Reduction of Bladder Injection Pain With Belladonna Opiate Suppository: A Randomized, Double-Blind, Placebo-Controlled Trial (ROBIN Trial)
Phase: PHASE4
Conditions: Overactive Bladder, Urinary Urge Incontinence, Urinary Bladder, Neurogenic, Painful Bladder Syndrome
Sponsor: Edgar LeClaire, MD

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Official Title of Study: Reduction of Bladder Injection Pain with 
Belladonna Opiate Suppository: A Randomized, Double-Blind, 
Placebo-Controlled Trial (ROBIN Trial) 
 
NCT Number: NCT02600715 
 
Document Date: 5 November 2015 
 
Wichita Medical Research and Education Foundation IRB 
Approval Date: 9/16/2015 
 
University of Kansas Medical Center IRB  
Approval Date: 11/6/2015 
 

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Title 
Reduction of Bladder Injection Pain with Belladonna Opiate Suppository: A 
Randomized, Double-Blind, Placebo-Controlled Trial (ROBIN Trial) 
 
Version Date: 5 November 2015 
 
Principal Investigator: Edgar LeClaire, MD 
 
Co-Investigators: Rachel Wykes, MD, PGY-3, Jennifer Duong, MPH 
 
 
Clinical Site: Wichita Women’s Pelvic Surgery Center at Associates in Women’s Health 
 
Introduction, Background, Study Rationale 
 
Introduction 
Overactive bladder (OAB) and urge urinary incontinence (UUI) affect 17% of women in 
the United States [1]. The economic burden of these conditions is estimated at well over 
$24 billion and is expected to increase [2, 3]. Moreover, the devastating impact on 
patients who suffer from OAB and UUI are well established. Clear associations with 
depression, sleep disorders, sexual dysfunction, and decreased quality-of-life scoring 
on validated surveys have all been observed in epidemiologic studies [4]. 
 
Bladder injection with Onabotulinumtoxin A (BoNT), also known as Botox (Allergan ®), 
is an effective, Food and Drug Administration (FDA) approved for the treatment of OAB 
and Neurogenic Bladder (NB) (also known as neurogenic detrusor overactivity) that has 
failed first-line medical management. Additionally, the American Urologic Association 
endorses BoNT bladder injection for the treatment of refractory Painful Bladder 
Syndrome (also known as Interstitial Cystitis) [5, 6]. Bladder injections with BoNT may 
be done under general anesthesia in operating room settings. However, BoNT 
treatment is increasingly performed as an office procedure [7]. The safety and efficacy 
of BoNT injection for the treatment of bladder symptoms has been well established [7, 
8]. Studies have assessed overall patient satisfaction with BoNT treatment results, but 
not specifically pain or discomfort during the procedure [9, 10]. 
 
Currently, trans-urethral lidocaine gel and bladder instillation of lidocaine-bicarbonate 
solution is recommended as standard analgesia for office injection of BoNT during 
cystoscopy [11, 12]. While this regimen allows relatively painless instrumentation of the 
urethra, evidence supporting its efficacy is lacking [13]. Furthermore, the experience of 
BoNT injection providers suggests standard analgesia is inadequate for controlling 
bladder injection pain. Pain experienced during the procedure may deter subsequent, 
cost-effective, office treatments. Bladder injection pain experience has not been 
substantively addressed in the literature.  
 
Belladonna & opiate (B&O) suppositories have been commonly used to treat spastic 
lower urinary tract pain. This medication contains a naturally occurring plant alkaloid 
derivative which relaxes the bladder and an opioid analgesic such as opium or 

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morphine. B&O suppositories have been investigated in robotic prostatectomy studies 
that demonstrating diminished need for IV analgesia and improved post-op pain control 
[14, 15]. The most common version of the B&O suppository is comprised of belladonna 
and opium. The B&O suppository that will be used in this particular study will be 
belladonna and morphine, in which the morphine will be the pharmacologic equivalent 
of opium. The belladonna and morphine suppository is a commonly used and is 
pharmacologically equivalent to other belladonna and opiate suppositories. For the 
remainder of the protocol, B&O suppository will be used to generically reference 
belladonna and opiate suppositories unless otherwise stated. 
 
This randomized trial is designed to assess the effectiveness of B&Os as an adjunct to 
standard analgesia for improved BoNT injection pain. 
 
Background 
Overactive bladder (OAB) and urge urinary incontinence (UUI) affect 17% of women in 
the United States [1]. The economic burden of these conditions has been estimated at 
well over $24 billion and is expected to increase to nearly $82.6 billion in 2020 due to 
the aging population [2, 3]. These costs are largely due to the routine management of 
the symptoms (i.e. pads). Treatment costs account for a mere 14% of the overall cost. 
Cost reduction measures may include increasing access to diagnosis and treatment of 
OAB.  Furthermore, the devastating impact on patients who suffer from OAB and UUI 
are well established. Clear associations with depression, sleep disorders, sexual 
dysfunction, and decreased quality-of-life scoring on validated surveys have all been 
observed in epidemiologic studies [4]. 
 
OAB is defined as urgency, with or without urge incontinence, usually with frequency 
and nocturia [16]. This affects up to 17% of women. The mechanisms contributing to 
urge incontinence include intrinsic malfunction of detrusor (bladder wall muscle) activity, 
overstimulation of detrusor muscle by acetylcholine, sensory urgency caused by 
abnormal sensory processing, or abnormal neuronal input to the detrusor. First line 
treatment involves bladder training, with the addition of oral anti-muscarinic agents if 
needed. Theses oral therapies improve symptoms and quality of life, with the NNT of 5-
9 [17]. Albeit effective, these medications have reportedly poor adherence due to side 
effects with as many as 83% of patients discontinuing medication within the first 30 
days. Second-line management includes BoNT intravesical injections, percutaneous 
posterior tibial nerve stimulation, and percutaneous sacral nerve stimulation. BoNT is 
one of the safest, least invasive, and effective options for refractory OAB [18]. 
 
Neurogenic bladder (NB), also known as neurogenic detrusor overactivity (NDO) is the 
urodynamic finding of uncoordinated bladder contractions. Those most commonly 
affected are young males with spinal cord injury and young females with multiple 
sclerosis.  Of the estimated 273,000 people in the US with spinal cord injury, 81% 
experience urologic symptoms [19]. Additionally, 50-90% of persons with MS; 50% of 
persons with diabetic neuropathy; 24% of those with brain tumors; and 50% of patients 
with spinal stenosis will experience NB [20]. Among cerebrovascular accident sufferers, 
8-11% will experience NB symptoms [21]. For NB patients who are able to empty their 

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bladder, oral medication in the form of anticholinergics. BoNT injection into the bladder 
has been shown to reduce the frequency of urinary incontinence episodes and daily 
urinary frequency at 4-6 weeks and 12 weeks following the injection [22]. Thus, BoNT 
injection is indicated for patients who fail first-line therapy with oral anticholinergics. 
 
Onabotulinumtoxin A (BoNT) is a neuromuscular blocking agent acting on the 
presynaptic membrane of the neuromuscular junction, preventing calcium dependent 
release of acetylcholine. FDA-approved indications include treatment of urinary 
incontinence caused by detrusor overactivity due to a neurologic condition and 
treatment of overactive bladder (OAB) (including symptoms of urge urinary 
incontinence, urgency, and frequency) in adults who show inadequate response to oral 
medication or do not tolerate the common side-effects of first-line anticholinergics (i.e. 
dry-mouth, constipation, confusion). The American Urologic Association also endorses 
BoNT bladder injection for the treatment of refractory Painful Bladder Syndrome (also 
known as Interstitial Cystitis) [5, 6]. In terms of effectiveness, study participants 
undergoing BoNT treatment experienced a 3-4 fold reduction in daily incontinence 
episodes compared placebo. A treatment effect size of this magnitude has not been 
demonstrated with first line agents (anticholinergics or beta-3-agonsits) [23]. Studies 
repeatedly reinforce the safety and efficacy of BoNT at doses of 100-200U administered 
10-30 sites [7, 8]. BoNT treatment has also demonstrated improved quality of life 
measures 6 weeks following injection and improved sexual function in women with MS 
[24, 25].Studies have established the effective dosage of BoNT at 100-200 units, 
injected in 1 to ½ unit increments throughout the bladder wall (totaling 10-20 injections 
per treatment) [7, 8].  
 
BoNT is well tolerated and most common adverse events are limited to transient 
urologic conditions; urinary tract infection (UTI) and urinary retention (the latter in dose 
dependent fashion). UTIs have been reported in 2-32% of patients after initial treatment. 
The risk of urinary retention occurs in 6-17% of patients and may present in days or 
weeks following injection and can last up to 12 weeks. Thus, patients must be willing 
and capable of performing intermittent self-catheterization should retention occur. 
Contraindications to BoNT injection are reviewed in Table 1 [3, 11, 24].   
 
Table 1. Contraindications to BoNT injection of the bladder 
 
Presence of infection at proposed injection site 
 
Known hypersensitivity to BoNT toxin preparation or any components in the 
formulation 
 
Urinary tract infection 
 
Urinary retention 
 
Post void residual > 200ml in patients NOT routinely performing clean 
intermittent self-catheterization (CISC) 
 
Patient unwilling or unable to use CISC 
 
Patient unable to discontinue anti-platelet therapy for 3 days prior to injection 
 
Anti-coagulation therapy that cannot be adjusted for the procedure 
 
Non-compliance with prophylactic antibiotics 
 
Onset of action is 2-4 weeks with and expected treatment duration of 42-48 weeks.  
Injection can be repeated as needed as soon as 12 weeks after injection. Clinical follow-

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up is recommended 1-2 weeks following the procedure and again at 2-3 months [26, 
27].  
 
BoNT injection of the bladder can be performed under general anesthesia, but in its 
most cost-effective form it is administered an in-office procedure [7]. Though studies 
have evaluated patient satisfaction with results of in-office treatment, limited data exist 
to guide optimum pain management during injection [9, 10]. 
 
B&O suppositories (NDC-054-7045-12 and NDC-0574-7040-12, Case# 665219) have 
been commonly administered to treat spastic lower urinary tract pain.  B&O combines 
the anti-muscarinic properties of a naturally occurring plant alkaloid derivative to relax 
the bladder with opioid analgesia. B&O suppositories have been used safely in robotic 
prostatectomy studies and have demonstrated diminished need for IV analgesia and 
improved post-op pain control [14, 15]. B&O suppositories have not been studied for 
pain control during urogynecologic office procedures, although they are frequently 
utilized in office procedure analgesia protocols.   
 
The antimuscarinic (anticholinergic) effects of belladonna alkaloid are dose dependent 
and include relaxation of smooth muscle, bronchodilation, pupil dilation, decreased 
gastric motility, transient tachycardia, and, most significant for this study, decreased 
tone and amplitude of ureteral and bladder contractions. B&O suppositories pair the 
belladonna anti-spasmotic with analgesia of an opioid to minimize discomfort associated 
with ureteral spasm. B&O suppositories have been used safely in robot assisted 
laparoscopic prostatectomy studies [15]. Administration of B&O suppositories prior to 
urologic procedures has been shown to decrease IV pain medication requirements and 
overall pain postoperatively [14]. The common B&O suppository formulation contains 
16.2mg Bella Donna and 30 or 60 mg of opium and may be dosed as 1 suppository 1-4 
times a day. The cost of this medication is approximately $400 for 12 tabs. 
Contraindications to this medication include hypersensitivity to belladonna, opiate, or 
any component of the formulation; glaucoma; severe renal or hepatic disease; bronchial 
asthma; respiratory depression; convulsive disorders; acute alcoholism; premature 
labor.  Adverse reactions occur with an undefined frequency but may include 
palpitations, dizziness, drowsiness, pruritus, urticarial, constipation, nausea/vomiting, 
zerostomia, urinary retention, blurred vision, photophobia.  The anti-cholinergic effect of 
BoNT, when therapy administration is closely monitored, is not likely since a single B&O 
dose will have worn off long before the 2-4 week onset period of BoNT is complete. 
Minimal systemic effect has been noted with suppository administration. Additionally, 
patients undergoing this therapy have theoretically already withstood an anticholinergic 
trial as a first line treatment for OAB/NB [28, 29]. 
 
Study Rationale 
Data are lacking to demonstrate the ideal pain control regimen during office injections of 
BoNT. This is likely due to the relatively new application of this procedure in office.  One 
study comparing average pain during intravesicle injections with use of alkalinized 
lidocaine vs lidocaine gel demonstrated no result [13].  Additionally, it is difficult to 
accurately represent the patient pain experience. The Numeric Rating Scale (NRS) is a 

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valid and reliable measure of pain intensity [30]. The primary outcome of our study will 
be determined by the patient experience objectified with the NRS.  The overall goal of 
this study is to improve the patient experience with cost-effective evidence-based 
treatment.  
 
Research Plan and Design 
 
Study Objectives 
The primary objective is to determine the effectiveness of B&O suppositories in 
decreasing bladder injection pain at time of BoNT injection. 
 
Our null hypothesis: Among patients given standard analgesia for BoNT treatment of 
overactive bladder (OAB), neurogenic detrusor overactivity (NDO), or refractory 
interstitial cystitis (IC), there is no difference in bladder injection pain scores with the 
addition of B&O suppository when compared to placebo suppository. 
 
H0: Mean ∆ pain during procedure in active suppository group = mean ∆ pain during 
procedure in placebo suppository group. 
 
Change in pain (Mean ∆ pain) is considered to be the difference in pain from the 
baseline pain level after analgesia, and after the first 10 injections. 
 
Outcomes 
The primary outcome will be bladder injection pain. Pain will be measured using 
numeric rating scales (NRS). Participants will score their preoperative baseline pain 
level when they check into the clinic for their procedure (Po). Participants will report pain 
40 minutes after administration of standard analgesia and suppository (just prior to 
bladder injection) (Pa). This will allow calibration of our primary outcome for patients with 
higher levels of baseline pain not related to the procedure (using themselves as 
controls). They will then be asked to rate bladder pain after the first 10 injections 
(midpoint of the procedure) intraoperatively (P10). After the procedure is completed, 
which would be after 20 injections, the patient will again be asked to report their pain 
(P20). 
 
The operational definition of our primary outcome will be calculated difference in NRS 
pain score prior to procedure (Pa) and midway through procedure (P10): ∆ pain 
(intraoperative pain score – preoperative pain score). 
 
Secondary outcomes will include: pre-analgesia pain score (Po), post-operative pain 
score (P20), patient intolerance to the procedure, postoperative voiding trial results (pass 
/fail), and post void residual (PVR) results at 2 week follow-up (measured in ml, 
pass/fail), and diagnosis of urinary tract infection (accepted clinical definition of acute 
cystitis or a positive urine culture) at 2 week follow-up. PVRs < 200ml at 2 week follow-
up will be considered passing result [31]. 

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Participants will also rate their level of satisfaction with pain control immediately after 
the procedure using a simple Likert scale. This will be a 4-level scale ranging from ‘not 
at all satisfied,’ ‘slightly satisfied,’ ‘mostly satisfied,’ and ‘very much satisfied.’  
 
Expected Results 
Investigators believe that participants randomized to the B&O suppository group will 
experience less bladder pain (average pain) during the BoNT injection procedure than 
those that were assigned to the placebo group. 
 
Study Type and Design 
This study is a randomized, pilot trial. Clinical investigators and participants will be 
blinded to the randomization groups. Participants, whom have elected to receive BoNT 
injection therapy, will be randomized to receive either a placebo or B&O suppository 
prior to the procedure. Pain will be accessed prior to the procedure, during the 
procedure, and after the procedure. 
 
Sample size 
Sample size is calculated assuming the group receiving the B&O suppository reports an 
average intra-procedural pain (P10) score of 4.5, and assuming the control group 
(placebo) reports an average intra-procedural pain (P10) score of 8. The assumed 
standard deviation is 3. Based on a power of 0.8, the required sample size per 
randomization group is 13. The total sample size required to achieve a power of 0.8 for 
this pilot trial would be 26 (13 per group). 
 
Randomization 
Eligible participants will be assigned with equal probability to one of two treatment 
groups: belladonna and opiate (B&O) suppository and inactive placebo suppository. 
Block randomization will be utilized to maintain balance between study group sizes over 
time and to enhance blinding of the clinical investigators; a repeated run of placebo or 
active suppositories may lead to an anticipatory bias effect on subsequent participants. 
An online randomized block generator will be utilized. Block size will be randomized and 
will not be revealed to clinical investigators. As the proposed study is double-blinded, 
selection bias is unlikely. 
 
Study drug suppositories will be randomized in sequential pill canisters. Aside from 
standard indications to do otherwise, treatment allocation will remain concealed until 
enrollment and follow-up visits have been completed.  
 
Working with the compounding pharmacy, an unblinded data coordinator will label, and 
track, the active and placebo drug assignments. Once the patient has consented to 
participate in the study, the Principal Investigator will assign the participant sequentially, 
and will notify the data coordinator and compounding pharmacy. Based on a sequential 
numbering system, the participant will be randomized to receive either the B&O 
suppository or the inactive placebo suppository based on the block assignment. The 
Principal Investigator will complete an authentic prescription in order to comply with all 
Drug Enforcement Administration (DEA) requirements for securing Schedule 2 

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narcotics. The prescription will be provided to the compounding pharmacy, which will fill 
the prescription based on the pre-determined randomization scheme. The compounding 
pharmacy will document and deliver the pill canister matching the participant’s ID 
number, to the clinic and provide it to the Principal Investigator to store in a locked 
medicinal refrigerator in a locked room until the day of the procedure. Prior to 
administering the suppository to the patient during the procedure, the Principal 
Investigator will open the pill canister and document the pill canister number and the 
number labeled on the suppository in the patient’s medical record, and study 
documents. If unveiling the randomization for a participant is required, the Principal 
Investigator can call the data coordinator or the compounding pharmacy, and the 
coordinator or the lead pharmacist will reveal the participant’s randomization 
assignment over the phone. Monthly meetings will be conducted to audit the enrollment 
and to ensure randomization procedures are conducted appropriately. 
 
Statistical Analysis 
Preoperative demographic variables including age, race, parity, body mass index 
(kg/m2), menopausal status, smoking status, medical comorbidities, and indication for 
BoNT treatment (OAB vs. NDO) will be compared between active and placebo patients. 
Continuous variables will be compared using Student t-tests. Categorical variables will 
be described as frequency data (proportions & percentages) and compared using Chi-
square or Fisher’s exact test (when expected values in any cell are less than 5). Ordinal 
variables will be compared using Wilcoxon Rank Sum tests. 
 
An intent-to-treat analysis approach will be used. Results for the active group versus the 
control group will be compared with paired t-tests if the data are normally distributed 
and with Mann-Whitney tests if the data are skewed. Regression modeling will be used 
to analyze the relationship between our primary outcome with the following predictor 
variables; active vs. placebo, indication for BoNT injection (OAB vs. NDO), demographic 
variables, and pain scores (before-during-after procedure). Interactions between 
variables will be assessed and, if significant, included in the model.  
 
Confounding variables will be included in the model if point estimates change by more 
than 20% with their inclusion. Continuous variables will be assessed for linearity and 
converted to categorical variables as indicated by model fit statistics (c-statistic, 
Deviance, Pearson, Hosmer-Lemeshow). Cochran-Armitage and Goodness of Linear 
Fit tests will be used to evaluate for linear trends between suppository treatment and 
our primary outcome.  
 
All statistical analyses will be two-sided. P-value of less than 0.05 is considered to be 
statistically significant. An interim analysis will be performed one year after Institutional 
Review Board if the study has not completed data collection within one year. Results 
will not be given to participants.  
 
 
 

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Participants 
Patients will be approached for participation once they have selected BoNT therapy for 
treatment of overactive bladder (OAB), neurogenic detrusor overactivity (NDO), or 
refractory interstitial cystitis (IC).  
 
To be included in this study, patients must be 18 years old or older at the time of the 
informed consent discussion, have met clinical criteria under outside care or during the 
Principal Investigator’s routine standard of care for BoNT injection therapy (failed initial 
medical management), and there must be no contraindication to BoNT therapy as 
outlined by drug manufacturer guidelines (Table 1). Patients will have elected to have 
the BoNT injection therapy prior to being offer enrollment into the study for either OAB, 
NDO, or IC. 
 
Patients will be excluded for pregnancy, currently nursing a baby, age less than 18 
years, or anticipated geographic relocation within the first 3 months following treatment. 
Patients will be excluded if the patient reports an allergy to morphine, belladonna, or 
opiates. Patients will also be excluded if participating in another research study. 
Individuals unable to provide informed consent or to complete two-week follow-up 
bladder testing (post-void residual) or data collection will also be excluded. Prior to 
randomization, a data coordinator will verify eligibility and completeness of baseline 
data. 
 
Participants will be withdrawn or terminated from participating in the study by a clinical 
investigator if they fail to undergo the BoNT injection procedure and do not reschedule 
before the conclusion of the study. 
 
Potential confounding factors will be considered and treated appropriately during the 
statistical analysis. Additional confounding factors such as variability in pain and 
narcotic usage will be discussed in the manuscript. Investigators do not anticipate 
potential confounders will significantly affect the results of the study. 
 
Standard of Care Procedures 
All participants will receive injection with BoNT (Botox, Allergan) as standard clinical 
care. OAB participants will receive 100 units and NDO participants will receive 200 units 
per FDA guidelines. All participants will also undergo standard recommended 
preoperative analgesia per manufacture guidelines, intravesical instillation of 2% 
lidocaine (60ml) + sodium bicarbonate (10ml), administered 40 minutes prior to 
cystoscopic bladder injection. Viscous lidocaine will be used to anesthetize the urethra. 
 
BoNT will be prepared and injected per manufacturer guidelines. After reconstitution in 
10ml of normal saline, BoNT is injection in 0.5ml increments (20 injections total) into the 
detrusor muscle layer of the bladder dome in a standardized square pattern (Figure 1).  
Injection pattern will also not differ from clinical standard practice, and all patients 
receive the same, trigone sparing injection pattern [32]. 
 
 
 

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Figure 1.Bladder injection pattern. 
 
 
 
Regardless of participation, patients will undergo the injection procedure with BoNT, 
and will receive the analgesia per standard of care, both of which will be billed to the 
patient’s insurance company. Costs associated with the BoNT therapy, including the in-
office procedure visit, follow-up visit, physician fees, bladder testing conducted during 
two weeks follow-up, and any additional follow-up care, will be billed to the patient’s 
insurance company, or will be the responsibility of the patient. 
 
Information regarding volume of BoNT used in the procedure, as well as analgesia 
information will be collected for research purposes. Voiding trial samples, if clean, will 
be discarded as standard office procedures. If an infection is present, the sample is sent 
to the lab as standard office procedures required for appropriate medical management. 
 
Research Intervention 
Participants randomized to the active group will receive a rectal belladonna & opiate 
(B&O) suppository along with standard analgesia 40 minutes prior to bladder injection.  
 
Participants randomized to placebo will also receive standard analgesia as well as a 
rectal suppository composed of inactive base 40 minutes prior to bladder injection. 
 
Study drug will be provided by a compounding pharmacy (Custom Rx Pharmacy and 
Wellness Concepts (3510 N. Ridge Road, Suite 900, Wichita, KS, USA) that can 
produce visibly identical active and placebo suppositories. Dosage of the compounded 
active suppository is belladonna 16.2mg and morphine 7.5mg, which matches the 
commercially available belladonna and opium suppositories (belladonna 16.2mg + 
opium powder 60mg). Compounded belladonna dose will be the same (16.2mg) and 
morphine equivalent dose (7.5mg) will be used in place of powdered opium component. 
Using morphine, which carries a Schedule 2 narcotics classification, requires adhering 
to  DEA restrictions for compounding purposes. The Principal Investigator will write an 
authentic prescription for each participant enrolled in the study (each prescription will 
refer to the research study, and will request “B&O suppository or placebo”), which will 
assist with adhering to guidelines for using Schedule 2 narcotics in clinical practice. 
Blinding afforded by using similar suppositories also enhances study rigor. 

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The B&O suppository and placebo pills participants receive will not be billed to the 
patient’s insurance company. 
 
Origin, Tracking, and Dispensing of Suppositories 
The placebos and B&O suppositories will be purchased from Custom Rx Pharmacy and 
Wellness Concepts (3510 N. Ridge Road, Suite 900, Wichita, KS, 67205).  
 
The pharmacy will compound belladonna and morphine suppositories (16.2mg/7.5mg) 
to the same dose equivalent of opium (60 mg). Compounding the belladonna and 
morphine (morphine sulfate 7.5 mg is approximately equivalent to powdered opium 60 
mg) would be more feasible for the study than using commercial B&O suppositories 
because the pharmacy cannot duplicate the exact size and shape of the commercially 
available B&O suppositories for research purposes. Due to the research being double-
blinded to the participant and the investigators, compounded belladonna and morphine 
suppositories will be used. Compounded belladonna and morphine is a commonly used, 
and is pharmacologically equivalent to belladonna and opium suppositories. 
 
The active suppositories and placebo suppositories will be compounded to be physically 
identical, and will be provided directly to the Principal Investigator located at Wichita 
Women’s Pelvic Surgery Center at Associates in Women’s Health, by the compounding 
pharmacy. The Principal Investigator will not know the identity of the suppositories. The 
data coordinator will maintain a master tracking list of the suppository with an inventory 
or ID number provided by the pharmacy as to which ID numbers are placebos and 
which are the B&O suppositories. The data coordinator will provide the randomization 
scheme to the pharmacy, who will fill each individual prescription based on the order the 
patient is consented into the study (using the participant’s ID number), and will place the 
individual suppository into a blinded pill canister. The Principal Investigator will call the 
data coordinator and the lead pharmacist at the compounding pharmacy when a patient 
has consented and will undergo the procedure. The pharmacist associated with the 
compounding pharmacy will hand deliver the envelope to the clinic, and document the 
pill canister being delivered. The data coordinator will meet the pharmacist at the clinic 
to audit the container, and to confirm the appropriate container is provided to the 
Principal Investigator. The “unblinded” label containing the actual medication provided 
to the patient, including the patient name, date of birth, address, and phone number will 
be concealed in an envelope and carried separately from the pill canister, however, in 
order to comply with DEA guidelines, both will be hand delivered to the clinic. The 
envelope with the identity of the suppository will be in a secure container under lock and 
key, and will only be accessible to the data coordinator. The label will be stored with the 
participant’s study records, and not revealed to the Principal Investigator.  
 
All suppositories will be stored in a locked refrigerator that will be kept in a locked office. 
The temperature will be monitored regularly for quality assurance. The Principal 
Investigator will administer the suppository to the participant prior to the BoNT 
procedure, and will document in the participant’s medical record and study documents 
which pill number was administered to the participant. The data coordinator will monitor 

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and monthly audit logs to ensure randomization assignments are adhered to during the 
course of the study. 
 
A sample from each batch of compounded suppositories will be sent off for third-party 
testing to test the suppositories for chemical validity.  
 
Participant Timeline 
The length of participation in this study will be approximately two weeks from the day of 
the injection procedure. Table 2 illustrates the procedures or tasks to be completed 
during each appointment. 
 
Table 2. ROBIN Trial Participant Timeline 
Appointment 
Task/Objective 
Patient Consents to Undergo Bladder Injection 
Therapy 
 Patient elects to receive BoNT therapy as 
standard of care treatment for overactive 
bladder, neurogenic detrusor overactivity, or 
refractory interstitial cystitis 
 If patient meets inclusion criteria, patient is 
consented and offered enrollment into the study 
 Participant receives a participant ID number 
based on sequential numbering 
 Principal Investigator completes prescription and 
sends to compounding pharmacy to fill based on 
participant ID number 
Day Prior to Procedure 
 If informed consent is obtained, the blinded 
suppository will be hand delivered to the clinic 
by the compounding pharmacy 
 The suppository will be locked in a medicinal 
refrigerator until time of the procedure 
Day of Procedure 
 Participant checks in for procedure, and 
completes pain assessment (Po) 
 Principal Investigator administers the 
suppository or placebo to the participant 
 Participant completes pain assessment after 
receiving analgesia for the procedure (Pa) 
 Participant undergoes BoNT procedure and 
completes pain assessment (P10, P20) 
 Participant completes voiding residual trial 
 Adverse effects or serious events are assessed 
 Participant is released from clinic  
2-weeks follow-up visit 
 Participant completes voiding residual trial and 
adverse effects or serious events are assessed 
 Participant receives $25 gift card incentive for 
completing the study 
 
Risks to Subjects 
Because the patient has already given consent to receive the BoNT therapy, any risks 
associated with the procedure while participating in this study are within normal bounds 
for any patient electing to undergo the procedure. Overall, the risks involving the use of 
the B&O suppository are comparable to not utilizing it during the BoNT therapy 

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procedure. Use of this particular suppository should not significantly increase or 
decrease risks to the patient.  
 
However, investigators believe that there are risks associated with this study. Physical 
risks associated with participating in this study, and related to study procedures include 
drowsiness/nausea associated with the B&O suppository if the participant is randomized 
to the active group. As standard of care after the BoNT procedure, patients are required 
to have a driver, and are advised on to operative a moving vehicle. Participants 
receiving the placebo may experience discomfort with the procedure, which the patient 
is aware of during the consent process for the BoNT therapy.  
 
This research study involves exposure to pain and discomfort, however the risk is 
associated with routine clinical care since there are no established guidelines or 
recommendations for suppository use with analgesia during the BoNT therapy. The risk 
of discomfort and drowsiness/nausea associated with the study is minimal, and if the 
patient were to not participate in the study, would typically receive the B&O suppository 
as part of the Principal Investigator’s routine standard of care. Researchers believe 
there is less than minimal risk associated with psychological, economic, social, and 
legal aspects of this study. 
 
Loss of anonymity is a risk associated with research projects that involve human 
subjects. The research staff working on this study will take every precaution to guard 
patient identity in accordance with HIPPA standards. All study information and data will 
be grouped in aggregate and no individual information will be reported. No patient will 
be identified by name and protections will be in place to keep individual information 
confidential and anonymous.  
 
However, risks are reasonable to the potential benefit from the study. Participation in 
this study will contribute to a better understanding of the treatment of bladder injection 
pain, which outweighs the minimal risk associated with the active group intervention. 
Additionally, this study may also help other patients that need to have the BoNT therapy 
in the future, have a better understanding of treatment options for overactive bladder, 
neurogenic detrusor overactivity, and refractory interstitial cystitis. Furthermore, 
information collected from this study would provide clinicians methods that could 
potentially reduce patient pain during in-office procedures, and would reduce potential 
healthcare costs associated with performing this type of procedure in a hospital facility. 
 
Study Sites 
Study sites for this study include the following locations where the investigators fill 
perform research procedures, or analyze and store data. 
 
Wichita Women’s Pelvic Surgery Center at Associates in Women’s Health (Clinical site) 
3232 E. Murdock St. 
Wichita, KS, 67208 
 
 
 

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University of Kansas School of Medicine – Wichita 
Department of Obstetrics and Gynecology 
551 N. Hillside, Suite 500 
Wichita, KS 67214 
 
Study Personnel 
The study personnel associated with research procedures are listed in Table 3. 
  
Table 3. ROBIN Trial Research Personnel 
Study Personnel 
Affiliation 
Role 
Responsibilities 
Edgar LeClaire, MD KUSM-W 
Department of 
Obstetrics and 
Gynecology 
Clinical 
Instructor 
Principal 
Investigator 
 Determining eligibility 
 Obtaining informed consent 
 Providing on-going 
information to the IRB 
 Completing physical exam 
 Performing clinical 
procedures and intervention 
 Conducting questionnaires 
 Completing study data forms 
 Managing study database 
 Statistical analysis 
 Report generation 
Rachel Wykes, MD, 
PGY-3 
KUSM-W 
Department of 
Obstetrics and 
Gynecology 
Resident 
Resident Co-
Investigator 
 Determining eligibility 
 Obtaining informed consent 
 Conducting questionnaires 
 Completing study data forms 
 Managing study database 
 Statistical analysis 
 Report generation 
 Chart audit 
Jennifer Duong, 
MPH 
KUSM-W 
Department of 
Obstetrics and 
Gynecology 
Staff 
Project and 
Data 
Coordinator, 
Co-
Investigator 
 Determining eligibility 
 Obtaining informed consent 
 Conducting questionnaires 
 Completing study data forms 
 Managing study database 
 Statistical analysis 
 Report generation 
 Chart audit 
 
Recruitment 
Eligible female participants will be recruited from Wichita Women’s Pelvic Surgery 
Center at Associates in Women’s Health, P.A., a urogynecology and gynecologic-
oncology clinic located in south-central Kansas with a collaborative academic 
relationship with University of Kansas School of Medicine-Wichita. 

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Based on the sample size needed to complete this study, investigators will need to 
consent and enroll about 3 patients a month into the study. The Principal Investigator 
believes that with the current number of patients treated with BoNT therapy, the number 
of patients needed to participate is obtainable within 12-18 months. 
 
Screening for Potential Study Participants 
The Principal Investigator will screen potential subjects based on the inclusion and 
exclusion criteria. Potential subjects will have met the clinical criteria to be treated with 
BoNT therapy prior to screening for the study. 
 
Informed Consent Process 
Clinical visits will occur at Wichita Women’s Pelvic Surgery Center at Associates in 
Women’s Health (WWPSC) in Wichita, KS. Investigators and research staff will be 
available to answer patient questions at the time of the informed consent interview. The 
consenting process will take place after patient in-processing according to standard 
clinic operating protocols, and after the patient has satisfied the clinical criteria and has 
elected to undergo BoNT injection therapy with the Principal Investigator.  
 
After electing to undergo the injection therapy, the Principal Investigator will review the 
eligibility criteria to determine if the patient is eligible to participate in the study. If all 
inclusion criteria are met, the Principal Investigator or a member of the research team 
will present the informed consent form to the patient and will discuss the study with the 
potential subject. The patient will be informed that participation is voluntary, and their 
decision to participate will not affect their medical treatment or procedures related to the 
BoNT injection therapy. Consent will only be sought from those patients that meet fulfill 
the study inclusion criteria. All materials will be provided to the patient and the 
conversation will take place in English (Appendix A – ROBIN Consent Form). 
 
After all questions have been answered, and the patient has had adequate time to 
review the informed consent form, if the patient would like to participate, the research 
team will ask the participant to sign the consent form. If the patient would like additional 
time to review the informed consent form and to consider participation, the patient can 
either schedule a visit to complete the form before their visit, or can sign the informed 
consent form when they check in for their procedure. 
 
A copy of the signed consent will be provided to the participant. The Principal 
Investigator will be notified that the patient consents to participate in the study. After 
consenting, the investigators and research assistant will review all materials for 
completeness before the subject leaves the clinic site.  
 
 
If consent to participate in the study is not given, no information collected during the visit 
will be used in the study. Instead, the information will used for normal documentation of 
patient care.  
 

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Patients will be consenting to data collection and to research participation to receive an 
intervention or a placebo above and beyond standard clinical practice. 
 
Alternatives to Participation 
The alternative to participating in this study would be to not participate in the study. The 
patient will still undergo the BoNT therapy as anticipated. Even if the patient declines to 
participate in the study, the patient would still receive the B&O suppository as the 
Principal Investigator’s standard of care, or patients can notify the clinician they do not 
want to utilize a suppository. 
 
Costs to Subjects 
The study subject will be responsible for costs associated with the BoNT injection 
therapy, and standard medical costs associated with their treatment. In the instance that 
the insurance company will not pay for the injection therapy or the associated standard 
of care procedures, the subject will be notified, and the subject will be responsible for 
the costs associated with their medical treatment. If the subject does not have 
insurance, the subject has previously agreed to cover the costs associated with the 
treatment. 
 
The only costs that the subject will not be responsible for are those related to the study 
procedures. The subject is not required to cover the cost of the suppository, or the pain 
assessment forms. 
 
New Study-Related Information 
Although investigators do not anticipate developments in research or information related 
to the study, the study subject will receive new information from investigators via letter 
correspondence. Any correspondence will be disseminated by the Principal Investigator, 
and the data coordinator will track and monitor that each study subject receives the 
information. 
 
Participation Incentive 
Subjects will receive a $25 gift card at the conclusion of the 2-week follow-up 
appointment to assist with travel/driver costs. If the subject withdraws before the 2-week 
follow-up, the participant will not receive an incentive for participation. 
 
Research-Related Injury 
If the study subject were to be injured as a result of study procedures (separate from the 
BoNT therapy), subjects will be advised to immediately contact the Principal 
Investigator, Dr. Edgar LeClaire at (316) 219-6777. Dr. LeClaire will decide what type of 
treatment, if any, is best for the study participant at that time.  
 
 
 

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Data Collection and Protection 
 
Data Collection Procedures 
Data collection will occur after obtaining informed consent for the patient to participate in 
the study. Demographic data will be collected to include clinical, surgical, functional, 
post-procedure, charted data collected as part of routine clinical visit and standard of 
care (Table 4). Data will be collected on a paper form (Appendix B – Data Collection 
Form). Follow-up data will include newly charted clinical and functional data.  
 
Table 4. Summary of Participant Demographic Data Collected 
Date of 1st consultation 
Height 
Weight 
Body Mass Index 
Race/Ethnicity 
Smoking status 
Menopausal status 
Diagnoses 
Prior surgeries 
Past medical history 
Medications 
Indication for BoNT injection procedure 
 
The day of the procedure, the participant will check in at the front desk. A nurse will 
escort the participant back to the procedure room for preparation. The participant will be 
given a pain assessment form with a numeric rating scale that will ask the participant to 
evaluate their bladder pain prior to standard analgesia and the procedure (Appendix C – 
Pain Assessment Form - Po). After completing the assessment, the participant will be 
positioned for the procedure and will be administered standard analgesia plus active or 
placebo suppository (based on randomization assignment). 
 
Aside from suppository placement, BoNT injection protocols that are in compliance with 
best practices established by Allergan® and the FDA will be followed. In summary, 
BoNT will be reconstituted in 10ml normal saline and injected in 1/2ml increments (20 
injections). Standard analgesia consists of bladder instillation with 50-60ml of 1% 
lidocaine solution with 10ml of sodium bicarbonate. Instillation is maintained for 40 
minutes prior to the procedure. During that time, the patient will rotate while on 
procedure table (10 minutes on supine, 10 minutes prone, 10 on each side) to maximize 
bladder wall contact with anesthetic. The patient will then be placed in lithotomy position 
for cystocopic injection of BoNT. A 17 french 30 degree cystoscope will be used. 
Injection will carried out using a flexible botox injection needle designed for the 
procedure. All patients will undergo standard screening for preoperative UTI and 
antibiotic prophylaxis per accepted guidelines. 
 

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After 40 minutes of receiving the analgesic and suppository, and right before the 
procedure, the participant will be asked to report their bladder pain using a numeric 
rating scale (Appendix D – Pain Assessment Form – Pa-P20). 
 
Patients will undergo 20 total injections at time of BoNT treatment. An investigator will 
perform pain assessments during the procedure. During the procedure, the participant 
will be asked their bladder pain using the numeric rating scale after the first 10 of 20 
injections performed during the procedure and after the next 10 of 20 performed during 
the procedure (Appendix D – Pain Assessment Form – Pa-P20).  
 
After the procedure is completed, the participant will be asked to complete a voiding 
trial, and will be given a pain assessment form, answering a Likert scale question 
regarding their satisfaction with their pain management during the procedure (Appendix 
E – Pain Assessment Form - Post BoNT). After the voiding trial is completed and the 
Principal Investigator has provided standard medical counseling and care after the 
procedure, the participant is released from the clinic.  
 
Patient pain outcomes will be measured using numeric rating scales (NRS) and 
satisfaction with pain management during the procedure. The Principal Investigator will 
perform the clinical evaluation and in-office procedures associated with this study. The 
investigators will assist with the pain assessments. Patient information will be collected 
as part of the normal course of care associated with routine post-surgical visit and will 
be charted according to routine clinical practice. Pain assessments will be collected for 
research purposes. 
 
Description of Follow-Up 
During the informed consent process, subjects will agree to a standard of care follow-up 
with the Principal Investigator, two weeks after their in-office procedure where they will 
undergo PVR assessment. The Principal Investigator will perform a clinical exam as 
part of their standard of care. Adverse and serious effects will be assessed during 
follow-up. Both the results of the PVR assessment, adverse and serious effects, and 
result of urine culture will be documented (Appendix F – Assessment Form – 2-Week 
Follow-up). 
 
Cessation Rules/Termination of Study 
During the consenting process, subjects will be advised that they may voluntarily 
withdraw from this study at any time. They will not be obligated to reveal their reason for 
withdrawal. Additional circumstances for which a subject may not continue study 
participation include death, or lost to follow-up status. A subject will also be withdrawn 
from the study if their procedure was not performed at Associates in Women’s Health. 
Moreover, a subject will be withdrawn from the study if the subject does not follow the 
study requirements. The Principal Investigator has discretion in removing a patient from 
the study if study requirements are not met. 
 
Subjects terminated from the study will undergo standard treatment of care. All data 
collected during the study prior to cessation will be kept on hold at the discretion of the 

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investigator(s) and research assistant, unless the subject cancels the permission for 
researchers to use the collected data. 
 
To withdrawal from the study, the subject will need to write a statement to the Principal 
Investigator. The mailing address to withdraw is: Edgar LeClaire, MD, KU School of 
Medicine- Wichita, Department of Obstetrics and Gynecology, 551 N. Hillside, Suite 
500, Wichita, KS 67214.  
 
Once a written statement has been received, the researchers will remove the subject 
from the current list of subjects and will be placed on the withdrawn list. Information that 
had already been collected from the patient will be kept. Subjects will continue to 
receive standard treatment of care; however, all data collected after receiving the study 
withdrawal statement will not be added to the cumulative study data. 
  
Human Subjects Protections 
Researchers involved with this study will have Human Subjects and HIPAA Certification. 
This proposal will be submitted to two IRBs; the Wichita Medical Research and 
Education Foundation IRB and the University of Kansas School of Medicine – Wichita 
Human Subjects Committee 2 IRB. This study will not commence until final approval is 
received from the IRBs. 
 
Methods to Minimize Risks 
To minimize the risks associated with this study, the privacy of potential subjects will be 
maintained as all Protected Health Information (PHI) will be protected and have limited 
access. Subject names and clinic record numbers will be maintained on a master list 
linked to a unique, assigned identification code generated independent of the medical 
record number. Much of the information we are seeking to collect is routinely collected 
and placed in the patient clinic and surgery charts. Access to PHI is necessary to 
connect patient surveys and assessments to information collected from the electronic 
medical record.  
 
The master list will be maintained under secure conditions at all times. The master list 
will be stored at the University of Kansas School of Medicine - Wichita, Department of 
Obstetrics and Gynecology (551 N. Hillside, Suite 500, Wichita, KS 67214, in a private 
room under lock and key. Electronic copies of the master list will be password-protected 
and stored on encrypted computers/laptops. Only the data coordinator will have access 
to the master list in the department. The master list will be destroyed once all data has 
been deemed complete and analyzed, and it is determined that the master list is no 
longer necessary. 
 
Only the listed investigators and their designated staff will have access to the master list 
and study data. The Institutional Review Boards, US Department of Health and Human 
Service, the Office of Human Research Protections, and other government and 
regulatory bodies, as required by law, may have access to this research data. 
 

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Research assistants enlisted to assist with this study will be closely supervised by the 
Principal Investigator. Those involved in direct patient care responsibilities, and 
assisting clinicians are located at Associates in Women’s Health, and will not perform 
activities beyond their scope of care or expertise. Information technology protections 
and firewalls that are in place at this facility will protect the electronic data stored.  
 
 
Data Security 
Paper forms will be maintained under secure conditions at all times. The paper forms 
used in this study will not have participant protected health information listed, and will be 
kept in a locked office at all times. Data forms will be kept confidential during the 
conduct of this study. Research materials, such as protocols, IRB documents, 
participant information and data forms (after completion of data collection and analysis) 
will be kept in locked file cabinets in the University of Kansas School of Medicine – 
Wichita, Department of Obstetrics and Gynecology at Wesley Medical Center, 551 N. 
Hillside, Suite 500, Wichita, Kansas 67214. 
 
Documents and study related materials will be maintained under lock and key. 
Electronic files will be password-protected and encrypted, and will only be accessed by 
researchers listed on this study. Portable data devices (flash drives) will be encrypted 
and password-protected and will be maintained in secure locations in locked offices 
(either a co-investigator’s office or the research assistant’s office). At the conclusion of 
the study, all study related materials will be kept in locked file cabinets. Electronic files 
will have multiple firewalls and passwords to help keep information confidential. 
Electronic databases will be kept based on the record retention guidelines previously 
stated, and will be stored on password-protected and encrypted hard drives. 
 
Information collected from paper forms will be entered into a computerized data file, and 
the file will be password protected and encrypted. Passwords will be subject to 
scheduled changes.  The master list will be kept separately from the data collection 
forms. Access to study databases is restricted to an as needed basis to identified 
investigators and will be protected by appropriate firewalls. The database will be 
password-protected and encrypted. Files sent by email will first be password-protected 
and the email will be encrypted and sent via secure email. 
 
Study Monitoring 
The research staff will provide oversight, supervision, and monitoring of the data 
collection and will insure the integrity of the data which will ultimately ensure subject 
confidentiality. The study sites will be either the Principal Investigator’s local clinic 
practice site, or those affiliated with the study personnel at the University of Kansas 
School of Medicine – Wichita. 
 
Secure and Maintain IRB Approval at All Sites: 
The Wichita Medical Research and Education Foundation IRB, in conjunction with the 
University of Kansas School of Medicine – Wichita Human Subjects Committee 2 IRB, 
will serve as the IRBs of record for this study, to include all the study locations listed 
previously. All protocol deviations, amendments, revisions, and continuing review 

ROBIN Trial 
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reports will be promptly compiled by the project coordinator, reviewed by the principal 
investigator and co-investigators, and provided to the IRBs. All research within the 
scope of this project will be conducted under IRB policies and guidelines. 
 
Obtain IRB Approvals Prior to Implementing Changes to Protocol: 
Investigators wish to assure the IRBs that any amendments to the protocol or 
supporting documents will be submitted for approval prior to implementation; problems 
associated with the research will be reported in accordance with IRBs policies. 
 
Ensure general coordination of study conduct: 
The principal investigator agrees to accept responsibility for the scientific conduct of this 
study and for the rights and welfare of human subjects.  General oversight of the 
coordination of this study will be provided by the principal investigator, sub-
investigators, and project coordinator. 
 
Modifications to Study Protocol and Oversight: 
Each review will consider whether or not the study should continue without change, be 
modified, or be terminated.  Recommendations regarding modification of the design and 
conduct of the study might include: 
1. Modification of the study protocol based upon review of the safety data;  
2. Optional approaches when the incidence of primary study outcomes is 
substantially less than expected such as recommendations to extend study site;  
and 
3. Corrective actions regarding the study site. 
Any modifications to the study protocol will be submitted to the IRBs for approval prior to 
implementation of the changes. 
 
To monitor adverse events or other unanticipated problems: 
In lieu of a DSMB, investigators will serve in this capacity, in which they will be 
responsible for the following: 
1. Interim/cumulative data for evidence of study-related adverse events; 
2. Interim/cumulative data for evidence of efficacy when appropriate; 
3. Performance of the study site; 
4. Adequacy of compliance with goals for subject selection; and 
5. Factors external to the study such as scientific or therapeutic developments that 
may impact participant safety or the ethics of the study. 
 
The Principal Investigator and project coordinator will assume responsibility for: 
1. Data quality, completeness, and timeliness; 
2. Completeness of survey instruments; 
3. Adherence to the protocol; and  
4. Factors that might affect the study outcome or compromise the confidentiality of 
the trial data (such as protocol deviations). 
 
Moreover, assessments for participant safety, study conduct and progress, and efficacy 
will be done. Periodic reviews of the same factors will be carried out. Each review will 

ROBIN Trial 
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consider whether or not the study should continue without change, be modified, or be 
terminated. Steps to unmask participants will be used to ensure participant safety if 
needed. 
 
Investigator’s Ethical and Regulatory Responsibilities: 
Protocol adherence is the primary responsibility of the Principal Investigator. The co-
investigators, and project coordinator will serve to support protocol adherence efforts 
and maintain an understanding of all protocol details. The principal investigator will 
consult with the other investigators regarding protocol revisions and amendments 
before adopting such changes. The IRBs will be notified of any problems during the 
conduct of this study. 
 
Adverse Event Assessment and Reporting 
The study team will be reviewing and assessing subject safety and data on a monthly 
basis. Participant pain assessments and clinical outcomes will be regularly reviewed to 
monitor patient safety. The Clavien-Dindo classification system will be used to monitor 
for adverse events and complications [33]. Adverse events specifically related to BoNT 
injection will also be monitored to include urinary tract infection and gastroparesis [31].  
 
In the case an adverse event were to occur, the study investigator(s) will assume 
responsibility for reporting and documenting any complications. All serious events and 
adverse effects will be recorded on the participant’s case record forms. In addition, all 
serious adverse and unanticipated adverse effects will be reported to the Institutional 
Review Boards by telephone, or in writing, within five (5) business days after the 
investigators first learn of the event by either the investigator(s) or the project 
coordinator.  
 
The investigators are required to document all general medical complications, including, 
but not limited to the following: date of occurrence, date diagnosed, type of 
complication, and treatment. The investigator(s) and research assistant are responsible 
for complying with any reporting requirement of the reviewing IRBs. 
 
Adverse events will be assessed after the suppository has been used, during the 
procedure, and during the voiding trial. During the two week follow-up visit, adverse 
events will also be assessed. The investigators do not believe there will be a need to 
stop or alter the study, but will stop the study if requested by the Institutional Review 
Board. 
 
Record Retention 
All study related documents (research materials such as protocols, IRB documents, 
participant information and data forms after completion of data collection and analysis) 
will be retained for fifteen (15) years from the data of initial IRB approval, and will be 
kept in locked cabinets located at the University of Kansas School of Medicine – Wichita 
Department of Obstetrics and Gynecology, 551 N. Hillside, Suite 500, Wichita, Kansas 
67214 under lock and key at the conclusion of this study. At the time of document 

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disposal, documents will be shredded according to KUMC Research Institute Record 
Retention guidelines. 
 
Dissemination of Results 
Once the research is completed, it will be submitted to gynecologic journals and 
conferences, particularly those specializing in urogynecology.  
 
Project Timeline 
The project seeks to obtain Institutional Review Board approval from the IRBs by 
September 2015 (Table 5). This research project is anticipated to be completed by April 
2017. The investigators anticipate conducting preliminary analysis after one year, and 
will complete continuing review forms as needed to complete the study. 
 
Table 5. ROBIN Trial Project Timeline 
 
PROJECT LAUNCH 
Project Deliverables (X) 
Academic Year 2015 - 2016 
7 
8 
9 
10 
11 
12 
1 
2 
3 
4 
5 
6 
7 
J 
A 
S 
O 
N 
D 
J 
F 
M 
A 
M 
J 
J 
  
  
  
  
  
  
  
  
  
  
  
  
 
Assemble project staff, create study protocol, 
submit for IRB approval and study funding 
  
  
  
  
  
  
  
  
  
  
  
  
 
Submit project for IRB approval and funding 
 
 
 
 
 
 
 
 
 
 
 
 
 
Receive IRB Approval 
  
 X 
  
  
  
  
  
  
  
  
  
 
Train study team and support staff 
  
  
  
  
  
  
  
  
  
  
  
  
 
Recruit patients from local providers offices 
  
  
  
  
  
  
  
  
  
  
  
 
Enroll patients and collect data 
 
 
 
 
 
 
 
 
 
 
 
 
 
Team meetings to discuss research plan, data 
quality, and progress on objectives 
 
 
 
 
 
 
 
 
 
 
 
 
 
Conduct preliminary analysis  
  
  
  
  
  
  
  
  
  
  
  
  
 
Review findings with team 
  
  
  
  
  
  
  
  
  
 
  
  
 
IRB Continuing Review 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Academic Year 2016 - 2017 
Finalize data analysis and conclusions 
 
 
 
 
 
 
 
 
 
 
 
 
 
Draft abstract and submit to regional/national 
conferences 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Disseminate preliminary findings at 
regional/national conferences 
 
 
 
X 
 
 
 
 
 
X 
  
 
 
Draft manuscript 
 
 
 
 
 
 
 
 
 
 
  
 
 
Submit manuscript for publication 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 

ROBIN Trial 
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Budget and Justification 
Investigators will be requesting funding to cover costs related to the study and 
registration for the Principal Investigator and the Resident Investigator to present the 
findings of this study at the 2016 American Urogynecologic Society Annual Meeting. A 
detailed budget is provided below. 
 
Personnel Costs: 
$0.00 
LeClaire, Edgar, MD, Principal Investigator (PI), will be responsible for managing and 
providing direction on all aspects of the project, ensuring that the budget and timetable 
targets are met, and providing direction to the other research personnel. Specifically he 
will facilitate communication between members of study team, and oversee conduct of 
the study, ensure all requirements for the Institutional Review Board are met, and 
contribute to reports, and dissemination. Dr. LeClaire will be performing the clinical 
procedures associated with this study, perform the data analysis and create reports, 
and disseminate results at national meetings. 
 
Rachel Wykes, MD, PGY-3, Co-investigator, will be responsible for managing and 
providing direction on all aspects of the project, ensuring that the budget and timetable 
targets are met, support Institutional Review Board approval/revisions, and providing 
direction to the other research personnel. Specifically she will facilitate communication 
between members of study team, and oversee conduct of the study personnel, perform 
study procedures, assist with data analysis, and create reports, and dissemination at 
national meetings. 
 
Jennifer Duong, MPH Study Personnel, will be responsible for facilitating team 
communication, coordinating protocol implementation logistics at the study site, and 
drafting/submitting Institutional Review Board reports and summaries, support 
Institutional Review Board approval/revisions, assist with team coordination, assist with 
data cleaning, assist with data analysis, review reports and submit abstracts for 
conference presentations.   
 
Fringe Benefits:  
$0.00 
None requested. 
 
Equipment:  
$0.00 
None requested. 
 
Supplies:  
$1825.00 
Based on the quote provided by the compounding pharmacy, compounded belladonna 
and morphine pills will cost $15.00 per pill the placebo pills will cost $10.00. Thus, 20 
compounded belladonna and morphine pills will cost $300.00 and 20 placebo pills will 
cost $200.00. Extra suppositories will be created to send for third-party validity testing 
and in the case where a suppository is deemed defective or dropped. Third-party 
validity testing will cost approximately $500.00 Participants will receive a $25 Walmart 
gift card from Walmart for participating. The total cost for incentives for 26 participants 
will be $650.00. Paper supplies for surveys and printing will cost $100.00. The poster 

ROBIN Trial 
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25 
 
will be a 4x3 poster board used during presentations, which will cost $75.00. Total costs 
for supplies will be $1825.00. 
 
Other Expenses: 
$900.00 
Registration to the 2016 American Urogynecologic Society Annual Meeting will be 
approximately $450.00 for each attendee. The Principal Investigator and the resident 
co-investigator will attend to present the findings from this study. The total cost of 
registration to the meeting will be $900.00. 
 
Subcontractor Costs:  
$0.00 
None requested.  
 
Personnel Costs 
$0.00 
Fringe Benefits  
$0.00 
Equipment 
$0.00 
Supplies 
$1825.00 
Other Expenses 
$900.00 
Subcontractor Costs  
$0.00 
Total Projected Study Costs:  
$2725.00 
 
 

ROBIN Trial 
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Appendices 
Appendix A – ROBIN Consent Form 
Appendix B – Data Collection Form 
Appendix C – Pain Assessment Form – Po 
Appendix D – Pain Assessment Form – Pa-P20 
Appendix E – Pain Assessment Form – Post BoNT 
Appendix F – Assessment Form – 2-Week Follow-up 
 

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References 
 
1. 
Coyne, K.S., et al., The impact of urinary urgency and frequency on health-
related quality of life in overactive bladder: results from a national community 
survey. Value in Health, 2004. 7(4): p. 455-63. 
2. 
Hu, T.W., et al., Costs of urinary incontinence and overactive bladder in the 
United States: a comparative study. Urology, 2004. 63(3): p. 461-5. 
3. 
Wu, J.M., et al., Forecasting the prevalence of pelvic floor disorders in U.S. 
Women: 2010 to 2050. Obstetrics & Gynecology, 2009. 114(6): p. 1278-83. 
4. 
Tyagi, S., et al., The overactive bladder: Epidemiology and morbidity. Urol Clin 
North Am, 2006. 33(4): p. 433-8, vii. 
5. 
Hanno, P.M., et al., AUA guideline for the diagnosis and treatment of interstitial 
cystitis/bladder pain syndrome. J Urol, 2011. 185(6): p. 2162-70. 
6. 
Hanno, P.M., et al., Diagnosis and treatment of interstitial cystitis/bladder pain 
syndrome: AUA guideline amendment. J Urol, 2015. 193(5): p. 1545-53. 
7. 
Chung, E., Botulinum toxin in urology: a review of clinical potential in the 
treatment of urologic and sexual conditions. Expert Opin Biol Ther, 2015. 15(1): 
p. 95-102. 
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