Stellate Ganglion Blockade in Post-Menopausal Women

Scope:

Post-menopausal women with moderate to severe VMS will be enrolled as participants in this
study.

Specific Goals and Objectives:

Primary Objective

1. To determine the effect of SGB for reducing frequency and intensity of menopausal VMS.

Hypothesis 1a. Seven-day mean frequency of VMS will be lower in women randomized to
active SGB compared to sham control.

Hypothesis 1b. Seven-day mean intensity of VMS will be lower in women randomized to
active SGB compared to sham control.

Hypothesis 1c. The VMS Intensity (Frequency*Severity), will be lower in women randomized
to active SGB compared to sham control.

Secondary Objectives

2. To evaluate the effect of SGB on VMS Intensity, objective VMS, mood, memory, and sleep
quality.

Hypothesis 2a The frequency of objectively measured VMS will be lower in women
randomized to active SGB compared to sham control.

Hypothesis 2b. Depressive symptoms and memory, but not sleep quality, will improve more
in women randomized to active SGB compared to sham control.

Hypothesis 2c. The magnitude of improvements in memory will relate to the magnitude of
reduction in VMS, even after controlling for sleep.

3. To probe the mechanisms by which SGB improves VMS.

Hypothesis 3a. In a nested sub study, neuroimaging assessments will reveal that compared to
sham control, active SGB is associated with a) decreased functional connectivity in the
default mode network during the resting state, particularly for networks supporting the
insula and hippocampus; b) reduced activation in the hippocampus, dorsolateral prefrontal
cortex, and anterior cingulate during a verbal memory task; and c) reduced activation in the
amygdala during an emotion processing task.

Hypothesis 3b. Compared to sham control, SGB will immediately diminish ipsilateral stellate
ganglion nerve activity and sympathetic tone as measured by skin sympathetic nerve monitoring
(SKNA) and these effects will be reassessed at 2 and 4 weeks after the intervention to assess
if effects of SGB on stellate ganglion activity are long lasting.

Inclusion Criteria:

1. post-menopausal woman defined according to the following criteria: 12 months of
spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels ≥
40 IU/ml or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy

2. aged 40 to 65 years

3. 50 or more reported moderate-to-severe hot flashes per week

4. a minimum of two weeks of VMS diary recording prior to SGB

5. post-menopausal women whose vasomotor symptoms are refractory to approved oral
treatments (i.e., hormone therapy or paroxetine) or for whom hormone therapy is
contraindicated or for women who refuse any oral therapy

6. willingness to undergo fluoroscopy-guided SGB or sham treatment.

7. safety labs within 30 days of SGB intervention

Exclusion Criteria:

1. conditions that preclude SGB or sham intervention (e.g., anatomic abnormalities of the
anterior neck or cervical spine ; goiter, cardiac/pulmonary compromise; contralateral
(left-sided) phrenic nerve paralysis or diaphragmatic paresis; history of seizure,
coma, or stroke; history of neurologic deficit to the brachial plexus or an abnormal
brachial plexus neurologic exam; history of Zenker's diverticulum; acute
illness/infection; coagulopathy or bleeding abnormalities; INR >1.3; hemoglobin<9.0,
platelets <100,000, BUN ≥ 30mg/dl; creatinine ≥ 2 mg/ml; ALT (SGPT), AST (SGOT), Alk
Phos ≥ three times the upper limit of normal; serum potassium (K+) ≤ 3.5 or ≥ 5.0
mEq/L allergic reactions or contraindications to a local anesthetic or contrast dye,
systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg,
pregnancy

2. If LMP is between 6 to 12 months, FSH < 40

3. use of treatments less than the washout period and throughout study participation that
can affect VMS frequency or severity, including oral (2 months) or transdermal hormone
therapy(1 month), botanicals (e.g., soy, red clover, black cohosh, etc.)(1 month),
oral contraceptives(2 months), serotonin selective reuptake inhibitors (SSRI) (2
weeks), serotonin norepinephrine reuptake inhibitors (SNRI),( 2 weeks) gabapentin,
pregabalin, clonidine, selective estrogen receptor modulators, aromatase inhibitors,
tissue selective estrogen complexes;(2months)

4. use of aspirin and non-steroidal anti-inflammatory medications for 3 days prior to the
SGB procedure; all other anti-platelet or anticoagulation medications will be
discontinued with the permission of the participant's prescribing physician

5. for cognition testing: conditions or disorders that can affect performance on
cognitive tests (e.g., dementia/mild cognitive impairment, Mini-Mental State Exam
(MMSE) less than or equal to 27) at baseline; stroke; traumatic brain injury;
alcohol/substance use; inability to write, speak, or read in English, English as a
second language, participation in other studies involving tests of cognitive
abilities,

6. conditions that can affect depressive symptoms (e.g., current diagnosis of major
depression, bipolar disorder, or other Axis I Psychiatric disorder); Personal Health
Questionnaire Depression Scale (PHQ-8)> 15

7. Exclusion criteria for neuroimaging study: implantable pulse generators for
pacemakers, defibrillator devices and most but not all spinal cord stimulators or deep
brain stimulator, ferrous-containing metals within the body (e.g., braces, aneurysm
clips, shrapnel/retained particles) inability to tolerate small, enclosed spaces
without anxiety (e.g. claustrophobia), weight > 300 lbs. unless height is sufficiently
high [e.g., + 5'11"] so that waist and shoulder circumference do not prevent her from
fitting in the scanner; opted out of cognition study, shift work

8. Exclusion criteria for SKNA study only allergic to adhesive in electrode