Multi-site Feasibility of an Integrated Treatment for the Biology and Experience of Depression: The MULTIBED Study

Official title

Assessing Multi-site Feasibility of an Integrated Whole-body Hyperthermia and Behavioral Intervention for Major Depressive Disorder: The MULTIBED Study

Overview

This randomized 2x2 factorial intervention trial administers 8 weekly cognitive behavioral therapy (CBT) sessions (yes/no) and 4 bi-weekly active whole-body hyperthermia (WBH) sessions (yes/no) to adults aged 18 years or older with major depressive disorder (MDD).

Detailed description

Major Depressive Disorder afflicts more than hundreds of millions of 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 randomized 2x2 factorial intervention trial administers 8 weekly cognitive behavioral therapy (CBT) sessions (yes/no) and 4 bi-weekly active whole-body hyperthermia (WBH) sessions (yes/no) to adults aged 18 years or older with major depressive disorder (MDD). This work holds important promise to improve the treatment of depression and to advance understanding of the role of integrated mind-body therapies for mood disorders.

Interventions

• 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 Whole-Body Hyperthermia
  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.

Primary outcome measures

• Retention [Time frame: 12 weeks]
• CBT Intervention Fidelity [Time frame: 12 weeks]
• WBH Intervention Fidelity [Time frame: 12 weeks]
• Study Assessment Completion [Time frame: 6 months]

Eligibility criteria

Inclusion criteria

• 18 years or older
• Able to read and speak in English
• Able to understand the nature of the study and able to provide written informed consent
• Current major depressive episode of at least 2 weeks duration as assessed by the Structured Clinical Interview for DSM-5 (SCID) and a Patient Health Questionnaire - 8 (PHQ-8) score of 10 or greater at screening
• Willing to use a form of pregnancy contraceptive (e.g., barrier methods such as condoms, oral contraception, or other birth control type) if assigned female sex at birth and premenopausal
• Able to lie supine for 2 hours in a sauna device
• Access to the internet via computer, smartphone, or tablet

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), or 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Factorial

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 3 centers

• University of California, San Francisco, Osher Center for Integrative Health — San Francisco
• Massachusetts General Hospital (MGH) — Boston
• Cleveland Clinic Foundation — Cleveland

Publications

• 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 20 PMID 38743265
• 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;14:2753613025138 PMID 41146956

Identifiers

NCT: NCT07596914 · MULTIBED · R01AT013214

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗