A Pilot Study to Assess Effects of Self-Administered Nitrous Oxide (SANO) on Urodynamic Study (UDS) Parameters
Phase: PHASE4
Conditions: Lower Urinary Tract Symptoms
Sponsor: Beth Israel Deaconess Medical Center

(CCI) Committee on Clinical Investigations 
Page 1 of 15 
 
Study Description – Part B 
CCI Form:  9-2015 
 
 
PI Revision Date:  
December 16, 2022 
 
Study Protocol Cover Page 
 
 
Study Protocol 
 
ID: 2022P-000826 
 
A Pilot Study to Assess Effects of Self-Administered Nitrous Oxide (SANO) on Urodynamic 
Study (UDS) Parameters 
 
 
 
Please note: the Statistical Design included in this Protocol has been updated, and is included 
separately. 
 
 

(CCI) Committee on Clinical Investigations 
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Study Description – Part B 
CCI Form:  9-2015 
 
 
PI Revision Date:  
December 16, 2022 
 
 
PART B 
STUDY DESCRIPTION 
 
TITLE OF PROTOCOL 
A Pilot Study to Assess the Effects of Self-Administered 
Nitrous Oxide (SANO) on Urodynamic Study (UDS) 
Parameters 
Principal Investigator 
Heidi Rayala, MD PhD  
 
B1. 
PURPOSE OF PROTOCOL 
A Urodynamic Study (UDS) is a diagnostic procedure commonly performed by Urologists in the 
ambulatory setting to diagnose urinary dysfunction.  A UDS is generally considered to have low 
morbidity, but patients may find it uncomfortable and anxiety provoking, partly because the study 
involves placing both a urethral and abdominal pressure catheter.  The abdominal pressure 
catheters are placed in the rectum (for men and children) and the vagina (for women).  
Additionally, there are EMG electrodes placed at the anal sphincter, and in some patients 
(primarily children) these are needle electrodes.  In adults, studies show that after a UDS, 15-26% 
of patients would not elect to undergo the UDS procedure again (Yokoyama, 2005).  In children, 
distress rates can be as high as 61-71% during UDS (Herd, 2006). There have been multiple studies 
that have looked at ways to decrease the anxiety and discomfort experienced by patients during a 
UDS, including use of music, videos, and dimming of lights, all with varying effect.  There are also 
studies that have looked at the use of medications such as ketamine or midazolam to reduce the 
pain and anxiety during UDS; however, in principle, UDS should not be performed when the 
patient is sedated as there is constant verbal feedback that is required throughout the testing 
process.   
 
Nitrous oxide is an inhaled analgesic that is used in pediatric and adult populations for ambulatory 
procedures, and is largely viewed as effective and safe.  Nitrous oxide also produces a dissociative 
euphoria and amnesia that could potentially improve patients' anxiety and experience of care 
during painful or anxiety provoking procedures.  We have used patient self-administered nitrous 
oxide (SANO) in our ambulatory clinic at BIDMC for men undergoing prostate biopsies with good 
effect and no significant complications.  SANO may offer an appealing option for patients who are 
reluctant to undergo an initial UDS or for those who have not tolerated the study in the past.  
What we do not know is whether a UDS performed under the influence of SANO will give study 
results that are accurate and reproduce the bladder function of the patient during their daily 
routine.  In a pediatric population, both ketamine and midazolam have been shown to provide 
satisfactory sedation without impacting UDS values (Thevaraja, 2012); however, sedation with 
propofol does negatively impact outcome values (Merguerian, 2006).  No studies to date assess 
whether the administration of SANO will negatively impact UDS results.  It is possible that SANO 
will perform better than ketamine or midazolam, as it is anticipated SANO will reduce anxiety and 
perception of pain without causing a sedative effect.  
 
We propose a pilot study with 25 patients (14 randomized) to compare the impact of SANO vs 
Oxygen on UDS parameters of patients undergoing routine UDS. Study procedures will take place 
in the Clinical Research Center (ST 802, Gryzmish 8).  Our primary aim will be to assess whether 
SANO has any adverse effects on routinely measured UDS variables. We will assess whether 

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Study Description – Part B 
CCI Form:  9-2015 
 
 
PI Revision Date:  
December 16, 2022 
 
periprocedural SANO negatively impacts operator productivity or increases the difficulty in 
performing the UDS. A secondary aim will be to assess patient perceived pain and anxiety related 
to catheter placement and experience of SANO during the UDS. 
 
Specific Aims:  
Aim 1: To demonstrate that Self-Administered Nitrous Oxide (SANO) at the time of Urodynamic 
Study (UDS) does not significantly impact outcome variables during the study. 
Hypothesis 1.1: Administration of periprocedural SANO will not impact core UDS outcomes 
of “Bladder Capacity”, “Maximum Flow Rate”, and “Maximum Detrusor Pressure”  
Hypothesis 1.2: Administration of periprocedural SANO will not significantly lengthen the 
time of the procedure  
Hypothesis 1.3: Administration of periprocedural SANO will allow the operating APP to 
perform the procedure with the same ease as on those patients who do not have SANO. 
Aim 2: To assess effectiveness of SANO in decreasing patient perceived anxiety and pain related to 
UDS.  
Hypothesis 2.1: Administration of periprocedural SANO will improve patients’ experience  
during the UDS as measured by VAS (visual analogue scale) score. 
Hypothesis 2.2: Administration of periprocedural SANO will result in minimal side effects for 
the patients and will allow the patient to drive home independently. 
 
 
 
B2. 
SIGNIFICANCE AND BACKGROUND FOR THE STUDY 
Burden of Urodynamic Study 
Urodynamic testing is an ambulatory procedure that is considered the gold standard for evaluating 
lower urinary tract symptoms (LUTS) in both female and male patients. Though not required for all 
patients with LUTS, a UDS can be particularly helpful in evaluating those patients who do not 
respond to first line treatment algorithms for LUTS.  There are certain patient populations, such as 
children and adults with spina bifida, who require routine UDS evaluations to assess for worrisome 
changes that may result in damage to their urinary system.  Many of these patients can develop an 
increasing reluctance to undergo UDS due to poor memories of prior experience.  Studies have 
shown that up to 26% of patients are unwilling to undergo a future UDS (Yokoyama, 2005). In part, 
this dissatisfaction is due to the innate discomfort of the procedure; however, embarrassment and 
shame during UDS has also been found, especially in women (Yeung, 2014).  Children may 
particularly bear a significant burden during UDS, with studies showing “serious” or “severe” 
distress in 61% of children undergoing UDS (Herd, 2006). 
 

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Study Description – Part B 
CCI Form:  9-2015 
 
 
PI Revision Date:  
December 16, 2022 
 
Nitrous Oxide as an adjunct for Procedural Pain 
Inhaled nitrous oxide is commonly used for patient analgesia and anxiolysis outside of the US, and 
is gaining traction in the US.  For example, use of nitrous oxide during labor occurs in 43% of 
Canadian deliveries and 62% of deliveries in the UK (Rooks, 2007).  This has led to recent adoption 
and promulgation of nitrous oxide by AWHONN (Association of Women’s Health Obstetric and 
Neonatal Nurses) as a “vital component in the provision of quality of maternity care” (Practice 
Brief, 2018).  Nitrous oxide has also been adopted in US pediatric clinical settings, including Boston 
Childrens Hospital’s Emergency Department. 
 
Administration: 
During self-administered nitrous oxide (SANO) a patient holds a gas mask to their own face, and 
works with the medical team to titrate the nitrous level to optimum concentration level.  SANO is 
administered as a single agent of nitrous oxide, at concentrations <50%.  At these levels, nitrous 
oxide is classified by the American Society of Anesthesiologists (ASA) as “mild sedation”, which 
does not require the presence of anesthesia personnel, NPO status, nor escort home. Current 
literature states that “patients could safely operate a motor vehicle after N2O/O2 sedation” (Clark 
et al., 2020). An additional study performed by Hawkins, et al. similarly concludes that there does 
not appear to be any residual cortical effects from mild sedation with nitrous oxide. The recovery 
period was established to be three to five minutes following termination of nitrous oxide, and the 
expectation that participants would “return to normal at the first post-treatment determination 
(five minutes post-operative)” was confirmed. In each study, participants were given a 50-50 
mixture of N2O/O2, and concentrations of NO2 between 35-50% (Clark et al., 2020). This closely 
mirrors our protocol’s administration of nitrous oxide, as we are administering concentrations of 
25-45%.   
 
The Nitrouseal® system has an adjustable-concentration digital flowmeter and includes an FDA-
cleared exhaled waste gas scavenger, the Miniscav®. The Nitrouseal® system includes a proprietary 
disposable single-use full-face mask and breathing circuit that collects and contains the exhaled 
nitrous gas before it is scavenged into the Miniscav®. 
 
The Nitrouseal® has been used in urology since 2017 in procedures such vasectomies, 
cystoscopies, UroLift® implants, bladder biopsies, prostate biopsies and Botox injections, with 
reported improvement in patient anxiety, relaxation and comfort. However, there have been no 
controlled studies in the US that have studied the effects of nitrous oxide for UDS. 
 
 
 
 

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Study Description – Part B 
CCI Form:  9-2015 
 
 
PI Revision Date:  
December 16, 2022 
 
B3. 
DESCRIPTION OF RESEARCH PROTOCOL 
A. 
Study Design – Overview, Methods, Procedures 
 
METHODS AND PROCEDURES: 
Screening  
After the Urologist has discussed and planned for office urodynamic study, a baseline examination by 
the clinical team for eligibility verification will be performed through a medical record review by a 
trained member of the research staff.   
 
Recruitment and Obtainment of Informed Consent 
A member of the research team will reach out by phone call and/or PatientSite email at least 1 week 
before their scheduled UDS. When discussing UDS with the attending urologist, the study will be 
verbally introduced to the patient and a flyer will be provided that includes laymen terms describing 
the protocol, risks and benefits, and information about enrollment.  A phone call (or PatientSite 
message) by the research team will give a brief description of the research study. If the subject 
expresses interest in learning more about the study during the phone call (or in response to the 
PatientSite message), a member of the study staff will confirm eligibility to participate in the study 
based on pre-determined inclusion and exclusion criteria. If they do not qualify for the study, they 
will not be included, and will undergo a standard UDS only.   
If the patient is eligible, informed consent procedures will be initiated using REDCap’s Electronic 
Informed Consent (eIC) platform.  Special care will be taken during the consent process to ensure 
subjects are fully competent and understand the nature of the questionnaires, as well as the 
randomization process (that they will not know at which point in the UDS they will be receiving 
Oxygen rather than SANO). A member of the study staff will review the entirety of the consent form 
and answer any questions before the subject provides a signature. If the subject desires to 
participate in the study, they will be asked to sign the electronic consent form on REDCap (Electronic 
Informed Consent (eIC)).  Subjects will receive an email containing a PDF version of the eConsent 
signed by both the subject and the staff member obtaining the consent. 
 
Efforts will be made to attain a mix of study participants in terms of racial/ethnic representation, 
which is reflective of BIDMC’s patient population and the greater metropolitan Boston area: 63% 
white, 26% African American and 11% other. 
 
Baseline Assessment: 
Confirmation of a patient’s eligibility and completed informed consent will be documented in 
REDCap before proceeding with study procedures. Then, patients will complete the Brief Pain 
Inventory (see attached) via REDCap questionnaire that is sent to the patient’s email. The BPI is a 
well-validated measure that assesses intensity of current pain and interference of pain in the 
patient's life (Dworkin, 2005). If the patient does not complete the BPI electronically before the day 
of procedure, they will be offered the opportunity to complete it on the day of their procedure prior 
to the UDS. 
 
Randomization 

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Study Description – Part B 
CCI Form:  9-2015 
 
 
PI Revision Date:  
December 16, 2022 
 
A UDS is comprised of two phases: a filling phase and a voiding phase.  For the purposes of our study, 
subjects will undergo two “runs”, one with SANO and one with Oxygen.   
Subjects will be randomized to either:  
• Group 1: First run with SANO, second run with Oxygen 
• Group 2: First run with Oxygen, second run with SANO  
The results of the randomization will not be disclosed to patients as part of the study (patient-
blinded), or to the operator of the UDS (provider-blinded). The randomization module in REDCap will 
be used to randomize subjects between the two groups. 
 
The catheters will be placed before the first run, and left in place through the second run (that is, the 
catheters will not be changed between the two runs).  All subjects will receive SANO during catheter 
placement. The UDS will be performed by a BIDMC advanced care practitioner according to usual 
clinical practice. It is standard-of-care for patients to undergo two complete UDS runs:  
• First run: Filling phase, voiding phase (~8 minutes) 
• Second run: Filling phase, voiding phase (~8 minutes) 
 
Therefore, we do not believe the utilization of two runs to be a significant increase in burden on the 
patient. 
 
Pre-procedure Evaluation 
On the day of the UDS, the patient will be brought to the exam room where pre-procedure vitals are 
obtained.  The six-item State Trait Anxiety Inventory and the six-item Pain Catastrophizing Scale will 
be administered to assess patient’s baseline pain and anxiety levels. Information of inhaled gas 
administration and how to self-administer will be explained to the patient using templated verbal 
instructions.  It will be emphasized that if at any point during the procedure, the patient feels 
uncomfortable with the inhaled gas, the team will help remove the mask.   
 
Periprocedural Intervention 
The patient will be moved into the standard procedural positioning in the UDS chair.  Explanation of 
the UDS procedure will be done in the routine manner preferred by the study technician (a Urology 
APP).  An oxygen saturation monitor will be applied to the patient's finger and monitored throughout 
the procedure. The patient’s heart rate will also be monitored. 
 
During the procedure, the patient and their oxygen saturation levels will be monitored by a BLS-
certified MA, RN, APP, or MD (separate from APP performing the procedure). 
 
The inhalation gas mask will be positioned on the patient's face, and the patient will then be 
instructed to begin breathing as previously instructed. Initially, the patient will receive 100% oxygen 
at 10 liters/minute.   
 
After the APP describes the procedure, all patients will have nitrous oxide turned on to 30%, 
ensuring that the patient is relaxed but still conversant through the procedure.  The nitrous will be 
adjusted up or down based on the patient’s response to the question “are you feeling the nitrous” 
and "are you happy at this level”. The range will be between 25 - 45%, and will be recorded. This may 
take 2-3 minutes.  The technician will then insert the urethral pressure catheter as well as the 

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Study Description – Part B 
CCI Form:  9-2015 
 
 
PI Revision Date:  
December 16, 2022 
 
abdominal catheter.  We will then wash out with 100% oxygen for 2 minutes.  We will perform the 
UDS study in the routine fashion, asking the patient to perform routine parameters such as cough, 
report of bladder fullness, and volitionally void.  After the first run, we will again wash out with 100% 
oxygen for 2 minutes while we switch from SANO to oxygen (or vice versa depending on the 
randomization group). 
 
At a single time-point during both runs, the operator handling SANO will ask the patient to complete 
a VAS-A and VAS-P. A laminated sheet will be held in front of the patient, and they will point to a 
number between 1 – 10 to signify their current level of anxiety (VAS-A) and pain (VAS-P). The 
number will be verbally confirmed by the operator handling SANO.  
 
If at any point the patient is unhappy with gas inhalation, the observer will aid the patient in 
removing the mask. At the end of the procedure, the SANO group will be turned down to 0% nitrous 
oxide, and 100% oxygen will be administered through the mask for an additional 2-3 minutes as the 
patient is cleaned and post vitals obtained.  Assessment of the “time in” and “time out” of the 
procedure room will be recorded.   
 
 
Flowchart 1. Intraprocedural Study Activities  
  
Measuring gas flow: 
The maximum flow for this system is 19 L/min. The amount of gas flow is adjusted to match the 
patient’s minute ventilation in order to maintain the black inspiration bag (inhalation reservoir) on 
the Flowmeter about 3/4 full during the procedure.  This varies from patient to patient depending 
upon respiratory rate, and volume of each breath. Excess gas flows through the circuit and into the 
scavenger and has no effect on the patient.  
 
Periprocedural Data Collection   
The APP who performed the procedure will complete an Operator Survey (attached) to assess the 
ease of catheter placement and patient responsiveness during each run.  
After the UDS, the patient will be moved to the recovery room for routine post-procedure vitals as 
well as completion of post-procedure STAI score and Situational Pain Catastrophizing Score (S-PCS) 

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Study Description – Part B 
CCI Form:  9-2015 
 
 
PI Revision Date:  
December 16, 2022 
 
on a tablet computer. The S-PCS was derived from the Pain Catastrophizing Scale (PCS), a validated 
questionnaire used to measure catastrophic thinking associated with pain.  We will also ask if any 
side effects of nitrous oxide were experienced, including nausea, vomiting, dizziness, drowsiness.  An 
additional question of whether the patient feels comfortable driving home independently will be 
assessed.  
 
UDS is generally performed as an outpatient procedure and patients can drive themselves home. In 
our previous study, “Self-Administered Nitrous Oxide (SANO) During Transrectal Prostate Biopsy to 
Reduce Patient Anxiety and Pain” patients were allowed to drive home after study participation, 
without any adverse events or complications. Patients who do not have an escort planned after their 
UDS will be asked to perform two hand-eye coordination tests after completion of post-procedure 
surveys. First, the participants will be verbally instructed to extend one arm in front of them, and 
place one finger to the tip of their nose. After, the Trail-making test Part B will be administered. This 
test has been promulgated by the American Medical Association to screen for driving fitness. The 
Trails-making Part B test will ask participants to connect numbers (1-13) to letters (A-L) randomly 
written on a page. This test is scored according to accuracy and time required to make the 
connections (Joseph, 2013). If the participant is unable to accurately complete these tests, 
additional recovery time will be required. The participant’s performance and disposition will be 
included in the documentation of study procedures performed during the visit. 
 
Following the completion of UDS, each participant will be asked to engage in a structured interview 
with a study team member (see attached interview guide). The interview will be designed to assess 
the experience with SANO during the UDS. It is estimated that the interview will last about 15-20 
minutes. The interview will be conducted in an enclosed patient room in the Surgical Specialties 
clinic on Shapiro 3. As explicitly stated in the informed consent, this interview will be audio recorded. 
Once study recruitment is completed, each interview will be transcribed and coded according to 
predefined thematic framework.  
 
Finally, a chart review will be performed as a safety follow-up to capture any unanticipated ED visits, 
admissions, or office visits for the 7 days following the procedure.  We will also record any phone 
calls that are made by patients within 7 days of procedure that pertain to procedure concerns. 
 
Management of Medical Gases Used in Study 
As the research pharmacy does not procure nor dispense gaseous inhalants, medical gases used in 
the study will be managed per protocol and as per BIDMC’s Compressed Gas Cylinder Storage and 
Handling Policy #: EC-62. Nitrous and oxygen cylinders will be procured through the OR materials 
management specialist. The tanks for study gases will be stored in an approved gas cylinder storage 
rack in (Room 385) of the Shapiro Clinic for immediate usage. There is also a gas tank storage area in 
the Shapiro OR (close to the clinic) for additional storage. Both spaces are secured and locked off 
hours. Research staff will only access these supplies as necessary for the study. 
 

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Study Description – Part B 
CCI Form:  9-2015 
 
 
PI Revision Date:  
December 16, 2022 
 
 
B. 
Statistical Considerations 
Sample Size Justification 
Based on a previous study by Jeon et al, the mean (SD) difference in max cystometric capacity 
(MCC) between repeated UDS fills was 20.6 (11.6) mL. Our sample size calculation to detect this 
difference between repeated fills (p less than 0.05 significance level) was 14 patients per group 
(α=0.05, power=95%). We will inflate out our sample size to account for any missing data or 
withdrawals from the study, such that 25 patients may be enrolled. We aim to randomize 14 
patients in total.  
Data Analysis 
All data will be collected and stored securely using the REDCap system. Data will be managed and 
analyzed by the PI and biostatistical support team at the BIDMC FIRST program.  We will also be 
utilizing the support of outside collaborators, Dr. Scott Wang and Ranveer Vasdev for data 
analyses. Collaborators affiliated with outside institutions will not have access to PHI or any 
identifying information. They will assist with analyses based on de-identified data sent via secure 
electronic transfer. Upon protocol approval, a data transfer agreement will be initiated to allow for 
the transfer.  
Primary outcome measures are patient anxiety and pain levels in the N2O group vs the oxygen 
only group as measured by the VAS and VAS A scores. We are specifically interested in the 
difference in scores between the two groups. Secondary outcome measures include the difference 
in several UDS parameters such as Maximum Cystometric Capacity (MCC), Pdet Max, Detrusor Leak 
Point Pressure (DLPP) Number of Detrusor Contractions, Maximum flow rate (QMax), and Post-
void residual. These measurements will be acquired in the standard method of normal UDS.  
Tertiary outcome measure is operator satisfaction. In each patient group, we will utilize a custom, 
three question survey following each fill-void cycle to assess any difficulty with catheter 
placement, patient responsiveness, and patient procedural tolerance with the following options: 
better than expected, as expected, worse than expected.  
We will also be obtaining a pre- and post-procedure State Trait Anxiety Inventory (STAI) and Pain 
Catastrophizing Scale (PSC) and post-procedure Situational Pain Catastrophizing Scale on all 
participants and compare the variation in response. Operator ease in performing the UDS will be 
measured by 3 simple questions assessing patient positioning and ease of catheter insertion.  
Lastly, the structured interview will be analyzed according to a predefined qualitative framework 
to guide how our transcripts will be coded for final data analysis.  
 

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Study Description – Part B 
CCI Form:  9-2015 
 
 
PI Revision Date:  
December 16, 2022 
 
C. 
Subject Selection 
Subject Population 
The study population will be all patients aged 21 to 85 years referred for UDS within the BIDMC 
Division of Urologic Surgery. A total of 14 patients will be enrolled for the study. 
Eligibility Criteria 
Inclusion criteria:  
(1) Scheduled for UDS 
(2) Aged 21 to 85 years  
(3) No learning disabilities  
(4) Suitable for nitrous oxide/oxygen IHS with willingness to undergo two UDS runs during the 
procedure  
(5) Access to an email and computer 
Exclusion criteria:  
(1) Perioral facial hair impeding good mask seal 
(2) Learning disabilities and/or inability to cognitively complete survey questions 
(3) Has any of the following medical conditions:  
a. Inner ear, bariatric or eye surgery within the last 2 weeks,  
b. Current emphysematous blebs,  
c. Severe B-12 deficiency,   
d. Bleomycin chemotherapy within the past year, 
e. Heart attack within the past year, 
f. Stroke within the past year,  
g. Class III or higher heart failure.  
  
 
 
B4. 
POSSIBLE BENEFITS 
We do not anticipate that subjects will directly benefit from participation. Patients receiving SANO 
may potentially experience decreased pain and anxiety when undergoing catheter placement.   
Taking part in the study will increase scientific knowledge regarding the ability to use SANO as a 
means to decrease stress and anxiety for patients undergoing UDS, and still obtain similar 
outcomes when compared with oxygen. This may specifically benefit those patients who have prior 
poor experience with UDS yet need repeat studies, such as in pediatric patients. 
 
 

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Study Description – Part B 
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PI Revision Date:  
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B5. 
POSSIBLE RISKS AND ANALYSIS OF RISK/BENEFIT RATIO 
Risks related to the use of questionnaires  
Minimal risks associated with the completion of questionnaires include subject fatigue and the 
possibility of increased anxiety in answering questions about baseline pain and pain related to the 
procedure.  Subjects will be informed that they are free to discontinue their participation in the 
study at any time should they choose. 
Risks related to Nitrous Oxide administration 
Nitrous oxide is a well-known drug used in medicine for anesthetic and analgesic purposes.  Its use 
during labor has been shown to be safe and effective, with no known long-term effects on the 
mother and no known effects on the infant.  There are known long-term effects of environmental 
exposure to nitrous oxide, including infertility, when not using a scavenger system for the escaped 
environmental nitrous oxide.  The Miniscav® nitrous waste gas evacuation pump has been FDA-
approved for use in medical offices with the Nitrouseal® system.  We will be using the Nitrouseal® 
and Miniscav® nitrous waste gas evacuation pump in the same way that has already approved by 
the FDA. 
Nitrous oxide does have a risk of nausea and vomiting.  The reported rates have been as high as 
13% in literature; however, these are at higher concentration of nitrous oxide and with longer 
durations.  The reported vomiting risk with the Nitrouseal® system is <0.5%.   For the procedure, 
the patient is maintained in the lateral position, which should minimize any aspiration 
risk.  Sweating, drowsiness, lightheadedness, tachycardia and facial flushing has also been 
reported.  The patients are routinely monitored after the UDS, and any ill effects of the procedure 
itself or of the nitrous oxide will be assessed and cared for by our study team and clinical staff.   
Approximately 5-10% of patients who undergo UDS at BIDMC exhibit dizziness or vasovagal 
response during the procedure. This risk is solely attributed to the nature of UDS. Due to the rapid 
offset of SANO (2-3 minutes), we do not believe this risk to be compounded after receipt of SANO. 
According to standard clinical practice, the APP performing the UDS and the SANO administrator 
will take special care to ensure a patient is stable and able to ambulate safely after catheter 
removal and completion of the UDS.  
Finally, as with any inhaled gas, there can be a concern of hypoxia or apnea with administration of 
nitrous oxide. This event has not been routinely reported in the literature as a risk or side effect of 
nitrous oxide. During the procedure, patients will undergo continuous oxygen saturation and heart 
rate monitoring. These values will be documented in REDCap as part of the patient’s study records.  
If there are concerns of hypoxia, either objectively by the oxygen monitoring or subjectively by the 
patient, the protocol will be to immediately turn off the nitrous oxide and administer 100% oxygen 
until vitals return to baseline.  All personnel in the room will have BLS training.  The Clinical 
Research Center has a code cart which is readily available. e  proximate to areas  

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Study Description – Part B 
CCI Form:  9-2015 
 
 
PI Revision Date:  
December 16, 2022 
 
Possible Unauthorized Use of Nitrous Oxide 
Inhalation of nitrous oxide is used/abused in recreational settings with the purpose of causing 
euphoria and hallucinations.  To prevent potential misuse, the nitrous oxide will be stored within 
the operating room storage area reserved for anesthetic gases during non-office hours.  
Potential for Loss of Confidentiality  
There is a potential for loss of confidentiality for participants in the study. Protections will be 
implemented to mitigate this risk. As detailed in our protocol, we will use REDCap to collect patient 
information and questionnaires.  Though REDCap is generally considered secure for the purposes 
of PHI, it is a web-based application and the data is accessible to study team members on their 
own personal computers.  Access to our REDCap will be limited to study team members who are 
trained in protecting PHI. Any electronic study files or information that is not stored on REDCap will 
be kept on a secure directory on the BIDMC server that is only accessible to research staff. 
Only summaries of group data will be reported in any publications or presentations, and will not 
contain any identifying information. These precautions will protect PHI in accordance with HIPPA 
regulations.  
Reporting of Adverse Events 
All adverse events will be reported to the BIDMC Human Research Committee promptly in 
accordance with guidelines. 
Analysis of Risk/Benefit Ratio 
Based on the above risks, the principal investigator views this study as moderate risk. With the 
precautions and procedures to minimize risk as described in this section, we anticipate minimal 
complications and discomfort. In light of the study’s potential benefits, the principal investigator 
believes the risk:benefit ratio to be favorable. 
 
B6. 
RECRUITMENT AND CONSENT PROCEDURES 
Recruitment 
 
The primary Urologist will introduce the SANO-UDS study to the patient at the time the UDS 
procedure is discussed. After the Urologist has discussed and planned for UDS, the study team will 
examine the list of scheduled UDS patients for the week, and a baseline examination by the clinical 
team for eligibility verification will be performed through a medical record review by a trained 
member of the research staff.  
Patients who meet criteria will be reviewed by their Urology Attending who will provide 
authorization to contact eligible subjects.  Then, patients will be sent a secure message via 
PatientSite (See Template Introductory Letter) to introduce the study.  In addition, the patient will 
be called on their preferred clinical contact phone number by a study team member.  The study 
team member will follow a templated introductory contact script (See Template Introductory 
Contact Script).  In attempting to reach the patient, and in accordance with BIDMC Human 

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Study Description – Part B 
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PI Revision Date:  
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Research procedure, no more than ten (10) phone attempts will be performed, and all calls will 
take place between 10am-9pm Monday through Friday, and 10am – 5pm Saturday and Sunday. If 
there is no answer, study team member will leave a templated contact script (See Template No 
Answer Contact Script).  
 
In the event that individuals contacted are distressed in any way by the contact, we will contact 
the patient's Urology Attending, who will either personally reach out to the patient to alleviate 
their concerns or have a designated team member reach out to the patient to alleviate their 
concerns. 
Consent 
Informed consent will be obtained for all participants who are potential study candidates. A 
qualified member of the research team will review the informed consent form with all patients 
who express interest in the study. The subject will be allowed to ask questions at any point. Study 
personnel will explain that the subject is free to refuse participation in this research study and that 
participation does not affect their scheduled procedure, nor their relationship with their providers 
at BIDMC. All patients who agree to participate will be asked to sign the ICF electronically through 
REDCap if they have access to a computer. Consent will be obtained before any study-specific tests 
or procedures are performed. If participants do not have access to email or smart device, written 
consent will be obtained on the day of their UDS, prior to being taken to the procedure room. 
Study personnel will document the consent process. Subjects will be provided with an electronic 
copy of the signed ICF if obtained via REDCAP electronic consent, or a copy of the print consent 
form. 
Subject Protection 
As subjects in the study may be patients of study investigators, measures will be taken to prevent 
coercion and undue influence. The study team will emphasize that participation is voluntary and 
will not impact their relationship with any individual at BIDMC. Investigators will be trained to 
conduct consent in a manner that does not lead to coercion and undue influence.  
 
B7. 
STUDY LOCATION 
Privacy 
 
The study will be conducted on the premises of BIDMC Longwood Campus.  We will obtain lists of 
patients intended for UDS, and study team members will review the OMR records for inclusion and 
exclusion criteria.  The patient will be contacted by phone either from in-office phone call or 
through Doximity phone application (which provides the BIDMC Urology office as the caller 
ID).  We will ask the patient whether they are in a location that affords privacy for discussion of 
medical information.  If they are not, we will arrange an appropriate time when the patient will 
have privacy for study discussion.   Phone interviews by study team members will be conducted in 
private space to avoid the interview being overheard. 
 

(CCI) Committee on Clinical Investigations 
Page 14 of 15 
 
Study Description – Part B 
CCI Form:  9-2015 
 
 
PI Revision Date:  
December 16, 2022 
 
Pre-procedure questionnaires will be emailed to private patient email via the REDCap server.  Data 
collected will be kept within the REDCap server.  Access to our REDCap will only be allowed for 
study team members who are trained in protecting PHI. 
 
Operator Surveys will be on paper forms with patient identifying sticker on the form.  At the end of 
the UDS, the data will be input into the REDCap system by a study team member, and the paper 
version will be stored within each subject’s file. 
 
Pre-procedure and post-procedure STAI, PCS, VAS, VAS-A score, Situational Pain Catastrophizing 
Score (S-PCS) and Trails-making Part B tests will be obtained in a private exam room where only 
the patient, study team members, and clinical staff measuring vitals will be present.  Questionnaire 
answers will be input by the patient into a tablet computer.  The tablet computer will be wiped 
with sanitizing wipe between uses. 
 
Physical Location 
 
The UDS procedure itself will take place in the Clinical Research Center, Room ST 802 (“infusion 
room”). The structured interview will also take place in the Clinical Research Center, but in a 
different enclosed patient room than where the UDS was done. Medical record reviews will occur 
at a secure workstation at BIDMC or through BIDMC’s VPN server. 
The nitrous tanks will be stored in an approved gas cylinder storage rack in (Room ST 802) of the 
Clinical Research Center for immediate usage. Both spaces are secured and locked off hours.  
 
 
B8. 
DATA SECURITY 
All OMR access and assessment will be performed on the BIDMC server using the BIDMC firewall. As 
detailed in our protocol, we will use REDCap to collect patient information and questionnaires. Input 
of PHI data into the REDCap system by team members will only be through the BIDMC server using 
the BIDMC firewall.  Access to our REDCap will only be allowed for study team members who are 
trained in protecting PHI.  Only summaries of group data will be reported in any publications or 
presentations, with no identification of individuals.  
Operator Surveys will be on paper forms with patient identifying sticker on the form.  At the end of 
the UDS, the data will be input into the REDCap system by a study team member, and the paper 
version will be disposed of in a disposal unit intended for medical information waste. 
 
B9 
Multi-Site Studies 
 
Is the BIDMC the coordinating site?       
 Yes    
 No  
 
Is the BIDMC PI the lead investigator of the multi-site study?     
 Yes    
 No  
 

(CCI) Committee on Clinical Investigations 
Page 15 of 15 
 
Study Description – Part B 
CCI Form:  9-2015 
 
 
PI Revision Date:  
December 16, 2022 
 
B10 
Dissemination of Research Results 
Participants will be thanked for their participation in the research study. Results of research 
conducted through this protocol will be published in peer-reviewed journals and presented in 
scientific conferences. No identifiable information will be published or presented 
 
References 
 
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children undergoing voiding cystourethrography and does not interfere with the diagnosis of 
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Merguerian PA, Corbett ST, Cravero J. Voiding ability using propofol sedation in children 
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Collins, M OGNN - Use of Nitrous Oxide in Maternity Care: AWHONN Practice Brief Number 6. 
Journal of Obstetric, Gynecologic, and Neonatal Nursing Mar 2018 (239-242) 
 
Clark, M. S., & Brunick, A. L. (2020). Anatomy and Physiology of Respiration and Airway 
Management. In Handbook of Nitrous Oxide and oxygen sedation (pp. 74–74). essay, Elsevier. 
 
 
Bringman H, Giesecke K, Thorne A, Bringman S. Relaxing music as pre-medication before 
surgery: a randomised controlled trial. Acta anaesthesiologica Scandinavica. 2009;53(6):759-764.  
 
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