Janssen CH, Billheimer D, Jenkins I, Spurgeon E, Lowry CA, Raison CL. Whole-body hyperthermia for the treatment of major depression: associations with thermoregulatory cooling. Am J Psychiatry. 2013 Jul;170(7):802-4. doi: 10.1176/appi.ajp.2013.12111395. No abstract available.

  PMID: 23820835 BACKGROUND

• Mason AE, Hartogensis W, Chowdhary A, Siwik CJ, Pandya LS, Jung E, Lupesko-Persky O, Hartley E, Hopkins L, Roberts S, Borovinsky J, Nelson JC, Lowry CA, Patrick RP, Moran PJ, Raison CL, Hecht FM. A Randomized Trial Testing a Novel Mind and Body Intervention for Depression: Cognitive Behavioral Therapy (CBT) and Whole-Body Hyperthermia (WBH). Glob Adv Integr Med Health. 2025 Oct 22;14:27536130251387714. doi: 10.1177/27536130251387714. eCollection 2025 Jan-Dec.

  PMID: 41146956 RESULT

• Mason AE, Chowdhary A, Hartogensis W, Siwik CJ, Lupesko-Persky O, Pandya LS, Roberts S, Anglo C, Moran PJ, Nelson JC, Lowry CA, Patrick RP, Raison CL, Hecht FM. Feasibility and acceptability of an integrated mind-body intervention for depression: whole-body hyperthermia (WBH) and cognitive behavioral therapy (CBT). Int J Hyperthermia. 2024;41(1):2351459. doi: 10.1080/02656736.2024.2351459. Epub 2024 May 14.

  PMID: 38743265 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depression; Hyperthermia

Interventions

Cognitive Behavioral Therapy

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Heat Stress Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Results Point of Contact

• Title: Ashley E. Mason, PhD
• Organization: University of California San Francisco

ashley.mason@ucsf.edu

4155146820

Study Officials

• Ashley E Mason, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Frederick M Hecht, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Study clinicians, who perform clinical interviews and provide cognitive behavioral therapy (CBT) treatments, will be masked to participant condition.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are randomized to one of two study arms

Study Record Dates

• First Submitted: January 23, 2023
• First Posted: February 1, 2023
• Study Start: February 15, 2023
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2024
• Last Updated: May 27, 2026
• Results First Posted: October 30, 2025

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)