Clinical trial NCT03122301
Conditions: Hot Flashes Hot Flushes Vasomotor Symptoms
Sponsor: Northwestern University
Start date: 2017-06-01; Completion date: 2020-07-01
Enrollment: 2 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Vasomotor symptoms (hot flashes, night sweats, VMS) affect up to 65% of breast cancer survivors and negatively impact their quality of life. VMS in Hispanic women are significantly more severe as compared to non-Hispanic Caucasian women. Few effective treatments for VMS are available, especially in the underserved Hispanic and Spanish-speaking populations which is problematic, as Hispanics will comprise 20% of the U.S. population by 2025. Stellate ganglion nerve block (SGB) with local anesthetic, previously performed for chronic pain indications, has shown promise as a potential treatment for menopausal women with VMS in previous clinical trials, but has not been investigated in Hispanic or Spanish-Speaking women with breast cancer in a controlled study.

Detailed description:
In this study, investigators aim to assess the effects of SGB on VMS, sympathetic nervous system activity, depression and sleep in Hispanic and Spanish-Speaking women with breast cancer on endocrine therapy who take tamoxifen, aromatase inhibitors (AIs) or SERMS, in a prospective, randomized, sham-controlled pilot study.

Project Hypothesis: The frequency and intensity of subjective and objective VMS will be significantly lower in women randomized to active SGB as compared to sham control.

Project Scope: Hispanic and Spanish-speaking women with breast cancer on tamoxifen, aromatase inhibitors or SERMs with moderate to severe VMS will be enrolled as participants in this study. Eligible women will be specifically recruited from the oncology practice of Dr. Cesar Santa Maria, as well as Northwestern Memorial Hospital and other Northwestern affiliates.

Specific Goals and Objectives:

Goal 1: Determine the effect of stellate ganglion blockade (SGB) for reducing subjective and objective VMS in Hispanic women with breast cancer on endocrine therapy as this population is known to have a greater severity of VMS and has been notoriously underserved and understudied in the U.S. and in clinical trials.

Goal 2: Evaluate the effect of SGB on the sympathetic nervous system over time to gain new knowledge on the physiologic mechanism of SGB effects on VMS.

Goal 3: Evaluate the effect of SGB on mood, sleep, and quality of life in women with breast cancer on tamoxifen, AIs, or SERMs.

Goal 4: Using the results of this pilot study, investigators plan to submit an R01 grant to the National Cancer Institute in 2017 for a larger scale study.

Arms: arm 1: Stellate Ganglion Block Injection with bupivicaine arm 2: Saline injection
Interventions: intervention 1: Stellate Ganglion Block injection with bupivicaine intervention 2: Saline
Intervention descriptions: intervention 1: A computer-generated 1:1 block randomization scheme will be used to assign participants to receive either a SGB with bupivacaine or a sham injection with saline. Randomization will be performed by the injectionist immediately before the injection procedure by opening an opaque envelope to reveal the participant number and group assignment printed on an index card. intervention 2: sham injection with saline

Protocol documents:
Prot_SAP_000.pdf: 
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PROTOCOL TITLE: 
Effects of Stellate Ganglion Block on Hot Flashes in Hispanic Women with Breast 
Cancer: A Pilot Randomized Sham – Controlled Trial  
PRINCIPAL INVESTIGATOR: 
David Walega, MD, MSCI 
Department of Anesthesiology 
Northwestern University Feinberg School of Medicine 
312-926-9142 
d-walega@northwestern.edu 
 
VERSION NUMBER: 1 
VERSION DATE: January 5, 2017 
 


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Table of Contents 
1.0 
Objectives ................................................................................................................ 3 
2.0 
Background .............................................................................................................. 4 
3.0 
Inclusion and Exclusion Criteria .............................................................................. 6 
4.0 
Study-Wide Number of Subjects ............................................................................. 7 
5.0 
Study-Wide Recruitment Methods .......................................................................... 7 
6.0 
Multi-Site Research ................................................................................................. 8 
7.0 
Study Timelines ....................................................................................................... 8 
8.0 
Study Endpoints ....................................................................................................... 8 
9.0 
Procedures Involved ................................................................................................. 9 
10.0 Data and Specimen Banking .................................................................................. 14 
11.0 Data and Specimen Management ........................................................................... 14 
12.0 Provisions to Monitor the Data to Ensure the Safety of Subjects .......................... 17 
13.0 Withdrawal of Subjects* ........................................................................................ 18 
14.0 Risks to Subjects* .................................................................................................. 19 
15.0 Potential Benefits to Subjects ................................................................................ 21 
16.0 Vulnerable Populations .......................................................................................... 21 
17.0 Community-Based Participatory Research ............................................................ 21 
18.0 Sharing of Results with Subjects ........................................................................... 21 
19.0 Setting .................................................................................................................... 21 
20.0 Resources Available ............................................................................................... 21 
21.0 Prior Approvals ...................................................................................................... 23 
22.0 Recruitment Methods ............................................................................................. 23 
23.0 Local Number of Subjects ..................................................................................... 24 
24.0 Confidentiality ....................................................................................................... 24 
25.0 Provisions to Protect the Privacy Interests of Subjects .......................................... 25 
26.0 Compensation for Research-Related Injury ........................................................... 26 
27.0 Economic Burden to Subjects ................................................................................ 26 
28.0 Consent Process ..................................................................................................... 26 
29.0 Process to Document Consent in Writing .............................................................. 27 
30.0 Drugs or Devices.................................................................................................... 27 
 


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1.0 
Objectives 
  
1.1 
Research Aims: 
 
Breast cancer and the common vasomotor symptom side effects (hot flashes, night 
sweats, VMS) of cancer treatment affect a large number of women from all age 
demographics and ethnicities in the U.S.   Vasomotor symptoms (VMS) affect up 
to 80% of breast cancer survivors and negatively impact their quality of life.   
Studies have shown that Hispanic women report more severe VMS as compared 
to Caucasian women. Very few effective treatments are available for VMS, and 
racial, ethnic, and socioeconomic disparities significantly decrease access to 
treatments that are available. Hispanic, non-English speaking patients are 
typically excluded from clinical trials which test these treatments because of 
increased costs of translation limitations of validated outcome measures and 
instruments for this population and non-Spanish speaking research teams. In fact, 
in the recent Study of Women's Health Across the Nation (SWAN) study, a large 
multicenter study of VMS in over 3300 participants, only 7.5% of participants 
were Hispanic, despite a much higher percentage of Hispanics in the U.S.  
 
As breast cancer survivorship becomes the norm with improved detection and 
treatment, attention to breast cancer survivorship issues in all women regardless 
of race or ethnicity, particularly the long lasting effects of chemotherapy and 
endocrine therapy are paramount. 
 
Stellate ganglion blockade (SGB) with local anesthetic, previously performed for 
chronic pain indications, has shown promise as a treatment for women with VMS 
in previous clinical trials, but has not been investigated in women with breast 
cancer receiving anti-estrogen therapy, nor specifically studied in Hispanic 
women. 
 
We aim to address this disparity in the study of SGB efficacy and evaluate the 
benefit of SGB specifically in symptomatic Hispanic women with breast cancer 
seeking relief from moderate to very severe VMS, using outcome measures 
validated in both Spanish and English. 
 
 
Scope:  Hispanic and Spanish speaking women with breast cancer on Tamoxifen, 
aromatase inhibitors, SERMs or other similar endocrine therapy with moderate to 
very severe VMS will be enrolled as participants in this study.   
 
Hypotheses:   
 
The frequency and intensity of subjective and objective VMS will be significantly 
lower in women randomized to active SGB as compared to sham controls. The 
sympathetic nervous system tone will be diminished in the treatment group as 
compared to the sham-control group and sleep, and quality of life will be 
improved in the treatment group as compared to the sham-control group. 


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Specific Goals and Objectives:   
 
Goal 1: Determine the effect of stellate ganglion blockade (SGB) for reducing subjective 
and objective VMS in Hispanic women with breast cancer on endocrine therapy 
(tamoxifen, aromatase inhibitors, SERMs) as this population is known to have a 
greater severity of VMS and negative QOL from these symptoms, and has been 
notoriously underserved and understudied in clinical trials.                          
                                                                
Goal 2: Evaluate the effect of SGB on the sympathetic nervous system over time to gain 
new knowledge on the physiologic mechanism of SGB effects on VMS.  
 
Goal 3: Evaluate the effect of SGB on mood, and quality of life in these women with 
breast cancer using measures that have been previously validated in this 
population. 
 
 
2.0 
Background 
 
VMS (hot flashes and night sweats) are common in women with breast cancer in 
those treated with tamoxifen, aromatase inhibitors, selective estrogen receptor 
modulators (SERMs) and other chemotherapy. To many of these women, these 
symptoms are severe and intolerable, with a significant decrease in quality of life.  
VMS are also more common in African American and Hispanic women, and although 
the incidence of breast cancer is lower in Hispanic women as compared to Caucasian 
women, disease severity is greater, necessitating aggressive or prolonged treatment, 
including endocrine therapy.  Importantly, VMS may be a factor in premature 
discontinuation of endocrine therapy for all women with breast cancer, though 
underserved and understudied minority populations may be at greater risk. 
 
 
2.1 
  
Describe any relevant preliminary data. 
 
 
Uncontrolled studies of women with breast cancer and heterogeneous populations 
including menopausal women have demonstrated improvements in the frequency and 
intensity of VMS following stellate ganglion blockade (SGB) with local anesthetic, 
with effects ranging from 45-90% reduction for 6 weeks to several months. These 
same studies showed improvements in sleep quality as well.   
 
 
The stellate ganglion is a neural structure in the anterior cervical spine region and is 
part of the sympathetic nervous system.  It has been injected safely in the practice of 
pain management for more than 50 years in cases of post herpetic neuralgia 
(shingles), complex regional pain syndrome (CRPS) and other painful neuropathies 
and is an emerging treatment for some cardiac dysrhythmias. Prior studies have 


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confirmed anatomic connections between the stellate ganglion and the insular cortex 
and hypothalamus via third order neurons. 
 
2.2 
Describe the relevant prior experience and gaps in current 
knowledge 
We recently published a prospective, randomized, sham controlled study of SGB in 
women with natural or surgical menopause, in which we found a 52% decrease in 
moderate to very severe VMS in women who underwent a single SGB with 
bupivacaine, a local anesthetic, as compared to a 4% decrease in women in the sham 
control group who underwent an injection of saline. We also identified statistically 
significant improvements in objective hot flashes and trends toward improved 
depression in the SGB treatment group, whereas such beneficial effects were not seen 
in the sham control group.  
 
 
Only one controlled study of SGB in women with breast cancer has been published to 
our knowledge. Patients with at least one month of VMS underwent either an image-
guided stellate ganglion injection at the C7 level with 0.5% bupivacaine 10mL, or, 
were prescribed pregabalin, a membrane stabilizer found to diminish vasomotor 
symptom in some patients, at 75 mg twice daily; patients were followed for 3 months. 
Participants recorded the intensity and frequency of hot flashes in a diary. Both 
treatment groups were observed to have considerable reductions in frequency and 
intensity of VMS, but there was no control group in the study design, the 
randomization method was not described, and participants were not blinded to their 
treatment.  As it is well known that the placebo effect in hot flash studies can be 
dramatically high, more than 60% in some reports, it is important to use a study 
design that evaluates the placebo effect of any treatment.   
 
 
As eligibility for most of these VMS trials included English fluency, Spanish-
speaking women have been excluded from participation to date.  In fact, only 10% of 
participants in our prior RCT were Hispanic and there was even less Hispanic 
representation in the SWAN study of over 3,300 women in the U.S. 
   
 
Our prior work demonstrated a significant treatment effect with SGB for VMS in 
women with natural or surgical menopause. In addition to the fact that VMS are 
typically more severe and bothersome in breast cancer patients and Hispanic women 
in particular, VMS symptoms can be a factor in patients stopping endocrine therapy 
as a breast cancer treatment. To date, no placebo controlled studies of SGB for VMS 
in Hispanic and Spanish-speaking women with breast cancer have been done.  
 
Provide the scientific or scholarly background for, rationale for, and significance of 
the research based on the existing literature and how will it add to existing 
knowledge 
Very few effective treatments are available for VMS, and racial and socioeconomic 
disparities significantly decrease access to treatments that are available. Although 
hormone therapy (HT) remains a highly effective treatment for VMS in some 


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menopausal women, HT is contraindicated in breast cancer patients, breast cancer 
survivors, and those at risk of breast cancer or other hormone sensitive malignancies.   
 
Non pharmacologic treatments like botanicals, acupuncture, yoga, and lifestyle 
interventions have shown little to no improvements in VMS symptoms in clinical 
trials. Although Brisdalle (Paroxetine, an SSRI anti-depressant) was approved by the 
FDA in 2013 as the only approved non-hormonal treatment of VMS in menopausal 
women, SSRIs may inhibit tamoxifen hepatic metabolism and therefore its use is 
controversial in the breast cancer population.  
 
 
 
The exact mechanism of SGB is not fully understood. Treatment with SGB is based 
on the interruption of the sympathetic nervous system, changes in blood flow and 
modulation of norepinephrine (NE) levels or nerve growth factor (NGF) in the 
thermoregulatory regions of the brain. As well, remodeling or modulation of neural 
receptor systems or feedback systems involving the stellate ganglion and the insular 
cortex, the thermoregulation and homeostatic control centers in the brain  may be 
affected. 
   
 
3.0 
Inclusion and Exclusion Criteria 
3.1 Describe how individuals will be screened for eligibility. 
 
 
Patient entry, exclusion and dropout criteria: 
a. General inclusion criteria include 
1. Hispanic or Spanish speaking women aged 30 to 70 years 
2. 28 or more reported moderate-to-very severe hot flashes 
per week  
3. a minimum of two weeks of VMS diary recording prior to 
SGB 
4. current use of tamoxifen, aromatase inhibitors, or SERMs 
for a breast cancer indication for at last six months  
5. willingness to undergo fluoroscopy-guided SGB or sham 
treatment.  
6. if participant is on an SSRI,SNRI or membrane stabilizer 
(pregabalin, gabapentin, for example), it must be a  
stable, unchanged dose for previous 3 months 
             
 
b. General exclusion criteria include:  
1. conditions that preclude SGB or sham intervention (e.g., 
anatomic abnormalities of the anterior neck or cervical 
spine; goiter, cardiac/pulmonary compromise; acute 
illness/infection; coagulopathy or bleeding disorder; 
allergic reactions/contraindications to a local anesthetic or 
contrast dye); pregnancy 
2. use of treatments in the past 2 months that can affect VMS 


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(e.g., use of oral or transdermal HT or contraceptives,  
 
3.2 
Describe the criteria that define who will be included or excluded 
in your final study sample. 
Participants will be interviewed in English or Spanish based on their preference, and all 
study materials including instructions, outcome measures, and consent forms will be 
available to participants in English and Spanish.  
 
After participants have reviewed and signed the consent form in person, they will be 
interviewed to determine candidacy for the study. They will be asked to provide 
information about themselves and their medical history. Before the intervention 
procedure, they will be asked to maintain a diary of VMS.  
 
Participants will be instructed to record the frequency and severity of each hot flash or 
night sweat using the following definitions which will be available in English and in 
Spanish: “mild” (< 5 minutes, warm, red face, uncomfortable), “moderate” (< 15 
minutes, warmth involving neck, ears, head, whole body, with perspiration, clammy skin, 
dry mouth, tense muscles, tachycardia, irritation, agitation, embarrassment), “severe” (< 
20 minutes, warmth described as a raging furnace or burning up, weak, faint, headache, 
chest heaviness, extreme perspiration, prickling sensation over skin, heart irregularities, 
anxious, panic attacks) or “very severe” (< 45 minutes, boiling eruption, rolling 
perspiration, inability to breathe, faint/dizzy, leg/foot cramps, heart irregularities, 
difficulty functioning, distressed, nausea). They will be asked to do this for a minimum of 
two weeks prior to the procedure in order to determine eligibility for the study. VMS 
eligibility will be re-assessed 24 hours before the SGB. A participant will not be 
permitted to proceed with the initial procedure if they do not have the completed written 
baseline diary for a confirmatory VMS frequency and severity count at the time of the 
procedure. 
 
3.3 Indicate specifically whether you will include or exclude each of 
the following special populations: 
The following special populations will not be included in this 
research: 
• 
Adults unable to consent 
• 
Individuals who are not yet adults (infants, children, teenagers) 
• 
Pregnant women 
• 
Prisoners 
 
4.0 
Study-Wide Number of Subjects-NA 
 
5.0 
Study-Wide Recruitment Methods-NA 
 


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6.0 
Multi-Site Research-NA 
 
7.0 
Study Timelines 
7.1The duration of an individual subject’s participation in the study 
Subjects will participate in this research study for seven months.  
             
              7.2 The duration anticipated to enroll all study subjects 
We expect to complete enrollment within twelve months. 
 
    
   7.3 The estimated date for the investigators to complete this study  
We expect to complete the study in approximately 1.5 years. 
 
8.0 
Study Endpoints 
8.1 Describe the primary and secondary study endpoints. 
Primary Outcome/Endpoint:  
Reduction in frequency and intensity of VMS subjective hot flashes that have been 
recorded on a paper diary for the duration of the study. 
   
Secondary outcomes/endpoint:  
Changes in the following measures from baseline, 3 months, 6 months: 
Objective hot flashes as measured over a 24-hour period with a validated skin        
conductance monitor 
Mood: Hot Flash Related Daily Interference Scale (HFRDIS) 
QOL: Functional Assessment of Cancer Therapy-Breast (FACT-B), Patient Global 
Impression of Change (PGIC), Post-Injection Questionnaire  
Sleep: Actigraphy changes in sleep quality over a 24 hour period  
 
In addition, Sympathetic Nerve Activity Monitoring (SKNA) using a non-invasive 
transcutaneous monitor for 90 minutes  prior to, during, and 90 minutes after the injection 
procedure; repeat monitoring will be performed again 2 and 4 weeks after the injection 
treatment. 
8.2 Describe any primary or secondary safety endpoints 
Participants will be NPO for the procedure. Before the procedure, a 22 or 20 g peripheral 
intravenous catheter (a plastic tube to take blood and give medicines without having to 
stick the vein multiple times) will be placed in the arm. An oxygen monitor and blood 
pressure cuff will also be placed before the procedure starts. Subjects will be positioned on 
their back on a procedure table in a fluoroscopy suite for this procedure. Their neck will be 
swabbed with disinfectant to clean the skin, the injection site will be draped in a sterile 
manner and sterile equipment and technique will be used for the entire of the procedure. 
 
After the study procedure is completed, subjects will stay in the office for half an hour for 
observation. Heart rate and pulse oximetry will be measured continuously and blood 
pressure will be checked every 5 minutes during the injection procedure and in the post 
injection observation phase.  Fluoroscopy times will be recorded.  Temperature 


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monitoring of the arm and hand, and clinical evaluation for temporary drooping of the 
right eyelid, redness in the eye, congestion in the nose, and sweating on the right side of 
the face will be performed.  These confirmatory signs of proper SGB placement will not 
be recorded as AEs.  
 
The study team will meet and review all adverse events after five subjects have been 
randomized and received the SGB procedure or sham. Per NU IRB protocol, all 
UPIRSO's or PRNCs will be reported a soon as the PI becomes aware of it. As the PI is 
the injectionist, the likelihood of missing a UPIRSO is highly unlikely. If no 
SAEs/UPIRSO's are observed, the team will meet again after 5 subjects have been 
randomized. No UPIRSOs or SAEs have occurred in previous studies.  
  
9.0 
Procedures Involved 
9.1  Describe and explain the study design. 
We aim to conduct a randomized, single-site, sham-control clinical trial of SGB on VMS 
in 20 Hispanic or Spanish-speaking women with breast cancer on anti-estrogen therapy 
(10 per group). The primary entry criterion will be 28 or more moderate to very severe 
hot flashes per week. VMS will be measured by self-report on a written daily dairy over a 
6-month period. Secondary outcomes include changes in mood, sleep, quality of life, , 
objective hot flashes measured by ambulatory monitoring (skin-conductance temperature 
monitoring) for 24 hours at baseline, three months and six months, and sympathetic 
nervous system tone before, during, immediately following and again 2 weeks and 3 
months after the injection procedure. 
 
Randomization and Masking Procedures A computer-generated 1:1 block randomization 
scheme will be used to assign participants to receive either a SGB with bupivacaine or a 
sham injection with saline. Randomization will be performed by the injectionist 
immediately before the injection procedure by opening an opaque envelope to reveal the 
participant number and group assignment printed on an index card. Randomization 
assignment will be kept under lock and key. Participants and all other study personnel, 
including those who will perform follow-up evaluations, will be blinded to group 
assignment. The injectionist will not have access to the written VMS diaries or any other 
secondary outcomes data until the conclusion of the study. 
 
9.2 
Provide a description of all research procedures being performed and when 
they are performed, including procedures being performed to monitor subjects for 
safety or minimize risks. 
 
Screening Visit 1 
 
Recording of Hot Flashes 
 
After the participant has reviewed and signed the consent form, they will be interviewed 
to determine if they are a candidate for the study. We will ask them to provide 
information about themselves and their medical history. Before having the SGB 


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procedure participants will be asked to maintain a daily paper diary of their hot flashes, 
recording the number and severity using a scale that will be provided to them in English 
and Spanish. They may choose to fill out the diaries in either language. They will be 
asked to do this a minimum of two weeks prior to the SGB procedure in order to 
determine if they are eligible for the study. They will also record any comments about the 
hot flashes they experience each day.  
 
At the end of two weeks, a member of the study team will telephone to ask how many hot 
flashes they are experiencing in a week. If they qualify based on the total number of hot 
flashes, they will be scheduled to return to the research office for placement of the hot 
flash monitor, actigraph watch and questionnaire completion.  
 
The study procedure with Dr. David Walega in the Department of Anesthesiology will be 
scheduled to occur at a separate visit. 
 
Visit 2 (2 to 3 weeks after visit 1)   
 
There are 4 types of research evaluations that they will be asked to complete: 
questionnaires, hot flash monitoring, actigraph watch monitoring and sympathetic 
nervous system activity monitoring.  
They will be asked to complete questionnaires, hot flash monitoring and actigraph watch 
monitoring at three time points: before the procedure, three months after the procedure, 
and six months after the procedure.  
Sympathetic nervous system activity monitoring will be performed for 90 minutes 
immediately prior to, during and for 90 minutes after the injection procedure, and again 
for 90 minutes at 2 and 4 weeks following the injection procedure.  
 
Below we describe each of these types of research evaluations. 
 
Questionnaires 
 
They will also complete questionnaires about mood and everyday functioning. They may 
refuse to answer any question that they don’t wish to answer. If they become 
uncomfortable at any time and wish to stop, the tests will be stopped. They may choose to 
fill out the questionnaires in either language These forms are: 
 
• Hot Flash Related Distress Scale (HFRDS) 
• Functional Assessment of Cancer Therapy-Breast (FACT-B) 
• Patient Global Impression of Change (PGIC) 
• Post-Injection Questionnaire  
 
Hot Flash Monitoring 
 
A research assistant will attach a hot flash monitor to the participant after they have 
completed the above mentioned. The hot flash monitor will be returned 24-hours later to 
the office via UPS or, at their convenience, a research assistant can meet them to 


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disconnect and collect the hot flash monitor at their doctor's office or back at the study 
site.  
 
The hot flash monitor we are using in this study is a small, lightweight, portable recorder 
that measures how many hot flashes you have each day. The monitor includes some wires 
and adhesive pads. The adhesive pads are attached to the skin on the chest just below the 
collarbones. Inside each adhesive pad is a small device that measures hot flashes. Wires 
send signals from the device to the monitor. Occasionally, the device may malfunction if 
the adhesive loosens or for other unknown reasons. Should this occur, they may be asked 
to wear the monitor for an additional 24 hours in order to collect missing objective hot 
flash data. The monitor measures 1 x 4 x 6 inches and weighs 8 ounces. The monitor is 
carried in a bag that is worn around the waist like a fanny pack. They will be given verbal 
instructions and handouts describing how to use the monitor.  
 
Actigraph Watch 
The research assistant will also instruct the participant on how to wear an Actigraph. An 
Actigraph is worn just like a watch and monitors sleep and wake habits. It should be 
removed for bathing, showering or swimming. They will be given verbal instructions and 
handouts describing how to use the actigraph watch. They will be given a prepaid return 
mailing box so that they can return the hot flash monitor and the Actigraph to us via UPS. 
 
Visit 3 (4-5 weeks after visit 1) 
 
Sympathetic nerve activity monitoring (SKNA) & Stellate Ganglion Injection Procedure 
 
The sympathetic nervous system activity monitor (SKNA) will be placed prior to the 
injection procedure. 2 electrodes will be placed over the anterior chest, similar to an 
ECG, and data will be collected for 90 minutes before the injection procedure while the 
participant is resting quietly in a sitting, reclining, or supine position.  The SKNA 
monitoring will continue throughout the injection procedure and for 90 minutes  
following the procedure.  
 
After the initial SKNA monitoring, but prior to the SGB, participants will be interviewed 
to assess health status and a brief physical exam will be performed by Dr. Walega. If they 
are determined to be a candidate for the procedure by Dr. Walega, he will randomize the 
participant into one of two groups: one group will receive the study procedure (stellate 
ganglion injection with local anesthetic or numbing medication) and the other will 
receive a sham procedure involving a saline injection in the superficial tissues of the right 
side of the neck in the region just below the skin layer.  
 
Assignment to groups will be done by randomization similar to flipping a coin, by 
opening a numbered opaque envelope with the group assignment noted inside. 
Participants will have a 50% chance of going into either of the two groups.  
 
The study will be single blinded. Participants will not know which group they are in and 
only Dr. Walega will know whether they have received the stellate ganglion injection 


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with numbing medication or the sham injection with saline. Since it is unknown how long 
the effects of the injection on hot flashes lasts, participants will have the option of 
receiving a second injection after the three month procedures if they notice an increase in 
the severity or frequency of their hot flashes. They will receive the same injection 
(bupivacaine or sham) that they got at the beginning of the study.   
 
Before the procedure, a medication line will be inserted into a vein in the arm. An oxygen 
monitor and blood pressure cuff will also be placed. They will be positioned on their back 
for this procedure. Their neck will be swabbed with disinfectant to clean the skin, and 
sterile equipment and technique will be used for the entire of the procedure. 
 
With the use of a low dose x-ray machine (fluoroscopy machine) to help guide the 
injection, a bone in the right side of the neck (C6) will be identified and local anesthesia 
or numbing medicine (1% lidocaine) will be injected to the skin overlying the bone.  
 
For subjects receiving the stellate ganglion injection, a small needle (22g or 25 g) will be 
placed through the numbed skin on the front of the right side of the neck to make contact 
with the tissues over the C6 (neck) bone. The correct position of this needle will be 
confirmed by injecting a small amount of dye that can be seen by Dr. Walega under x-
ray. Then 5 cc or about 1 teaspoon of 0.5% bupivacaine (numbing medicine) will be 
injected and the needle will be removed.  
  
In participants put in the sham injection group, the needle will be placed in the superficial 
tissues overlying the front right neck (C6 bone), just underneath the skin. 5 cc of saline 
fluid will be injected and the needle will be removed.   
 
The visual, tactile and auditory cues will be identical for both procedures.  The injection 
procedure will take a few minutes. Fluoroscopy times will be recorded. After the 
procedure is completed, they will stay in the office for about half an hour for observation. 
As during the procedure, blood pressure will be checked every 5 minutes and heart 
rate/pulse oximetry will be measured continuously. Temperature monitoring of the arm 
and hand, clinical evaluation for temporary drooping of the right eyelid, redness in the 
eye, congestion in the nose, and sweating on the right side of the face will be performed.  
 
Optional  (2 weeks after study procedure) 
They will be asked to return to the clinical site 2 weeks following the injection procedure. 
At this visit, only SKNA monitoring (90 minutes) will be performed. 
 
Optional (4 weeks after study procedure) 
They will be asked to return to the clinical site 2 weeks following the injection procedure. 
At this visit, only SKNA monitoring (90 minutes) will be performed. 
 
Visit 5 (3 months after study procedure) 
They will be asked to return to the clinical site 3 months following the injection 
procedure. At this visit, the same procedures listed in visit 2 will be performed.  
 


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The participant has the option to receive a second injection after the 3 month measures 
have been completed. If they choose to have one, they will be asked to return for a 
separate visit. No SKNA monitoring will be performed for the second injection. 
 
Visit 6 (6 months after study procedure) 
They will be asked to return to the clinical site 6 months following the injection 
procedure. At this visit, the same procedures listed in visit 2 (no SKNA monitoring) will 
be performed. 
 
Participants will continue to complete their hot flash diary for the duration of the study.  
Their part in this study will last for approximately seven months and will involve 6 visits. 
If they participate in the SKNA monitoring there will be 8 visits. Participants have the 
option to complete an additional diary for 6 months after the study. If they agree to do 
that, their participation may last 13 months. 
 
 
9.3 
Describe: Procedures performed to lessen the probability or magnitude of risks.  
Participants will be NPO in preparation for the injection procedure.  At the time of the 
injection procedure, an angiocatheter will be placed in the hand/arm for peripheral 
intravenous access as a safety precaution and a temperature monitor will be placed on the 
dorsum of both hands. Participants will be positioned supine in cervical extension. The 
anterior neck will be prepped with chlorhexidine and draped in the standard sterile 
manner. For active SGB, a right-sided SGB will be performed. Using fluoroscopic 
guidance, the C6 vertebra will be identified and the skin overlying the tubercle will be 
anesthetized using 2 mL of 1% lidocaine. Using digital pressure to laterally retract the 
carotid artery, a 25 or 22 g 1.5-inch needle will be placed to make contact with the 
anterolateral portion of the C6 vertebra and then retracted 1-2 mm and secured; contrast 
material (iopamidol 1-2 mL) will be injected with fluoroscopic guidance to confirm 
contrast dye spread in the prevertebral fascial plane and to rule out intravascular or 
intrathecal dye spread. 0.5% bupivacaine (5 mL) will be injected and the needle will be 
removed. Patients will have hemodynamic monitoring and oxygenation monitoring every 
5 minutes during the procedure and for the 30 minute recovery period as well. The 
recovery area is staffed by an RN. Emergency drugs and a crash cart with airway 
equipment and suction are in the Pain Medicine Center. 
 
Generally, any woman can safely have this injection unless she has an allergy to local 
anesthetic, contrast material, or has anatomic abnormalities of the anterior neck, all of 
which are rare. Drug interactions are a concern with other non-hormonal treatments for 
VMS, but not with SGB. The dose of local anesthetic needed to block the stellate 
ganglion does not cause toxic plasma levels of local anesthetic in the bloodstream and 
does not significantly interact with medications used for hypertension, asthma, 
depression, or seizures. 
 
With fluoroscopic guidance, contrast material (iopamidol 1-2 mL) will be injected to 
confirm contrast dye spread in the subcutaneous tissues, not in the prevertebral fascial 
plane of the stellate ganglion. Preservative-free saline (5 mL) will be injected and the 


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needle will then be removed. Participants will be transferred to a recovery area and 
monitored in a reclining position for at least 30 minutes to assess potential adverse effects 
of the injection. Presence of a Horner’s sign (miosis, ptosis, and anhydrosis) will be 
recorded and will validate successful SGB. Pre- and post-injection temperatures of the 
right hand will be measured and recorded. The research team will not have access to the 
injectionist's procedure notes in order to maintain the blind. Miosis, ptosis, and 
anhydrosis will not be considered adverse events as they are confirmatory for adequate 
SGB placement. 
 
• 
All drugs and devices used in the research and the purpose of their 
use, and their regulatory approval status.  
The study will use approved drugs (0.5% Bupivacaine, 1% Lidocaine and sterile saline) 
for unapproved uses (reduction in VMS). The package inserts have been uploaded into 
the "Supporting Documents" section of the IRB application. 
• 
The source records, including medical or educational records that 
will be used to collect data about subjects. (Attach all surveys, scripts, and data 
collection forms.) 
Copies of all surveys, diaries, subject instructions, and data collection forms have been 
uploaded under the" Supporting Documents" section of the IRB application. 
 
9.4 
What data will be collected, including long-term follow-up. 
Baseline data for subjective VMS frequency and severity will be recorded by 
participants in a written diary. Additional data for mood, sleep, and quality of life will be 
recorded, along with sociodemographic information related to the study participants in 
a case report form. The research chart and Case Report Form (CRF) will be maintained in 
the research office of Dr. Walega. 
 
9.5 
For HUD uses provide a description of the device, a summary of how you 
propose to use the device, including a description of any screening procedures, the HUD 
procedure, and any patient follow-up visits, tests or procedures. N/A 
 
10.0 Data and Specimen Banking-N/A 
10.1 
If data or specimens will be banked for future use, describe where the specimens 
will be stored, how long they will be stored, when they will be destroyed (if ever), how the 
specimens will be accessed, and who will have access to the specimens. 
10.2 
List the data to be stored or associated with each specimen. 
10.3 
Describe the procedures to release data or specimens, including: the process to 
request a release, approvals required for release, who can obtain data or specimens, and 
the data to be provided with specimens, including whether those data will be identifiable 
to others. 
11.0 Data and Specimen Management 
 
11.1 
Describe the data analysis plan, including any statistical procedures.  
 
Subjective VMS: As described in the determination of eligibility based on VMS entry 
criteria section for six months following the intervention, intensity of daytime VMS will 


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be calculated as follows: Intensity = Frequency*Severity = [(frequency of mild*1)+ 
(frequency of moderate*2) + (frequency of severe*3) + (frequency of very severe*4)] and 
used as a secondary endpoint. Frequency of night sweats will also be recorded daily via 
self-report the following morning. Baseline VMS frequency will be calculated as the 
mean of the daily count totals on diaries during the first two screening weeks. VMS 
frequency at Months 1 to 6 will be calculated as the mean of the daily count totals 
reported for the 30 days before each visit. 
 
Objective VMS: At baseline, and the 3- and 6-month post-intervention visits, 
participants will complete a second measure VMS objectively using the ambulatory 
sternal skin conductance monitor (Biolog Model 3991 x/2-HFI). Raw objective hot flash 
data will be analyzed by a combination of automated computer software and two trained 
data coders. According to standard procedures, once an objective hot flash will be coded, 
no other VMS will be coded for the next 15 minutes. Data will be independently double-
scored and double-entered into the database by coders blinded to treatment assignment. 
Participant sensitivity to objective HF will be calculated by dividing the total number of 
true positive hot flashes (i.e., objectively determined hot flashes that were subjectively 
detected) by the sum of the total number of objectively measured hot flashes (i.e., true 
positives and false negatives). Primary outcome measures will be total objective and 
subjective hot flashes in a 24-h period, during waking hours, and during sleeping hours.  
 
Sympathetic Nervous System Activity (SKNA): Monitoring will be done on the day of 
the study procedure for 90 minutes prior to, during and 90 minutes  after the intervention.  
Optional additional monitoring will be performed for 90 minutes at 2 weeks and 4 weeks 
post-intervention, Sympathetic nervous system activity is measured objectively using a 
non-invasive surface EMG monitor (Biomation ME6000 Biomonitor, Almonte, Ontario). 
2 electrodes are placed on the anterior chest wall similar to a standard electrocardiogram. 
Continuous EMG raw data will be filtered out and  be analyzed with proprietary software 
developed by Dr. Peng Chen at Indiana University. De-identified data will be sent to Dr. 
Chen’s lab at IU for analysis.  
 
Baseline characteristics: (e.g., sociodemographic variables, primary and secondary 
outcomes) will be compared between treatment groups using t-tests or chi-square tests for 
categorical variables. Multiple types of measurement outcomes (frequencies, counts, 
continuous and incidence outcomes) will be collected in this study. We will conduct 
intent-to-treat (ITT) analyses for all primary and secondary outcomes using a series of 
generalized mixed-effects regressions as described below. All statistical tests will be two-
sided with significance set at p≤.05. SAS statistical software version 9.2 (SAS Institute 
Inc., Cary, NC, USA) will be used for statistical analyses. In preliminary analysis, the 
distributional aspects of the variables under consideration will be examined through 
descriptive statistics. These statistics will include measures of location (mean, median, 
quartiles) and measures of dispersion (range, standard deviation, variance) for continuous 
variables and frequencies of the levels of categorical variables. These measures will also 
assist with a data cleaning/screening procedure to eliminate any possible copying, 
handling, recording or measurement errors. 
 


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In addition to the features described above, the dependence of outcome measures will 
need to be properly accounted for in the data analysis as measures will be made at 
multiple times for the same participant. Consequently, these observations tend to be 
correlated and require statistical techniques that can properly account for the correlation 
in order to draw valid inference. Our general approach for analyzing these multiple types 
of data in this trial will be the Generalized Linear Mixed-Effect Models (GLMM). These 
models can accommodate a wide range of outcomes including normal, binary, ordinal, 
and Poisson outcomes, while taking into account correlations from within-subject 
observations. To study the changes in outcomes over time and to evaluate group 
differences in these changes, we will construct GLMM models. The main independent 
variables in statistical model specifications typically include the group indicator, dummy 
variables for time, and the interactions between them, after controlling for observed and 
relevant covariates. By properly constructing GLMMs, a wide range of scientific 
hypotheses can be tested, including cross-sectional differences among groups, the effect 
of treatment over time and differences between groups over time. 
 
Data will be analyzed using the PROC MIXED, PROC GLIMMIX and PROC 
NLMIXED in SAS statistical software version 9.2.  
 
11.2 
Provide a power analysis, if necessary. 
Based on our prior studies, a sample size of 10 in each treatment group will provide at 
least 80% power to test the two-way interaction between Treatment and Time with a 
significance level set at 0.05. 
 
11.3 
Describe the steps that will be taken to secure the data to maintain 
confidentiality (e.g., training, authorization of access, password protection, encryption, 
physical controls, certificates of confidentiality, and separation of identifiers and data) 
during storage, use, and transmission 
 
Research files and case report forms will be stored in the research offices of Dr. Walega 
and will be kept in locked offices with access only to the research team. Wherever 
possible, subject data will be stored using only the study ID. Measures will be taken to 
protect all personal information and data, including keeping all data sheets under lock and 
key and entering data into a database that requires login identification and a password 
made available only to immediate study personnel. The entire study team has taken the 
CITI training and is familiar with confidentiality requirements and procedures.  
 
Downloaded data from the Biolog hot flash monitor and the actigraph watch will be 
processed, stored, and analyzed in password-protected network at the University of 
Illinois in Chicago of Dr. Pauline Maki. Downloaded deidentified data from the 
Biomation ME6000 monitor will be processed, stored, and analyzed in a password-
protected network at Indiana University of Dr. Peng Chen. 
 
Describe any procedures that will be used for quality control of collected data 
A computer-generated 1:1 block randomization scheme will be used to assign 
participants to receive either a SGB with bupivacaine or a sham injection with saline. 


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Randomization will be performed by Dr. Walega immediately before the injection 
procedure by opening an opaque envelope to reveal the participant number and group 
assignment printed on an index card. Randomization assignment will be kept under lock 
and key. Participants and all other study personnel, including those who will perform 
follow-up evaluations, will be blinded to group assignment. To ensure that Dr. Walega’s 
knowledge of randomization assignments does not influence study results, he will have 
no additional follow up or interaction with study participants, unless an adverse event 
occurs that requires his immediate attention. The study team will be briefed on the types 
of adverse events that require his attention. Dr. Walega will not be involved in the 
collection of any primary or secondary data outcome. 
 
11.5 Describe how data and specimens will be handled study-wide: see Section 11.0 
Data and Specimen Management 
 
11.6 What information will be included in that data or associated with the       
specimens? 
 See Section 11.0 Data and Specimen Management 
• 
Where and how data or specimens will be stored? 
See Section 11.0 Data and Specimen Management 
• 
How long the data or specimens will be stored? 
Data will be stored indefinitely. 
• 
Who (role on the study) will have access to the data or specimens? 
See Section 11.0 Data and Specimen Management 
• 
Who (role on the study) is responsible for receipt or transmission of 
the data or specimens?  
Dr. Walega at NU, Dr. Maki at UIC and Dr. Chen at IU are responsible for the receipt or 
transmission of data. They may designate a member of the research team to transmit data 
in accordance with NU/UIC IT security policies. 
• 
How data and specimens will be transported? 
See Section 11.0 Data and Specimen Management 
 
 
 
Provisions to Monitor the Data to Ensure the Safety of Subjects 
11.4 
Describe: 
• 
The plan to periodically evaluate the data collected regarding both 
harms and benefits to determine whether subjects remain safe.  The plan might include 
establishing a data monitoring committee and a plan for reporting data monitoring 
committee findings to the IRB and the sponsor. 
The study team will meet and review all adverse events after five subjects have been 
randomized and received the SGB procedure or sham. Per NU IRB protocol, all 
UPIRSO's or PRNCs will be reported a soon as the PI becomes aware of it. As the PI is 
the injectionist, the likelihood of missing a UPIRSO is highly unlikely. If no 
SAEs/UPIRSO's are observed, the team will meet again after 10 subjects have been 
randomized. No UPIRSOs or SAEs have occurred in previous studies.  


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• 
What data are reviewed, including safety data, untoward events, and 
efficacy data? 
Participants who undergo the SGB with bupivacaine will experience a temporary 
sympathetic block of the right upper extremity and right face for approximately 6-8 
hours. Efficacy of the SGB will be confirmed by the presence of Horner’s syndrome 
(miosis, abnormal contraction of the pupil; ptosis, drooping upper eyelid; and anhydrosis 
,absence of facial sweat) and a temperature increase of the affected extremity, the latter 
the result of regional venodilation. The temperature of the right upper extremity will be 
monitored prior to and 30 minutes following the injection to confirm, along with a 
Horner’s syndrome, successful SGB. These events are expected and confirm correct SGB 
placement. Events outside of those expected are what will be reviewed as stated above. 
The study team will be trained on the types of study related SAEs or AEs that should 
immediately be reported to the PI/IRB since they will not have access to the procedures 
records to maintain the blind.  
• 
How the safety information will be collected  
Safety data will be collected with case report forms, at study visits, and by telephone calls 
with participant. 
• 
The frequency of data collection, including when safety data 
collection starts. 
Safety data is collected as soon as the participant agrees to participate and signs the 
informed consent document.  
• 
Who will review the data? 
The PI will review the data with the study coordinator. 
• 
The frequency or periodicity of review of cumulative data. 
Efficacy data will be reviewed at the conclusion of the study. Safety data will be 
reviewed after 5 are randomized, then after 10 are randomized. Thereafter, safety data 
will be reviewed every 6 months provided that no UPIRSOs are observed in those that 
have received the study procedure.  
• 
The statistical tests for analyzing the safety data to determine 
whether harm is occurring. 
No statistical test will be used to determine whether harm is occurring. There is a 
preponderance of safety information on the SGB procedure that is familiar to the PI as 
this is his area of expertise. If the PI determines that unexpected SAEs and AEs are 
occurring in the SGB which is higher than seen in clinical practice, he will immediately 
cease enrollment and notify the IRB. 
• 
Any conditions that trigger an immediate suspension of the research. 
A participant study related death will trigger an immediate suspension of the research. 
12.0 Withdrawal of Subjects* 
12.1 
Describe anticipated circumstances under which subjects will be withdrawn 
from the research without their consent, including stopping participation for safety 
reasons. 
The PI can remove subjects from the research study without their approval. Possible 
reasons for removal include the following: if it appears to be medically harmful to the 
subject, or if they fail to follow directions for participating in the study, such as taking 
excluded medication (aspirin, anti-coagulants) prior to the SGB procedure, if it is later 


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discovered that they did not meet the study eligibility requirements, at the discretion of 
the study doctor or, if the study is canceled. 
12.2 
Describe any procedures for orderly termination. 
A subject who withdraws will be scheduled to return to the research office. At this time, 
written diaries will be collected and AEs will be assessed, if any. Prior to scheduling the 
appointment, the subject will be asked if she would like to see the PI. If yes, this will be 
done on the same visit. If a subject does not wish to return, she will be asked to mail or 
fax any written diaries. Final payment will be mailed to the subject if compensation has 
not already been paid out. 
12.3 
Describe procedures that will be followed when subjects withdraw from the 
research, including partial withdrawal from procedures with continued data collection. 
Subjects only have the option of not participating in the 2 and 4 week SKNA monitoring.. 
All other procedures are required as part of the study. The subject has the option to 
withdraw if she does not want to participate in the hot flash monitoring, actigraph 
monitoring and most importantly, maintaining a written diary for the duration of the 
study. 
13.0 Risks to Subjects* 
13.1 
List the reasonably foreseeable risks, discomforts, hazards, or inconveniences to 
the subjects related the subjects’ participation in the research. Include as may be useful 
for the IRB’s consideration, describe the probability, magnitude, duration, and 
reversibility of the risks. Consider physical, psychological, social, legal, and economic 
risks. 
There are risks associated with participation in this study. Below is a description of the 
risks: 
 
Stellate Ganglion Block with local anesthetic  
 
Stellate ganglion injection carries the potential very rare risk of infection at the injection 
site, bleeding or blood clot formation at the injection site, seizures (sudden, uncontrolled 
muscle spasms and loss of consciousness) and nerve injury which may present as 
temporary parasthesia (numbness) and/or weakness.  All of these rare risks are minimized 
with the use of fluoroscopic guidance (visualization with a type of x-ray) and 
hemodynamic/oxygenation monitoring. Other complications related to the stellate 
ganglion injection that can occur are puncture of the lung on the right during placement 
of the needle on the right neck, or an allergic reaction to the medications being injected 
into the subject. Temporary voice hoarseness, temporary mild shortness of breath, 
temporary difficulty swallowing, and temporary changes in blood pressure may occur 
after the stellate ganglion injection from the numbing medicine.  Possible reactions from 
the numbing medicine used in this study last 6-8 hours.   Minor soreness at the injection 
site could last 1-2 days. 
 
Tissue injection of saline (sham) below the surface of the skin 
 
Needle placement carries the potential very rare risk of infection at the injection site, 
bleeding or blood clot formation at the injection site, temporary swelling of the right side 


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of the neck from the injected liquid and an allergic reaction to the medications being 
injected into you.  Minor soreness at the injection site could last 1-2 days.   
 
Risk of Radiation from the x-ray 
 
The contact with radiation in this study is thought to be small. However, the effects of 
radiation add up over a lifetime. It is possible that having several of these X-rays may add 
to the subject's risk of injury or disease. When deciding to enter this study, subjects will 
be asked to consider past and future contact with radiation. Examples of contact with 
radiation include x-rays or CT scans taken for any reason or radiation therapy for cancer 
treatment.  
 
Risks from the hot flash monitor  
 
The hot flash monitor does not involve significant risk. Wearing the monitor can be a 
minor inconvenience. The monitor poses no risk of electric shock. Potential side effects 
of the monitor include (1) allergy to the paper or adhesive on the disposable electrodes 
(minor, 1%), (2) itching at the site of electrode attachment (minor, 4%) and (3) 
discoloration of the skin from the electrode gel.  
 
Risks with the Actigraph watch  
The Actigraph watch does not involve significant risk. Wearing the watch can be a minor 
inconvenience, and the band may cause slight irritation. 
 
Risks from the SKNA monitor  
 
The SKNA monitor does not involve significant risk. Wearing the monitor can be a 
minor inconvenience. The monitor poses no risk of electric shock. Potential side effects 
of the monitor include (1) allergy to the adhesive on the disposable electrodes (minor, 
1%) and (2) itching at the site of electrode attachment (minor, 1%). 
 
Questionnaires 
 
Being in this study may make the subject feel emotionally uncomfortable. They might 
feel anxious, or experience emotional reactions to some of the questions that will be 
asked. 
 
Confidentiality Risks 
 
There is a risk of loss of confidentiality. Certain measures are taken to protect all personal 
information and data, including keeping all data sheets under lock and key and entering 
data into a non-network database that requires a login id and password made available 
only to immediate study personnel. 
 
13.2 
If applicable, indicate which procedures may have risks to the subjects that are 
currently unforeseeable. 


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Currently, there are no unforeseeable risks to the study procedures. 
 
14.0 Potential Benefits to Subjects 
14.1 
Describe the potential benefits that individual subjects may experience from 
taking part in the research. Include as may be useful for the IRB’s consideration, the 
probability, magnitude, and duration of the potential benefits. 
Possible benefits include a reduction in the severity or frequency of hot flashes, an 
improvement in overall feeling of well-being and ability to perform the functions of daily 
living impacted by hot flashes. We do not know how long these benefits will last. 
 
14.2 
Indicate if there is no direct benefit. Do not include benefits to society or others. 
Subjects who receive the sham procedure will have no direct benefit from participation. 
 
15.0 Vulnerable Populations -N/A 
 
16.0 Community-Based Participatory Research-N/A 
 
Sharing of Results with Subjects 
16.1 
Describe whether results (study results or individual subject results, such as 
results of investigational diagnostic tests, genetic tests, or incidental findings) will be 
shared with subjects or others (e.g., the subject’s primary care physicians) and if so, 
describe how it will be shared. 
Study results will not be shared with subjects as they are considered experimental and are 
not required or related to their on-going medical care. 
 
17.0 Setting 
17.1 
Describe the sites or locations where your research team will conduct the 
research. 
Northwestern Medicine, formerly the Northwestern Medical Faculty Foundation, 
maintains a newly constructed 11,000 square foot dedicated Pain Medicine Clinic located 
on the 14th floor of the Lavin Pavilion at the Northwestern University Chicago campus. 
The stellate ganglion blockade or sham injection will take place in one of the two 
fluoroscopy suites and post procedure monitoring will be done in the 6 bay recovery 
rooms at this facility. 
Consenting, questionnaire completion and cognition testing will take place in the research 
office of Dr. Walega at 259 East Erie, Suite 1400 in the Lavin Pavilion. 
• 
Identify where your research team will identify and recruit potential 
subjects. 
IRB approved flyers and physician provider letters will be utilized for the study. See 
"Supporting Documents" section. We expect that potential subjects will contact the 
research office as a result of the recruitment aids or will be referred to us by health 
providers. 
18.0 Resources Available 
18.1 
Describe the qualifications (e.g., training, experience, and oversight) of you and 
your staff as required to perform their role. When applicable describe their knowledge 


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of the local study sites, culture, and society. Provide enough information to convince 
the IRB that you have qualified staff for the proposed research. You do not need to list 
individual names of your staff in this protocol. 
Dr. Walega is the Chief of the Division of Pain Medicine.  This clinical trial is funded by 
the Friends of Prentice Grant Initiative which was awarded to Dr. Walega based on the 
merit of the project.  
 
Dr. Cesar Santa-Maria is an Assistant Professor in the Department of Medicine in the 
Hematology/Oncology Division. His clinical practice is devoted solely to breast cancer 
treatment and about 25% of his patients are Hispanic women.  He will serve as Co-
investigator for this study and his main role will be in recruitment as he interfaces with 
Hispanic women with breast cancer on a daily basis.  
 
Dr. Shulman is a Professor of Obstetrics and Gynecology at Northwestern University, the 
Director of the Ovarian Cancer Early Detection and Prevention Program and Co-Director 
of Cancer Genetics Program at Northwestern. He will serve as Co-investigator for this 
study. His role as the Co-Director of the cancer genetics program allows him to interface 
with the team in facilitating recruitment for women with breast cancer with moderate to 
severe hot flashes.  
 
Pauline M. Maki, PhD, is Professor of Psychiatry and Psychology at UIC and Director of 
the Women’s Mental Health Research Program. She will oversee the collection, scoring, 
management, and interpretation of secondary outcome measures: namely objective hot 
flash monitoring, and actigraphy.  
 
Dr. Peng Chen, MD, PhD is a Professor of Cardiology at Indiana University where he is 
also the Chairman of the Department of Cardiology and maintains his own lab.  He will 
assist in the handling and analysis of SKNA data for Dr. Walega. 
 
Ms. Banuvar is a Clinical Research Associate and has a long history of collaboration with 
Dr. Walega, Dr. Maki and Dr. Shulman and has worked on three projects related to 
vasomotor symptoms with this team. She will be responsible for data integrity and 
protocol maintenance and recruitment. She will monitor the subjective hot flash diary 
data collection of subjects and assist with placement of the Biolog hot flash monitor and 
Actiwatch.She will also assist the PI in monitoring and reporting adverse events as well 
as correspondence with NU IRB.  
 
18.2 
Describe other resources available to conduct the research: For example, as 
appropriate: 
At UIC under the supervision of Dr. Maki, all computers have access to a secure server 
which is accessed through a unique IT department provided log-in. All electronic data are 
stored on the secure server. Only delegated logins have the ability to view or edit the 
information stored in on this server. Currently two of the 10 computers are equipped with 
a Biolog Transfer box, Biolog DPS software (for downloading and convert Biolog data) 
and Biolog 3.7, the most recent version of the software used to score and edit the Biolog 
data. Eight computers are currently equipped with the Actiware software (version 5.7) 


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which is used to configure, download and score Actiwatch data. The downloading 
platform can be moved between computers as needed. 
 
At IU under the supervision of Dr. Chen, all computers have access to a secure server 
which is accessed through a unique IT department provided log-in. All electronic data are 
stored on the secure server. Only delegated logins have the ability to view or edit the 
information stored in on this server. Currently several computers in Dr. Chen’s lab are 
equipped with the proprietary software that can interpret SKNA data and convert it to a 
proxy of sympathetic nervous system activity. The downloading platform can be moved 
between computers as needed. 
• 
Justify the feasibility of recruiting the required number of suitable 
subjects within the agreed recruitment period. For example, how many potential 
subjects do you have access to? What percentage of those potential subjects do you 
need to recruit? 
Based on our experience with previous studies, we estimate we would need to screen 50 
women to randomize 20 women. This is a small sample size. We do not anticipate 
problems in obtaining a complete sample size over the next year. 
• 
Describe the time that you will devote to conducting and completing 
the research. (Note: This description is intended to provide the IRB with information 
relative to conduct of the study as relevant for the protection of research subjects, not 
for effort reporting.) 
We anticipate that the study team will contribute 2 days per week to the project. 
• 
Describe your facilities. (Note: This description is intended to 
provide the IRB with information relative to conduct of the study as relevant for the 
protection of research subjects, not for Facilities and Administration considerations.) 
Already addressed in Section 17.0 and 18.0. 
• 
Describe the availability of medical or psychological resources that 
subjects might need as a result of an anticipated consequences of the human research. 
• 
Describe your process to ensure that all persons assisting with the 
research are adequately informed about the protocol, the research procedures, and 
their duties and functions. 
Prior to the inception of the study and after IRB approval has been obtained, the research 
team will meet to review the protocol. Safety endpoints will be reviewed and study 
logistics will be coordinated and agreed upon.  
    
19.0 Prior Approvals 
19.1 
Describe any approvals that will be obtained prior to commencing the research. 
We will obtain radiation safety by means of the Radiation Dosimetry Form. 
 
20.0 Recruitment Methods 
20.1 
Describe when, where, and how potential subjects will be recruited. 
IRB approved flyers and physician provider letters will be utilized for the study. See 
"Supporting Documents" section. We expect that potential subjects will contact the 
research office as a result of the recruitment aids or will be referred to us by health 
providers. Subjects will be asked to come to the research office for consenting if they are 
interested in the study.  


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20.2 
Describe the source of subjects. 
We expect that the majority of subjects will come from the practices of Northwestern 
Medicine providers. 
 
20.3 
Describe the methods that will be used to identify potential subjects. 
IRB approved flyers, physician provider letters and internet notices will be utilized for 
the study. See "Supporting Documents" section. 
 
20.4 
Describe materials that will be used to recruit subjects. (Attach copies of these 
documents with the eIRB+ application. For advertisements, attach the final copy of 
printed advertisements. When advertisements are taped for broadcast, attach the final 
audio/video file. You may submit the wording of the advertisement prior to taping to 
preclude re-taping because of inappropriate wording, provided the IRB reviews the 
final audio/video file.) 
See "Supporting Documents" section. 
 
20.5 
Describe the amount, timing, and method of any payments to subjects. (E.g., 
Gift card, Clinker, check.) 
The study will pay for parking in the hospital parking lot located on St. Clair St., between 
Superior and Huron Streets. Their parking ticket will be validated by the research staff 
and paid for up to six hours. 
 
Subjects, who agree to take part in this research study, will be paid $200.00 by check at 
study completion for time and effort. They may choose to have the final check mailed to 
them, or they may come to the clinic to retrieve their check if that is more convenient. 
They will receive an additional $75.00 (up to $150.00) for the 2 optional SKNA 
monitoring visits and $100 if they choose to complete the hot flash diary for an additional 
6 months totaling up to $450 for participation.. 
 
21.0 Local Number of Subjects 
 
21.1 
Indicate the total number of subjects to be accrued locally 20 
21.2 
If applicable, include a break-down of subjects by study location or procedure 
group 10 women will be in the SGB procedure group and 10 women will be in the sham 
group. All women will be recruited and followed at Northwestern. 
 
21.3 
If applicable, distinguish between the number of subjects who are expected to 
be enrolled and screened, and the number of subjects needed to complete the research 
procedures (i.e., numbers of subjects excluding screen failures.) 
20 enrolled subjects are required to complete the study. We estimate that we would need 
to screen approximately 50 women to randomize 20 women. 
 
22.0 Confidentiality-Repetitive  


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These issues have already been addressed in the Data and Specimen Management Section 
11.3 to 11.4. 
 
22.1 
If this is a multicenter study, describe the local procedures for maintenance of 
confidentiality. 
• 
Where and how data or specimens will be stored locally? 
• 
How long the data or specimens will be stored locally? 
• 
Who will have access to the data or specimens locally? 
• 
Who is responsible for receipt or transmission of the data or 
specimens locally? 
• 
How data and specimens will be transported locally? 
• 
 
23.0 Provisions to Protect the Privacy Interests of Subjects 
 
23.1 
Describe the steps that will be taken to protect subjects’ privacy interests. 
“Privacy interest” refers to a person’s desire to place limits on with whom they interact 
or to whom they provide personal information. 
Potential subjects do not have to authorize the use or disclosure of their health 
information; however, they will not be allowed to take part in this research study. They 
may also revoke authorization for use or disclosure of their health information in writing. 
Direct personal identifiers will not be used in the database. In addition, unless disclosure 
of the direct identifier is necessary for review by regulatory authorities or is required by 
law, access to direct identifiers will be strictly limited to research team delegates of the 
PI.  
23.2 
Describe what steps you will take to make the subjects feel at ease with the 
research situation in terms of the questions being asked and the procedures being 
performed. “At ease” does not refer to physical discomfort, but the sense of 
intrusiveness a subject might experience in response to questions, examinations, and 
procedures. 
Subjects will be reassured that if there are questions in the surveys that they do not want 
to answer or if some of the questions make them uncomfortable, they do not have to 
answer them. In addition, if they have questions or concerns about the study procedures 
the research team, including the PI, is available to them for the duration of the study. 
They will be told that they do not have to wait for study related clinic visits to be seen or 
assessed for any concern. 
23.3 
Indicate how the research team is permitted to access any sources of 
information about the subjects. (E.g., What permission does the research staff have to 
access medical records or other sensitive information?) 
HIPAA Authorization will be obtained from all research subjects through the consent 
document. Subjects will give us the permission to use personal health information that 
includes health information in the medical records and information that can identify 
them. Personal health information may include the subject's name, address, phone 
number or social security number. Health information we may collect and use for this 
research includes:  
• All information in a medical record  


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• Results of physical examinations 
• Medical history 
• Lab tests, or certain health information indicating or relating to a particular 
condition as well diaries and questionnaires 
• Records about study medication or drugs 
• Substance abuse information: current substance abuse is an exclusion to 
participation in the study 
• Mental Health information: history of depression, psychosis and concomitant 
medication 
• Dr. Pauline Maki from The University of Illinois at Chicago, Department of 
Psychiatry and her research assistants working directly under her supervision, 
may also receive, or use health information. The reason for sharing this data with 
these individuals is that UIC personnel may be involved in the collection of hot 
flash data, actigraph data. Questionnaire data and cognitive test results. 
 
 
 
24.0 Compensation for Research-Related Injury 
 
24.1 
If the research involves more than Minimal Risk to subjects, describe the 
available compensation in the event of research-related injury. 
Subjects who need medical care because of taking part in this research study may seek 
medical treatment through the investigator or a treatment center of their choice.  The care 
will be billed to the subject, or their insurance. The study has no program to pay for 
medical care for research-related injury. 
 
24.2 
Provide a copy of contract language, if any, relevant to compensation for 
research-related injury. N/A 
 
25.0 Economic Burden to Subjects 
 
25.1 
Describe any costs that subjects may be responsible for because of participation 
in the research. 
There are no costs to the subject for participation in the research. 
 
26.0 Consent Process 
26.1 
Indicate whether you will you be obtaining consent, and if so describe: 
Written informed consent will be obtained from every subject. 
• 
Where will the consent process take place 
Consent will take place in the research office of Dr. Walega and his team. 
• 
Any waiting period available between informing the prospective 
subject and obtaining the consent. 
The waiting period available is solely at the discretion of the participant. If the subject 
learns of the study via a flyer or provider and telephones the research office, the subject 
will be asked to present to the research office in order for written informed consent to be 


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obtained in person. Alternatively, if the subject learns of the study in a clinical setting, if 
the research team is available and if a private space is available, the team member can go 
to the subject to conduct the informed consent process and obtain written consent. 
• 
Any process to ensure ongoing consent. 
The PI will again ask the subject prior to administration of the study procedure whether 
they have had any additional questions or concerns and whether they still wish to 
continue their participation. 
• 
Whether you will be following “SOP: Informed Consent Process for 
Research (HRP-090).” If not, describe: 
“SOP: Informed Consent Process for Research (HRP-090)” will be followed for this 
study. 
o 
The role of the individuals listed in the application as being 
involved in the consent process. 
o 
The time that will be devoted to the consent discussion. 
The discussion will take as long as is needed to insure that the subject has fully read the 
document and expresses understanding. For this study, we plan to allow 1 hour for the 
consent discussion but it may be extended if needed. 
o 
Steps that will be taken to minimize the possibility of coercion 
or undue influence. 
o 
Although Dr. Walega will be overseeing the consent process, he 
will not be directly obtaining consent. It is unlikely that these study patients will be ones 
he may be treating in his Pain Clinic so there would likely be no concern for undue 
influence as the treating physician. 
o 
Steps that will be taken to ensure the subjects’ 
understanding. 
Individuals involved in the consent process will dialogue with the subject to insure they 
understand what is required. They will be bilingual. Participants may be asked to 
summarize their understanding of the goals and procedures of the study. Care will be 
given to ensure they do not feel like they are being "tested". 
 
Non-English Speaking Subject-NA 
Waiver or Alteration of Consent Process (consent will not be obtained, required 
information will not be disclosed, or the research involves deception)-N/A 
Subjects who are not yet adults (infants, children, teenagers) -N/A. 
Cognitively Impaired Adults-N/A 
Adults Unable to Consent-N/A 
 
27.0 Process to Document Consent in Writing 
 
27.1 
Describe whether you will be following “SOP: Written Documentation of 
Consent (HRP-091).” If not, describe whether and how consent of the subject will be 
documented in writing. 
“SOP: Written Documentation of Consent (HRP-091)” will be followed for this study. 
 
27.2 
If you will document consent in writing, attach a consent document in your 
eIRB+ application.  


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Consent document is included in Supporting Documents Section. 
 
28.0 Drugs or Devices 
 
28.1 
If the research involves drugs or devices, describe your plans to store, handle, 
and administer those drugs or devices so that they will be used only on subjects and be 
used only by authorized investigators. 
Dr. Walega will be solely responsible for administering the drugs to be used in this study. 
They will be stored in the Anesthesiology Pain Medicine Clinic as these drugs are 
typically used as part of the standard of care for SGB and other clinic procedures. 
 
28.2 
If the drug is investigational (has an IND) or the device has an IDE or a claim 
of an abbreviated IDE (non-significant risk device), include the following information: 
N/A 
 
 
Literature 
1. Carpenter JS, Johnson D, Wagner L, Andrykowski M. Hot flashes and related 
outcomes in breast cancer survivors and matched comparison women. Oncology Nursing 
Forum. 2002; 29(3): E16-25. 
2.Gupta P, Sturdee DW, Palin SL, Majumder K, Fear R, Marshall T, et al. Menopausal 
symptoms in women treated for breast cancer: the prevalence and severity of symptoms 
and their perceived effects on quality of life. Climacteric. 2006; 9(1): 49-58. 
3.Land SR, Wickerham DL, Costantino JP, Ritter MW, Vogel VG, Lee M, et al. Patient-
reported symptoms and quality of life during treatment with tamoxifen or raloxifene for 
breast cancer prevention: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 
trial. JAMA. 2006; 295(23): 2742-51. 
4.Hunter MS, Grunfeld EA, Mittal S, Sikka P, Ramirez AJ, Fentiman I, et al. Menopausal 
symptoms in women with breast cancer: prevalence and treatment preferences. 
Psychooncology. 2004; 13;769-78. 
5. Baber R, Hickey M, Kwik M. Therapy for menopausal symptoms during and after 
treatment for breast cancer: safety considerations. Drug Saf. 2005; 28(12): 1085-100. 
6. Hickey M, Saunders CM, Stuckey BG. Management of menopausal symptoms in 
patients with breast cancer: an evidence-based approach. Lancet Oncol. 2005; 6(9): 687-
95.     
7. Cella D, Fallowfield LJ. Recognition and management of treatment-related side effects 
for breast cancer patients receiving adjuvant endocrine therapy. Breast Cancer Res Treat. 
2008; 107(2): 167-80. 
8.Pachman DR, Barton D, Carns PE, Novotny PJ, Wolf S, Linquist B, et al. Pilot 
evaluation of a stellate ganglion block for the treatment of hot flashes. Supportive Care in 
Cancer. 2011; 19(7): 941-7. 
9.Lipov EG, Joshi JR, Sanders S, Wilcox K, Lipov S, Xie H, et al. Effects of stellate-
ganglion block on hot flushes and night awakenings in survivors of breast cancer: a pilot 
study. Lancet Oncol. 2008; 9: 523-32. 
10.Haest K, Kumar A, Van Calster B, Leunen K, Smeets A, Amant F, et al. Stellate 
ganglion block for the management of hot flashes and sleep disturbances in breast cancer 


Title:   Hispanic SGB Breast CA Study  
 
Version January 5, 2017,  
Page 29 of 29 
Revised Template: November 10, 2014 
survivors: an uncontrolled experimental study with 24 weeks of follow-up. Annals of 
Oncology. 2012; 23(6): 1449-54. 
11. Walega DR, Maki PM, Rubin LH, Banuvar S, Shulman LP.  Effects of Stellate 
Ganglion Blockade on Vasomotor Symptoms: Findings from a Randomized Clinical 
Trial of Postmenopausal Women. Menopause Aug 2014 PMID 24496086  
12. Maki PM, Rubin LH, Savarese A, Walega DR, Banuvar S, Shulman LP. Reductions 
in Vasomotor Symptom Following Stellate Ganglion Blockade are Related To 
Improvements in Memory.  Maturitas 2014 (accepted for publication) 
13. Wulf H, Maier C. Complications and side effects of stellate ganglion blockade. 
Results of a questionnaire survey. Anaesthesist. 1992; 41(3): 146-51. 
14. Otthman AH, Zaky AH. Management of Hot Flushes in Breast Cancer Survivors: 
Comparison between Stellate ganglion Block and Pregabalin. 
15. Guttuso T. Stellate ganglion block for treating hot flashes: a viable option or sham 
procedure? Maturitas 2013; 76:221-224. 
16. Walega DR, Maki PM. Letter to the Editor:  Effects of Stellate Ganglion Blockade on 
Vasomotor Symptoms: Findings from a Randomized Clinical Trial of Postmenopausal 
Women. Menopause 2014. PMID 24937028