A Mind-Body Intervention for Hot Flash Management

This randomized, two arm clinical trial will evaluate the efficacy of self-administered
hypnosis for the treatment of hot flashes in postmenopausal women using a 1:1 randomization
schedule.

Primary Objective

To evaluate the efficacy of the self-administered hypnosis intervention for hot flashes
compared to the self-administered white noise hypnosis.

Hypothesis 1: Self-administered hypnosis will significantly decrease vasomotor symptoms (hot
flash score of frequency and severity) compared to the self-administered white noise hypnosis
at 6 weeks.

Secondary Objectives

To evaluate the efficacy of the self-administered hypnosis compared to self-administered
white noise hypnosis for hot flash activity interference, sleep disturbance, anxiety and
perception of benefit; with the expectation that there will be significant improvements among
participants in the self-administered hypnosis group when compared with the self-administered
white noise hypnosis group at 6 weeks. The investigators will also evaluate the effects of
self-administered hypnosis compared to the self-administered white noise hypnosis at 12 weeks
for all secondary outcomes except perception of benefit. Additionally, mediators (perceived
stress, cortisol, and heart rate variability (HRV)) and moderators (hypnotizability and
practice adherence) of hot flash reduction will be explored.

Hypothesis 2.1: Compared to self-administered white noise hypnosis, the self-administered
hypnosis intervention will result in significant improvements in hot flash activity
interference, sleep disturbance, and anxiety at 6 and 12 weeks, and perception of benefit at
6 weeks.

Hypothesis 2.2 A decrease in perceived stress will be indicated in the self-administered
hypnosis group due to the intervention, which will correspond and contribute to further
decrease of the hot flash score at 6 and 12 weeks.

Hypothesis 2.3 Diurnal salivary cortisol will demonstrate better circadian rhythms (steeper
slopes) in those with larger hot flash reductions and in the self-administered hypnosis group
compared to participants in the self-administered white noise hypnosis at 6 weeks.

Hypothesis 2.4 Self-administration of hypnosis and greater hot flash reductions will result
in higher resting and 24-hour parasympathetic activity, reflected as higher HRV at 6 weeks.

Hypothesis 2.5 Higher hypnotizability scores and better adherence rates will be associated
with greater reductions in hot flash scores in the self-administered hypnosis group.

Hypothesis 2.6 Self-administered hypnosis will significantly decrease vasomotor symptoms (hot
flash score of frequency and severity) compared to the self-administered white noise hypnosis
at 12 weeks.

Recruitment Plan

Potential participants will be identified in three ways: postcard mailings and invitation
letters; physician referrals and IRB approved chart screening; and flyers, advertisements and
press releases. Physician referrals will come primarily from cancer centers at University of
Michigan Cancer Center Breast Clinic in Ann Arbor, MI, and the Baylor Scott & White Health
Center in Waco, TX.

At Michigan, key eligibility criteria will be used to identify potential eligible women
through the Honest Broker Office. Charts will be further screened, with IRB approval, for
eligibility. If eligible, women will be sent an invitation letter where they can opt in or
out of being contacted to learn more about the study.

In addition, at Michigan, outreach will occur through obstetrics and gynecology, mammography,
and internal medicine clinics to enable recruitment of women without a history of breast
cancer. Mass mailings and local advertisement may also be used.

At Baylor University, a successful and proven method of accrual has been the use of mass
mailings and local advertisement (e.g. newspaper, magazines, flyers). Additionally, Dr.
Elkins is a medical associate with Baylor Scott & White Health Center, which provides a
direct connection with physicians and medical staff who will provide potential referrals.

It is expected that each site (Baylor University and University of Michigan) will recruit
approximately half of the participants. Accrual will be closely monitored and efforts to
randomize an equal number at each site will be made.

The study coordinators will provide education about the trial and a consent form for review
both by phone and at the baseline/consent session. All other education beyond the baseline
data collection will be provided at the second session 7-30 days later. Both sessions will be
between 45-60 minutes. Sessions will be held at Dr. Barton's and Dr. Elkin's research
offices, which each provide privacy, a recliner, a relaxing environment, and convenient
parking.

Inclusion Criteria:

Postmenopausal as defined by one of the following criteria:

- No menstrual period in the past 12 months

- Chemical menopause (LHRH antagonists)

- Surgical Menopause (bilateral oophorectomy)

- Evidence of menopause status per FSH and estradiol levels per institutional
guidelines. Self-reported history of a minimum of 4 hot flashes per day or 28 hot
flashes per week at baseline.

Age over 18 years and able to give consent for participation in the study.

Have discontinued other putative therapies for hot flashes for at least one month prior to
enrollment (Vitamin E will be allowed)

Women with a diagnosis of DCIS or invasive breast cancer stages 0-III are allowed to
participate and may be on endocrine therapy of any kind. If on endocrine therapy, women
must be on it for 4 weeks and not expected to stop it during the study. If not on endocrine
therapy, participants should not be planning to start during the course of the study.
However, unexpected treatment will not require study withdrawal but will be recorded and
considered in the analysis.

Exclusion Criteria:

- Currently receiving other simultaneous treatment for hot flashes (antidepressant use
is allowed if being used for mood alterations and participant has been on the
antidepressant for at least 3 months with no plans to change dose or antidepressant
during this study)

- Diagnosis of clinical depression or acute anxiety disorder

- Currently using any Complementary and Alternative Medicine (CAM) treatments for
vasomotor symptoms. (This would include soy products and other phytoestrogens, black
cohosh, and any mind-body techniques including meditation, yoga, etc.). If any
therapies are used for reasons other than hot flashes and hot flash frequency meets
inclusion criteria, then woman is eligible)

- Diagnosis of a serious psychological illness, specifically psychoses, schizophrenia or
borderline personality disorder

- Currently using hypnosis for any reason

- PHQ-4 score ≥ 9

- Non-English speaking

- Women with stage IV breast cancer