Whole-Body Hyperthermia for Mood and Anxiety Disorders

Sponsor

Weill Medical College of Cornell University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06144294

Collaborator

(none)

240

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This study aims to examine the scientific mechanisms of whole-body hyperthermia (WBH), a novel, rapidly acting, single session antidepressant and anxiolytic therapy. It also aims to determine its feasibility and acceptability in women with postpartum depression (PPD). The study will enroll four cohorts of participants: healthy postpartum controls; postpartum women with PPD; healthy adult controls; and adults with major depressive disorder or anxiety disorders in a longitudinal protocol.

Condition or Disease	Intervention/Treatment	Phase
Postpartum Depression Mood Disorders Anxiety Disorders Postpartum Anxiety	Other: Whole-Body Hyperthermia Diagnostic Test: fMRI	N/A

Detailed Description

Whole-body hyperthermia has already been shown to be feasible, acceptable, and effective in major depressive disorder (MDD) populations, with an open-label study and a subsequent randomized, double-blind, sham-controlled study both demonstrating efficacy. Some evidence indicates that the antidepressant effect may be due to immune mechanisms, though it may also be mediated through direct neural effects of hyperthermia

This project aims to establish a protocol to deliver WBH therapy to patients with mood and anxiety disorders to collect information about scientific mechanisms. It also seeks to extend treatment to a specific population: a single session WBH treatment could be of tremendous interest to depressed postpartum women who wish to avoid medications and time away from their infants.

The mechanistic work will be completed with the four cohorts. By examining mechanisms in all four groups, we will be able to determine mechanisms unique to ill individuals as well as any mechanistic differences between MDD and PPD. In addition, we aim to establish feasibility and acceptability of this protocol in postpartum women. Why? Over 80% of women deliver a child, and 15-20% of all women develop significant postpartum mental illness, usually depression and anxiety.

Participants will be divided into two groups: those undergoing a simplified protocol to test feasibility and acceptability in the postpartum (Study Group 1) and those undergoing a more time-intensive protocol to evaluate mechanisms (Study Group 2). In addition, participants in Study Group 2 will be eligible to enroll in a sub-study (Study Group 3) including up to 10 fMRI session.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

240 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Whole-Body Hyperthermia for Mood and Anxiety Disorders

Anticipated Study Start Date :

Nov 1, 2023

Anticipated Primary Completion Date :

Nov 1, 2027

Anticipated Study Completion Date :

Nov 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 2 - Cohort 2a Healthy women or transgender men 18-50 years of age, <6 months postpartum	Other: Whole-Body Hyperthermia The Clearlight dome sauna is portable infrared sauna consisting of two lightweight domes and an infrared heating pad. The sauna will be used to deliver the intervention to the participant and the sauna session will end as soon as (1) an internal body temperature of 38.5 C (101.3 F) is reached for two consecutive minutes or, (2) 140 minutes have passed. Other Names: Clearlight Portable Dome Sauna
Experimental: Group 2 - Cohort 2b Women and transgender men 18-50 years of age, <6 months postpartum, meeting criteria for a major depressive episode in the postpartum period on the MINI	Other: Whole-Body Hyperthermia The Clearlight dome sauna is portable infrared sauna consisting of two lightweight domes and an infrared heating pad. The sauna will be used to deliver the intervention to the participant and the sauna session will end as soon as (1) an internal body temperature of 38.5 C (101.3 F) is reached for two consecutive minutes or, (2) 140 minutes have passed. Other Names: Clearlight Portable Dome Sauna
Experimental: Group 2 - Cohort 2c Healthy adults of both sexes 18-50 years of age	Other: Whole-Body Hyperthermia The Clearlight dome sauna is portable infrared sauna consisting of two lightweight domes and an infrared heating pad. The sauna will be used to deliver the intervention to the participant and the sauna session will end as soon as (1) an internal body temperature of 38.5 C (101.3 F) is reached for two consecutive minutes or, (2) 140 minutes have passed. Other Names: Clearlight Portable Dome Sauna
Experimental: Group 2 - Cohort 2d Adults of both sexes 18-50 years of age meeting criteria for an episode of major depression or generalized anxiety disorder on the MINI	Other: Whole-Body Hyperthermia The Clearlight dome sauna is portable infrared sauna consisting of two lightweight domes and an infrared heating pad. The sauna will be used to deliver the intervention to the participant and the sauna session will end as soon as (1) an internal body temperature of 38.5 C (101.3 F) is reached for two consecutive minutes or, (2) 140 minutes have passed. Other Names: Clearlight Portable Dome Sauna
Experimental: Group 3 - Cohort 2a Healthy women or transgender men 18-50 years of age, <6 months postpartum	Other: Whole-Body Hyperthermia The Clearlight dome sauna is portable infrared sauna consisting of two lightweight domes and an infrared heating pad. The sauna will be used to deliver the intervention to the participant and the sauna session will end as soon as (1) an internal body temperature of 38.5 C (101.3 F) is reached for two consecutive minutes or, (2) 140 minutes have passed. Other Names: Clearlight Portable Dome Sauna Diagnostic Test: fMRI A standard magnetic resonance imaging (fMRI) machine will be used to take images of the brain.
Experimental: Group 3 - Cohort 2b Women and transgender men 18-50 years of age, <6 months postpartum, meeting criteria for a major depressive episode in the postpartum period on the MINI	Other: Whole-Body Hyperthermia The Clearlight dome sauna is portable infrared sauna consisting of two lightweight domes and an infrared heating pad. The sauna will be used to deliver the intervention to the participant and the sauna session will end as soon as (1) an internal body temperature of 38.5 C (101.3 F) is reached for two consecutive minutes or, (2) 140 minutes have passed. Other Names: Clearlight Portable Dome Sauna Diagnostic Test: fMRI A standard magnetic resonance imaging (fMRI) machine will be used to take images of the brain.
Experimental: Group 3 - Cohort 2c Healthy adults of both sexes 18-50 years of age	Other: Whole-Body Hyperthermia The Clearlight dome sauna is portable infrared sauna consisting of two lightweight domes and an infrared heating pad. The sauna will be used to deliver the intervention to the participant and the sauna session will end as soon as (1) an internal body temperature of 38.5 C (101.3 F) is reached for two consecutive minutes or, (2) 140 minutes have passed. Other Names: Clearlight Portable Dome Sauna Diagnostic Test: fMRI A standard magnetic resonance imaging (fMRI) machine will be used to take images of the brain.
Experimental: Group 3 - Cohort 2d Adults of both sexes 18-50 years of age meeting criteria for an episode of major depression or generalized anxiety disorder on the MINI	Other: Whole-Body Hyperthermia The Clearlight dome sauna is portable infrared sauna consisting of two lightweight domes and an infrared heating pad. The sauna will be used to deliver the intervention to the participant and the sauna session will end as soon as (1) an internal body temperature of 38.5 C (101.3 F) is reached for two consecutive minutes or, (2) 140 minutes have passed. Other Names: Clearlight Portable Dome Sauna Diagnostic Test: fMRI A standard magnetic resonance imaging (fMRI) machine will be used to take images of the brain.

Outcome Measures

Primary Outcome Measures

Percent change in EEG amplitude. [During the course of the intervention: when participant core temperature reaches 38.5 C for two consecutive minutes OR after 140 minutes have passed.]
Measure the extent of broad-band neural suppression in WBH.
Percent change in EEG frequency. [During the course of the intervention: when participant core temperature reaches 38.5 C for two consecutive minutes OR after 140 minutes have passed.]
Measure the extent of broad-band neural suppression in WBH,

Secondary Outcome Measures

Mean change from baseline in inflammatory activity as measured by pro-inflammatory cytokines. [Two days prior to the intervention; immediately prior to intervention; immediately post-intervention; and at five days post-intervention.]
Determine whether peripheral immune activation predicts the effect of WBH on PPD or depressive and anxiety symptoms in non-postpartum adults.
Mean change in average 24-hour core temperature. [Two days prior to the intervention and five days post-intervention.]
Determine the average change in core temperature across the whole-body hyperthermia intervention.
Individualized precision functional brain maps. [Up to 3 fMRI scans in the 10 days before the intervention and up to 7 fMRI scans in the 6 weeks post-intervention.]
Determine longitudinal changes in neural circuit activity produced by whole-body hyperthermia.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria

Study Group 2
Arm 1: Healthy women or transgender men 18-50 years of age, ≤ 6 months postpartum
Arm 2: Women and transgender men 18-50 years of age, ≤ 6 months postpartum, meeting criteria for a major depressive episode in the postpartum period on the MINI.
Arm 3: Healthy adults of both sexes 18-50 years of age.
Arm 4: Adults of both sexes 18-50 years of age meeting criteria for an episode of major depression or generalized anxiety disorder on the Mini International Neuropsychiatric Interview (MINI)
Study Group 3
Subjects enrolled in Study Group 2 are eligible for an optional additional sub-study (Study Group 3); inclusion criteria are the same as for Study Group 2.

Exclusion criteria for all:

For logistics, we will exclude individuals with BMI >30 and waist size > 35, who may not fit comfortably in the sauna dome for all cohorts described above.
For contraindications to hyperthermia, we will exclude from all cohorts listed above, individuals with severe cardiovascular disease, including congestive heart failure, coronary artery disease, uncontrolled hypertension, and hypotension; pregnancy; active substance use disorders; recent major injuries or surgeries (<1 week prior); impaired sweating (those with multiple sclerosis, diabetes mellitus with neuropathy, central nervous system disease, heat insensitivity); a history or family history of malignant hyperthermia, fever or active signs of infection; taking medications that may have interactions with hyperthermia (for example, barbiturates, diuretics, and beta blockers) and the use of an antipyretic medication in the 12 hours prior to the WBH intervention. Individuals with above mentioned conditions will be excluded since either WBH might deteriorate their conditions or it is unknown how their condition will be affected by WBH.
For contraindications to immune analyses, we will exclude individuals with conditions that might affect immune analyses, including individuals with known active autoimmune or endocrine disease and individuals with active infection at baseline.

Additional exclusion criteria by cohort or applicable study group:

Study Group 2
Arm 1: For psychiatric contraindications, we will exclude individuals with a history of psychiatric disorders as assessed by MINI since the cohort will consist of mentally healthy individuals as a control group.
Arm 2: For psychiatric contraindications, we will exclude individuals with bipolar disorder or other Axis I psychiatric disorders except depressive and anxiety disorders and individuals taking antidepressants who are unwilling to hold antidepressant dose steady from recruitment through study termination. In this cohort we exclude individuals with other psychiatric disorders except depressive and anxiety disorders to rule out the effect of other psychiatric diseases on the outcome.
Arm 3: For psychiatric contraindications, we will exclude individuals with a history of psychiatric disorders as assessed by MINI since the cohort will consist of mentally healthy individuals as a control group.
Arm 4: For psychiatric contraindications, we will exclude individuals with bipolar disorder or other Axis I psychiatric disorders except depressive and anxiety disorders and individuals taking antidepressants who are unwilling to hold antidepressant dose steady from recruitment through study termination. In this cohort we exclude individuals with other psychiatric disorders except depressive and anxiety disorders to rule out the effect of other psychiatric diseases on the outcome.
Study Group 2 and Study Group 3 - All participants
For contraindications to use of the e-Celsius capsule that will be used to measure core temperature, we will exclude individuals with pacemakers or any other electric medical implant, individuals with a current intestinal disorder that could lead to obstruction of the digestive tract including gastroparesis, individuals with history of diverticula, individuals with history of past surgical procedures in the gastrointestinal tract, individuals with a swallowing disorder and individuals with Crohn's disease.
Study Group 3 - All participants
For contraindications to MRI, individuals with metal in the body will be excluded from participating in the MRI portion of the research since magnetic fields in MRI scanners can cause dangerous interactions in patients with metallic foreign bodies: projectile effect, twisting, burning, artifacts, and device malfunction (interference with a pacemaker).

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Weill Medical College of Cornell University

Investigators

Principal Investigator: Lauren M Osborne, PhD, Weill Medical College of Cornell University
Principal Investigator: Jonathan Power, MD, PhD, Weill Medical College of Cornell University