HypErthermia as an Additional Treatment for the Biology and Experience of Depression: Study 2 (HEATBED2)

• ClinicalTrials.gov Identifier: NCT05708976
• Recruitment Status: Recruiting
• First Posted: February 1, 2023
• Last Update Posted: February 13, 2023
• Sponsor: University of California, San Francisco
• Collaborator: National Center for Complementary and Integrative Health (NCCIH)
• Information provided by (Responsible Party): University of California, San Francisco

Tracking Information

• First Submitted Date: January 23, 2023
• First Posted Date: February 1, 2023
• Last Update Posted Date: February 13, 2023
• Actual Study Start Date: January 27, 2023
• Estimated Primary Completion Date: October 31, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 23, 2023)

Net Promoter Score [ Time Frame: 12 weeks ]

Study acceptability will be 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).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 23, 2023)

• Change in Beck Depression Inventory-II (BDI-II) [ Time Frame: 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 [ Time Frame: Baseline and 12 weeks ]
  Change in PROMIS8a Depression from baseline to final assessment. T scores are computed; higher scores indicate greater depression symptoms.
• Change in Hamilton Depression Rating Scale 6-item (HAMD-6) Self-Report [ Time Frame: 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 [ Time Frame: Baseline and 12 weeks ]
  Change in PROMIS4a Anxiety from baseline to final assessment. T scores are computed; higher scores indicate greater depression symptoms.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: January 23, 2023)

Sudden gains in antidepressant responses [ Time Frame: 2-3 weeks ]

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

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: HypErthermia as an Additional Treatment for the Biology and Experience of Depression: Study 2
• Official Title: HypErthermia as an Additional Treatment for the Biology and Experience of Depression: Study 2
• 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.
• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Participants are randomized to one of two study arms

Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Masking Description:

Study clinicians, who perform clinical interviews and provide cognitive behavioral therapy (CBT) treatments, will be masked to participant condition.

Primary Purpose: Treatment

Condition

• Major Depressive Disorder
• Depression

Intervention

• Behavioral: 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.
• Device: 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.
  Other Name: Active Sauna Sessions
• Device: 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.
  Other Name: Sham Sauna Sessions

Study Arms

• Experimental: 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.
  Interventions:

  • Behavioral: Cognitive Behavioral Therapy (CBT)
  • Device: Active Whole-Body Hyperthermia (Active WBH)
• Placebo Comparator: 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.
  Interventions:

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

Publications *

• 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.
• 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. Erratum In: JAMA Psychiatry. 2016 Aug 1;73(8):878.
• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 23, 2023): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 31, 2024
• Estimated Primary Completion Date: October 31, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Anoushka Chowdhary, BA; 415 514 8445; heatbed@ucsf.edu

Contact: Claudine Anglo, BS; 415 514 8445; heatbed@ucsf.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05708976
• Other Study ID Numbers: 21-34246; R34AT011221 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University of California, San Francisco
• Original Responsible Party: Same as current
• Current Study Sponsor: University of California, San Francisco
• Original Study Sponsor: Same as current
• Collaborators: National Center for Complementary and Integrative Health (NCCIH)

Investigators

• Principal Investigator: Ashley E Mason, PhD; University of California, San Francisco
• Principal Investigator: Frederick M Hecht, MD; University of California, San Francisco

• PRS Account: University of California, San Francisco
• Verification Date: February 2023