Whole Body Hyperthermia & Combat-Related Posttraumatic Stress Disorder (PTSD)

The investigators will direct a clinical trial of Whole Body Hyperthermia (WBH) for
treatment of PTSD related to combat exposure. Although the investigators have not yet
studied WBH for PTSD, the investigators have data indicating that WBH is effective for the
acute treatment of major depression (MDD). Given the high overlap of symptoms between PTSD
and Major Depressive Disorder (MDD), as well as the fact that most people with PTSD also
meet criteria for MDD, the investigators have reasons for expecting that WBH may also be of
benefit for PTSD. The primary objective of the proposed study is to determine if WBH
produces improvement in core PTSD symptoms, just as it appears to do in MDD. Indeed, in
preliminary studies, a single exposure to WBH resulted in a downward shift in body
temperature and a decrease in depressive symptoms as measured using the Center for
Epidemiologic Studies Depression Scale (known as the ADS in Germany where this study was
conducted) 5 days later. In addition, following exclusion of one patient with
bronchopulmonary inflammation that did not show a decrease in body temperature following
treatment, a correlation between the shift in body temperature and ΔADS approached
statistical significance. These preliminary data are consistent with previous studies
showing that 1) patients with seasonal affective disorder in winter during depression have
blunted thermoregulatory cooling but have thermoregulatory cooling that is similar in
efficiency to control subjects after successful antidepressant response to phototherapy (the
retina has direct projections to DRVL serotonergic neurons), 2) ECT increases the circadian
amplitude of core body temperature, and decreases mean core body temperature, particularly
during the nighttime thermoregulatory cooling period, and 3) thermoregulatory cooling, as
evidenced by the number of active sweat glands in depressed patients, increases upon
clinical recovery, but not earlier, following ECT. the investigators hypothesize that these
relationships in preliminary data and in previous studies are due to dysfunction of the
afferent signaling arm of the thermoregulatory system in MDD, specifically the warm afferent
system projecting to the LPB and, secondarily, to the DRVL/VLPAG and DRI subsets of
serotonergic neurons that have been implicated in anxiolytic and antidepressant actions,
respectively, and to normalization of warm afferent signaling following treatment. Again,
given the high degree of overlap between PTSD and MDD, the investigators expect that WBH may
confer therapeutic benefits in PTSD as it appears to do in MDD.

This clinical trial will only include individuals with PTSD (i.e. no normal controls) in
order to determine whether there is a significant effect of a single treatment with WBH
administered in an open manner on PTSD symptoms. Based on our data from patients with MDD,
the investigators expect that if WBH has an effect on PTSD symptoms, this will be apparent
immediately after the treatment and will persist for at least a week. Therefore, the
investigators will assess PTSD symptoms prior to and a week following a single treatment
with WBH.

Useful preliminary results were obtained from a pilot study comparing mildly to severely
depressed patients receiving hyperthermic treatment (N=11) to depressed patients receiving
psychotherapy as usual (N=3). Baseline scores on the German language ADS depression scale
were similar for the two groups (mean=30.64, sd=9.18, N=11, vs. mean =32.33, sd=17.04, N=3).
Raw change on the ADS was significantly greater for the hyperthermia group (mean=-11.91,
sd=6.55, N=11, vs. mean=-1.33, sd=4.51, N=3; t=2.60, df=12, P=0.023), resulting in a very
large standardized treatment difference (Cohen d) of 1.69 (95% CI=1.00 - 2.48). Percent
change was also significant (mean=-39.4, sd=18.9, N=11, vs. mean=-8.6, sd=17.0, N=3; t=2.54;
df=12, P=0.026), for a Cohen d of 1.66 (95% CI=0.93 - 2.39). The percentage of the
hyperthermia vs. psychotherapy group achieving a clinical response (>50% reduction from
baseline) was 27.3% vs. 0%, and the percentage achieving at least a partial response (>25%
improvement) was 81.8% vs. 33.3%. These data suggest that our proposed sample size of 10
individuals with combat-related PTSD should be sufficient to identify a potential
therapeutic effect, assuming that such an effect would be of similar magnitude to the effect
seen in MDD.

Inclusion Criteria:

- Male or female outpatients aged 18-65.

- Able to understand the nature of the study and able to provide written informed
consent prior to conduct of any study procedures.

- A diagnosis of combat-related PTSD based on a PTSD Checklist (PCL)-Military Version
score of 50 or greater and meets a diagnosis of PTSD by DSM-V criteria.

- In the investigator's opinion, has met DSM-V criteria for PTSD for at least 4 weeks
prior to signing consent.

- Able to communicate in English with study personnel.

- 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 per
self-report.

Exclusion Criteria:

- Any of the following diagnoses, as identified by the psychiatric evaluation or study
assessments:

- A current DSM-IV-TR Axis I diagnosis of Dementia; or

- Any current DSM-IV-TR Axis II diagnosis (i.e. personality disorder) that would
suggest potential noncompliance with the protocol; or

- A lifetime history of Schizophrenia, Schizoaffective Disorder, or a Bipolar Disorder
Type 1; or

- A diagnosis claustrophobia severe enough that it would impair ability to be in the
Heckel HT3000 hyperthermia device

- A current (or within 12 months prior to the Screening visit) diagnosis of Anorexia
Nervosa or Bulimia Nervosa

- Subject has met DSM-IV criteria for Substance Abuse in the month prior to screening
visit, or non-remitted Substance Dependence in the 2 weeks prior to screening visit.

- A diagnosis of an anxiety or mood disorder that is considered by the investigator to
be of greater source of distress or functional impairment than the patient's PTSD
diagnosis. Subjects with co-morbid anxiety and mood disorders not excluded above and
considered to be of secondary importance will be permitted in the study.

- Participation in concurrent formal psychotherapy during the trial, or in the 2 weeks
prior to the screening visit.

- 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 (if so, they will be
rescheduled),

- individuals with hypersensitivity to heat,

- individuals with recent acute joint injury (i.e. arthritis),

- individuals with enclosed infections, be they dental, in joints, or in any other
tissues,

- Clinically significant, in the investigator's opinion, abnormal findings on screening
laboratory tests or physical exam.

- Presence of clinically significant suicide risk, based on the investigator's opinion,
or a Columbia Suicide Severity Risk Scale (C-SSRS) suicidal ideation score of 4 or 5.
Any suicide attempt within 3 months of the Screening visit is exclusionary.

- Use of any psychotropic medications for 2 weeks (8 weeks for fluoxetine) prior to
initiation of the study, with the exception of a stable dosage of benzodiazepine or
non-benzodiazepine hypnotic medications (e.g. zolpidem (Ambien), zaleplon (Sonata),
eszopiclone (Lunesta), lorazepam (Ativan), diazepam (Valium), clonazepam (Klonopin),
alprazolam (Xanax),

- Need for any non-protocol psychotropic medication once enrolled, with the exception
of benzodiazepine or non-benzodiazepine hypnotics used at a stable dosage.

- Use of any psychoactive dietary or herbal products in the 2 weeks prior to screening
visit 2, or at any time during the trial.

- Women who are pregnant (HCG pregnancy test at screening) or lactating, or who plan to
become pregnant during the study.

- Current participation in any clinical trial that might impact results of this one,
which includes participation in another clinical trial for depression, as well as
drug trials with agents that might affect mood or regulation of body temperature.

- Reasonable likelihood for non-compliance with the protocol for any other reason, in
the opinion of the Investigator, prohibits enrollment of subject into the study.

- Obesity and overall size of subject. It will be at the PI's discretion to consider
BMI, waist circumference, and body fat composition when determining eligibility and
safety of the individual.

- History of peripheral circulatory disease, for example peripheral vascular disease,
deep vein thrombosis (DVT), or lymphedema.

- History of a cerebral vascular accident.

- History of stroke, epilepsy or cerebral aneurisms.

- Cancer in the last five years, except for fully resected non-melanoma skin cancer.

- Diabetes mellitus types I or II.

- Any clinically significant autoimmune disease (compensated hypothyroidism allowed).

- Active alcohol/drug abuse in 2 weeks prior to screening for those who have been
dependent or have abused on drugs/alcohol in the last 2 months.