The Brain on Whole Body Hyperthermia: A Neuroimaging Study

NCT02062840 | Completed

• 1 other identifier: 13-121-670-10
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Whole Body Hyperthermia; Functional Magnetic Resonance Imaging; EEG

Outcome Measures

Primary Outcomes (2)

• Change in acute brain effects of WBH on resting state brain connectivity and function

  Functional magnetic resonance imaging (fMRI) analyses of resting state brain connectivity.

  Change from baseline in resting state brain connectivity and one day following WBH/WBH-control Treatment.

• Degree of concordance of brain activity with autonomic nervous system function

  Functional magnetic resonance imaging (fMRI) analyses of concordance between subgenual anterior cingulate cortex and autonomic nervous system function assessed by electrocardiogram (EKG). The investigators are specifically looking at the inter-relationship between cardiac vagal control and brain activity.

  Change from baseline in concordance between subgenual anteriori cingulate cortex and autonomic nervous system function and one day following WBH/WBH-control Treatment.

Secondary Outcomes (4)

• Change in depression scores over time.

  Seven days prior to WBH/WBH-control treatment, the day of and two days immediately following WBH/WBH-control treatment, and 7 days following WBH/WBH-control treatment.

• Change in Positive and Negative Affect

  Seven days prior to WBH/WBH-control treatment, the day of and two days immediately following WBH/WBH-control treatment, and 7 days follwoing WBH/WBH-control treatment.

• Change in ability to function in daily life

  Seven days prior to WBH/WBH-control treatment, the day of and two days immediately following WBH/WBH-control treatment, and 7 days following WBH/WBH-control treatment.

• Change in quality of life

  Seven days prior to WBH/WBH-control treatment, the day of and two days immediately following WBH/WBH-control treatment, and 7 days following WBH/WBH-control treatment.

Study Arms (2)

High intensity whole-body infrared heating and Neuroimaging

EXPERIMENTAL

Subjects will have an fMRI the morning of their WBH session and and fill out study questionnaires. Following the fMRI session, the participant will undergo the WBH intervention where subjects will be induced to levels of heat that increases core body temperature to approximately 37.5-38.5 °C.temperature.

Device: High intensity whole-body infrared heating; Device: Functional Magnetic Resonance Imaging (fMRI) and electrocardiogram (EKG); Other: Questionnaires

Low intensity whole-body infrared heating and

SHAM COMPARATOR

Subjects will have an fMRI the morning of their WBH session and and fill out study questionnaires. Following the fMRI session, the participant will undergo the WBH-control intervention where subjects will be induced to levels of heat that causes only a minor increase in body temperature.

Device: Low intensity whole-body infrared heating; Device: Functional Magnetic Resonance Imaging (fMRI) and electrocardiogram (EKG); Other: Questionnaires

Interventions

High intensity whole-body infrared heating DEVICE

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.

High intensity whole-body infrared heating and Neuroimaging

Low intensity whole-body infrared heating DEVICE

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.

Low intensity whole-body infrared heating and

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

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.

High intensity whole-body infrared heating and Neuroimaging; Low intensity whole-body infrared heating and

Questionnaires OTHER

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

High intensity whole-body infrared heating and Neuroimaging; Low intensity whole-body infrared heating and

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female aged 18-30.
• Able to understand the nature of the study and able to provide written informed consent prior to conduct of any study procedures.
• Fluent English Speakers (for fMRI purposes)
• Right-handed (for fMRI purposes)
• For women of child-bearing potential (i.e., one who is biologically capable of becoming pregnant), must be willing to use a medically acceptable form of birth control or practice abstinence for the duration of her participation in the trial.
• Beck Depression Inventory-II Score of ≥14 (Moderate depression)
• Normal or corrected to normal vision and normal hearing (for fMRI purposes)

You may not qualify if:

• Any of the following diagnoses, as identified by the intake evaluation conducted or study assessments:
• A diagnosis claustrophobia severe enough that it would impair ability to be in the Heckel HT3000 hyperthermia device and/or the fMRI machine.
• A current (or within 12 months prior to the Screening visit) diagnosis of Anorexia Nervosa or Bulimia Nervosa
• A current (within 1 month prior to screening visit) diagnosis of substance dependence
• Lifetime history of schizophrenia or bipolar I disorder
• Use of psychotropic medications within 2 weeks of screening (8 weeks for fluoxetine) except for use of benzodiazepine or non-benzodiazepine sleeping agents
• Subject has a medical condition or disorder that:
• Is unstable and clinically significant, or:
• Could interfere with the accurate assessment of safety or efficacy of treatment, including:
• individuals who are using prescription drugs that may impair thermoregulatory cooling, including diuretics, barbiturates, and beta-blockers, or antihistamines,
• individuals with cardiovascular conditions or problems (uncontrolled hypertension, congestive heart failure, or documented evidence of coronary artery disease)
• individuals with chronic conditions/diseases associated with a reduced ability initiate thermoregulatory cooling, including Parkinson's, multiple sclerosis, central nervous system tumors, and diabetes with neuropathy,
• hemophiliacs/individuals prone to bleeding,
• individuals with a fever the day of study intervention,
• individuals with hypersensitivity to heat,

Sponsors & Collaborators

• University of Arizona: lead

Study Sites (1)

University of Arizona

Tucson, Arizona, 85724, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Magnetic Resonance Imaging; Electrocardiography; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Electrodiagnosis; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Charles Raison, MD

  University of Arizona, Department of Psychiatry, College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Department of Psychiatry (College of Medicine) and the Norton School of Family and Consumer Sciences

Study Record Dates

• First Submitted: February 7, 2014
• First Posted: February 14, 2014
• Study Start: February 1, 2014
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: August 10, 2015

Record last verified: 2015-08

Locations

US (1)