The Brain on Whole Body Hyperthermia: A Neuroimaging Study

Summary

The investigators have observed in an open trial that a single session of whole body hyperthermia (WBH) induced rapid antidepressant effects that persisted for at least a week in patients with major depression (MDD) severe enough to warrant inpatient hospitalization. In addition to reducing depression, the single session of WBH induced a prolonged reduction in mean core body temperature, consistent with basic science data from our group suggesting that hyperthermia activates a skin-to-brain pathway that have been shown in animals to be important for mood and body temperature regulation. Consistent with this known anatomy in our preliminary study in depressed patients, reductions in core body temperature were highly correlated with reductions in depressive symptoms over the same time period (one week post WBH). Moreover, patients with higher mean core body temperature prior to treatment had enhanced antidepressant effects. Because increased body temperature is an outcome of poor functioning in the skin-to-brain pathway activated by WBH our data suggests that WBH may actually sensitize this pathway in ways that promote changes in brain functioning known to promote emotional well-being. The results of our first open trial have encouraged us to conduct a larger, more rigorous placebo-controlled, double blind study of WBH for MDD, which is currently underway at the University of Arizona Medical School. Missing from our assessments in this ongoing double-blind study is any measure of the impact of WBH on brain function. The current proposal addresses ths gap in our investigative portfolio by proposing to conduct a second, randomized trial of active vs. sham WBH that will examine the impact of WBH on measures of brain function known from prior studies to be important for both depression and its treatment.

Conditions

• Major Depression

Interventions

DEVICE

High intensity whole-body infrared heating

The Whole Body Hyperthermia system uses water-filtered infrared-A (wIRA) heat radiation. The rise in the body's core temperature is correspondingly rapid and well-tolerated. There are two phases of the thermal challenge, 1) Irradiation phase during which the patient lies recumbent with his/her head positioned outside the tent. The wIRA irradiators are arranged above the exposed upper part of the body; and 2) Heat retention phase during which the patient lies in the chamber with the walls of the tent positioned to retain heat. Core body temperatures will be raised to those comparable to a mild fever 37.8-38.5°C.

DEVICE

Low intensity whole-body infrared heating

Attenuated heating using only heating coils at the bottom of the Heckel device. This results in only a minor increase in skin temperature and no increase in core body temperature. The participant will still feel heat and will see similar lighting and hear similar sounds as those occurring during actual WBH, and will be in the chamber for the same period of time.

DEVICE

Functional Magnetic Resonance Imaging (fMRI) and electrocardiogram (EKG)

A standard magnetic resonance imaging (fMRI) machine will be used to take images of the brain. An standard EKG (compatible with the fMRI machine) will be used to take measurements of cardiac vagal control.

OTHER

Questionnaires

Weekly questionnaires to assess changes in depression, mood, perceptions of self and quality of life will be administered.

Sponsors & Collaborators

• University of Arizona

  lead OTHER

Principal Investigators

• Charles Raison, MD · University of Arizona, Department of Psychiatry, College of Medicine

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

30 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2014-02-28

Primary Completion

2015-05-31

Completion

2015-05-31

Countries

• United States

Study Locations