Pill Study Hyperthermia Device (Heckel HT 3000): Monitoring Core Body Temperature Using Wireless Technology

This protocol will allow for the evaluation of a wireless measuring device for core body
temperature and a comparison to the data taken with a rectal thermometer, during a Whole
Body Hyperthermia (WBH) in various subject populations. The primary objective of the
proposed study is a potential change from wired core body temperature measurement with a
rectal thermometer to an indigestible thermometer with wireless technology.

The recent standard for measuring core body temperature during WBH procedures is the use of
an indwelling rectal thermometer to constantly monitor the temperature for safety and for
research reasons. Experiences from different clinics and research groups, including ours,
show a high drop-out rate of potential study participants and patients, because of the
discomfort of self-inserting a rectal thermometer for the treatment in a Whole-Body
Hyperthermia. A wireless and reliable measuring technology would open this treatment for
participants, who are declining their participation due to the indwelling thermometer. This
device will exit the subject's body via bowel movement 1-5 days following ingestion and will
not be reused.

Due to the proximity of the indwelling thermometer to the surface of the body, the
temperature does not reflect the real core body temperature and preliminary data, taking by
our group, suggest a significant, but stable difference between core body temperatures
measured with an indigestible device, compared to the temperature taken with the rectal
probe. WBH treatments, currently studied by our group at the University of Arizona, are of
mild nature and the constant infra-red heating is stopped, as soon as a patient reaches the
rectal temperature of 38.5 C. Due to the fact, that the bodies surface is heated up through
the infrared exposure, the investigators assume, that the core body temperature will be
lower, compared to the rectal temperature. A validation study in 20 subjects therefore is
necessary to determine the differences in the measuring methods. This is especially
important, as the end-point of the treatments is defined by the core body temperature, and
different endpoints by switching from one measuring method to the other, without validation,
would potentially bias the study results.

Receiving a treatment in the WBH machine is of non-significant risk and can be compared to
e.g. a sauna visit or an intense exercise, in terms of the physiological reaction. It is
currently studied by our group for the treatment of Major Depressive Disorder, PTSD and
other chronic illnesses. This trial however will not be limited to only include individuals
with MDD or PTSD, but will allow for an expanded use in all populations (while still
excluding subjects based on safety parameters). The investigators will monitor subject's
physiological and clinical outcomes (if applicable) from a single Whole Body Hyperthermia
treatment in an open fashion (no placebo/control condition). This study will include safety
assessments several days prior to or same day as the WBH, and include follow-up assessments
1 day and 1 week later.

Inclusion Criteria:

- Male or females aged 18-50 years.

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

- Able to communicate in English with study personnel.

- For women of child-bearing potential (i.e., one who is biologically capable of become
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 6 months prior to the Screening visit) diagnosis of Anorexia
Nervosa or Bulimia Nervosa

- Individuals with psychiatric diagnoses may be excluded per the investigator's
discretion.

- If patient has a medical condition or disorder that:

- Is unstable and clinically significant, or:

- Could, in the investigator's opinion, interfere with the accurate assessment of
safety or efficacy of the procedure, including:

1. individuals who are using prescription drugs that may impair thermoregulatory
cooling,

2. individuals with cardiovascular conditions or problems (uncontrolled
hypertension, congestive heart failure, or documented evidence of coronary
artery disease)

3. 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,

4. individuals with a fever the day of study intervention (if so, they will be
rescheduled),

5. individuals with hypersensitivity to heat,

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

- 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),

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

- 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 up to the PI's discretion will
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 and
fibromyalgia 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 (with the exception of
marijuana use).

- Individuals with a history of having difficulty swallowing food or large capsules
will be excluded from participating in the assessment of core body temperature
(because swallowing a large sensor pill is required). The indigestible temperature
capsules will not be used in subjects with any known or suspected obstructive disease
of the gastrointestinal tract including, but not limited to esophageal stricture,
diverticulosis and inflammatory bowel disease (IBD), peptic ulcer disease, Crohn's
disease, ulcerative colitis; previous gastrointestinal surgery.

- Individuals who have experience with cognitive enhancing programs such as Luminosity,
Cogmed or Elevate.