Conditions: Interstitial Cystitis Bladder Pain Syndrome
Keywords: Interstitial cystitis Bladder pain syndrome IC/BPS Women Pelvic pain Urologic pain Bladder instillation Kenalog Steroid
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 90
Healthy volunteers: no

Brief summary:
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a condition that results in long-term bladder and pelvic pain. IC/BPS affects women more often than men. How the disorder develops is not completely known. Bladder instillation is a commonly used treatment in which a mixture of different ingredients are passed into the bladder to help IC/BPS symptoms. There is room to learn more about bladder instillations and which ingredients in them work best. The purpose of this study is to compare the effectiveness of a bladder instillation that contains a steroid (triamcinolone acetonide) to a bladder instillation that does not contain a steroid to treat IC/BPS in women. The study hypothesis is that women with IC/BPS treated with bladder instillations that contain a steroid will have improved outcomes compared to women treated with bladder instillations that do not contain a steroid.

Detailed description:
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder involving the genitourinary tract. IC/BPS disproportionately affects women with over 80% of patients with IC/BPS as female. Like other chronic pain conditions, IC/BPS is physically and emotionally taxing on patients. IC/BPS costs the United States over $100 million annually due to direct healthcare costs and loss of worker productivity. The exact pathophysiology of the disease is unknown, leading to a limitation in our ability to treat the disorder effectively. The current leading etiologic theory is that IC/BPS is a neurologically-derived chronic systemic pain syndrome due to its association with musculoskeletal pelvic pain, irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia, and vulvodynia. Although several options exist to treat IC/BPS, therapeutic effects are often transient. Previous studies in chronic pain disorders have shown that multimodal treatment is more effective than single-agent treatment, so future therapy should aim to augment rather than replace current treatments. Bladder instillation is a commonly used treatment in which a mixture of different agents is instilled into the bladder to improve IC/BPS symptoms. The data on the efficacy of bladder instillations, as well as which ingredients in the mixture are effective, are limited. Small studies have shown the potential of steroids in decreasing IC/BPS; the mechanism of action is hypothesized to be due to decrease inflammation in the bladders of these patients. The knowledge gap that exists is the necessity of a steroid in the bladder instillation treatment for IC/BPS symptoms especially since this tends to be the most expensive ingredient.

To evaluate the utility of a steroid in the bladder instillation treatment of IC/BPS, we propose a randomized, double-blind, controlled trial that will compare the efficacy of bladder instillations with and without triamcinolone acetonide on IC/BPS symptoms in women. We hypothesize that the addition of triamcinolone acetonide in bladder instillation therapy will result in a more robust treatment response than bladder instillations without triamcinolone acetonide. Our rationale is based on 1) the results of small studies that showed improvement of IC/BPS symptoms with use of a steroid and 2) the hypothesized mechanism of action of steroids decreasing inflammation in the bladder.

Arms:
arm 1: Six weekly bladder instillations of standard cocktail plus triamcinolone acetonide. Standard cocktail= heparin (10,000 units), 2% viscous lidocaine (10 mL), 8.4% sodium bicarbonate (15 mL of 1 mEq/mL), and 0.5% bupivacaine (10 mL of 5 mg/mL) plus triamcinolone acetonide (1 vial, 40 milligrams (mg)/1 milliliters (mL). arm 2: Six weekly bladder instillations of standard cocktail without triamcinolone acetonide. Standard cocktail= heparin (10,000 units), 2% viscous lidocaine (10 mL), 8.4% sodium bicarbonate (15 mL of 1 mEq/mL), and 0.5% bupivacaine (10 mL of 5 mg/mL).

Interventions: intervention 1: Bladder instillation WITH triamcinolone acetonide intervention 2: Bladder instillation WITHOUT triamcinolone acetonide
Intervention descriptions: intervention 1: Bladder instillation mixture of heparin (10,000 units), 2% viscous lidocaine (10 mL), 8.4% sodium bicarbonate (15 mL of 1 mEq/mL), 0.5% bupivacaine (10 mL of 5 mg/mL) plus triamcinolone acetonide (1 vial, 40 milligrams (mg)/1 milliliters (mL). intervention 2: Bladder instillation mixture of heparin (10,000 units), 2% viscous lidocaine (10 mL), 8.4% sodium bicarbonate (15 mL of 1 mEq/mL), and 0.5% bupivacaine (10 mL of 5 mg/mL).

Protocol document:
Prot_SAP_000.pdf: 
Study Title:  Randomized controlled trial comparing two different bladder instillation treatments for interstitial 
cystitis/bladder pain syndrome.  
Protocol version:  January 23, 2019
Page 1 of 18
Administrative information
Project Title:  Randomized controlled trial comparing two different bladder instillation 
treatments for interstitial cystitis/bladder pain syndrome. (January 23, 2019)
Trial registration:  ClinicalTrials.gov – NCT03463915
Protocol version:  18.0209
Funding:  None
Roles and responsibilities:  
Principal Investigator: 
Dr. Kate Meriwether (Assistant Professor)
                                        
Department of Obstetrics, Gynecology & Women’s Health
   
Division of Female Pelvic Medicine and Reconstructive    
            Surgery
                                        
550 South Jackson Street
                                        
Louisville, KY  40202             
Co-Investigators:
Dr. Olivia Cardenas-Trowers (Fellow)
Dr. Sean Francis (Associate Professor)
Dr. James Ryan Stewart (Fellow) 
Dr. Ankita Gupta (Fellow)
                            
Department of Obstetrics, Gynecology & Women’s Health
Division of Female Pelvic Medicine and Reconstructive 
Surgery 
                             
550 South Jackson Street
Louisville, KY  40202 
Study Sites: Springs Reproductive Endocrinology and Female Pelvic Medicine Clinic       
                   
University Health Care Outpatient Center (HCOC) 
Sub-investigators: 
None
Regulatory Coordinator: 
Heather Lange, APRN
                                               University of Louisville, Division of FPMRS
Springs Clinic, 6420 Dutchman’s Parkway, Suite 190
Research Protocol
 
Protocol Date:  January 23, 2019


Study Title:  Randomized controlled trial comparing two different bladder instillation treatments for interstitial 
cystitis/bladder pain syndrome.  
Protocol version:  January 23, 2019
Page 2 of 18
Introduction
Protocol Summary/Purpose: 
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder involving 
the genitourinary tract.  IC/BPS disproportionately affects women with over 80% of 
patients with IC/BPS as female.[1]  Like other chronic pain conditions, IC/BPS is 
physically and emotionally taxing on patients.  IC/BPS costs the United States over $100 
million annually due to direct healthcare costs and loss of worker productivity.[2]  The 
exact pathophysiology of the disease is unknown, leading to a limitation in our ability to 
treat the disorder effectively.  The current leading etiologic theory is that IC/BPS is a 
neurologically-derived chronic systemic pain syndrome due to its association with 
musculoskeletal pelvic pain, irritable bowel syndrome, chronic fatigue syndrome, 
fibromyalgia, and vulvodynia.[3-6]  Although several options exist to treat IC/BPS, 
therapeutic effects are often transient.[7,8]  Previous studies in chronic pain disorders 
have shown that multimodal treatment is more effective than single-agent 
treatment,[9,10] so future therapy should aim to augment rather than replace current 
treatments.  Bladder instillation is a commonly used treatment in which a mixture of 
different agents are instilled into the bladder to improve IC/BPS symptoms.  The data on 
the efficacy of bladder instillations as well as which ingredients in the mixture are 
effective is limited.[11,12]  Small studies have shown the potential of steroids in 
decreasing IC/BPS; the mechanism of action is hypothesized to be due to decrease 
inflammation in the bladders of these patients.[13,14] The knowledge gap that exists is 
the necessity of a steroid in the bladder instillation treatment for IC/BPS symptoms 
especially since this tends to be the most expensive ingredient. 
To evaluate the utility of a steroid in the bladder instillation treatment of IC/BPS, we 
propose a randomized, double blind, controlled trial that will compare the efficacy of 
bladder instillations with and without triamcinolone acetonide (Kenalog) on IC/BPS 
symptoms in women.  We hypothesize that the addition of Kenalog in bladder instillation 
therapy will result in a more robust treatment response than bladder instillations without 
Kenalog.  Our rationale is based on 1) the results of small studies that showed 
improvement of IC/BPS symptoms with use of a steroid and 2) the hypothesized 
mechanism of action of steroids decreasing inflammation in the bladder.  
Objectives: 
Primary objective:  
1. To determine if IC/BPS patients will have a greater treatment response to 
bladder instillations with Kenalog plus oral than to bladder instillations without 
Kenalog.  
Secondary objectives:
1. Cost-analysis of bladder instillations with versus without Kenalog.
2. Evaluate how a history of previous IC/BPS treatment or lack thereof correlates 
with treatment response.


Study Title:  Randomized controlled trial comparing two different bladder instillation treatments for interstitial 
cystitis/bladder pain syndrome.  
Protocol version:  January 23, 2019
Page 3 of 18
3. Examine how patient-reported diagnoses of certain conditions (e.g., irritable 
bowel syndrome, fibromyalgia, chronic pain, chronic pelvic pain, vulvodynia, 
anxiety, depression, chronic fatigue syndrome) correlate with treatment 
response.
4. Determine treatment response of subgroups of patients with and without 
prominent overactive bladder (OAB) symptoms. 
Hypothesis:
We hypothesize that patients with IC/BPS will have greater improvement in their general 
symptoms when treated with bladder instillations with Kenalog than IC/BPS patients 
treated with bladder instillations without Kenalog.
Introduction and Background:
IC/BPS is not isolated to the genitourinary tract, but is likely a systemic disorder, based 
on IC/BPS patients’ tendency to have other concurrent pain and inflammatory organ 
disorders.[3-6]  The association of IC/BPS with other systemic, inflammatory syndromes 
is so strong that, in 2008, the National Institutes of Health initiated the Multidisciplinary 
Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network to 
scientifically explore the connections between urological chronic pelvic pain and other 
physiological systems.[15]  
Given the encouraging evidence, it is imperative to study the applicability of anti-
inflammatory agents, such as steroids, in the treatment of IC/BPS symptoms.  The 
expected outcome of this clinical trial is that Kenalog will be an efficacious agent in 
bladder instillations in treating IC/BPS symptoms in women.  The significance of this 
outcome is that steroids as a drug class will be further supported as an important additive 
therapeutic agent in the treatment of IC/BPS, as they have already shown to be in other 
inflammatory disorders throughout the body.  The pay-off of this study is not only 
decreasing the burden of IC/BPS, which costs the United States over $70 billion a year, 
but also paving the way for future studies to evaluate steroids as an adjuvant therapy in 
IC/BPS.
Small studies (<40 patients) have shown improvement of IC/BPS symptoms in patients 
with use of steroids.  However, no previously published studies have evaluated the 
efficacy of Kenalog in bladder instillations using this larger size study design.  The 
proposed research is innovative: (1) it builds upon the current evidence that IC/BPS is a 
systemic chronic pain condition that may respond to steroid medications and (2) it is a 
bigger and more rigorous study than previously published studies evaluating the role of 
steroids in bladder instillation treatment of IC/BPS in women.  Based on the results of 
this study, new and improved therapeutic options will be attainable for IC/BPS and other 
pelvic floor disorders.
Trial design:
This will be a single center, randomized, double-blind, controlled trial.  Women will be 
recruited from a subspecialty clinic at the University of Louisville and be eligible for 
participation if they have selected a course of bladder instillation treatments with their 


Study Title:  Randomized controlled trial comparing two different bladder instillation treatments for interstitial 
cystitis/bladder pain syndrome.  
Protocol version:  January 23, 2019
Page 4 of 18
physician as therapy for a diagnosis of IC/BPS.  Eligible consenting participants will 
undergo randomization with equal probability of assignment to one of the two groups: (1) 
bladder instillation with Kenalog (2) bladder instillation without Kenalog.  They will 
undergo weekly bladder instillations for 6 weeks.  Patients and providers will be blinded 
to study allocation.  Clinical outcomes will be assessed at 3 weeks into treatment (3 
weeks into bladder instillations) and at the end of treatment (6 weeks).
Methods and Procedures:  Participants, interventions, and outcomes
Study setting:
Subjects will be recruited from the ULP Female Pelvic Medicine and Reconstructive 
Surgery (FPMRS) practice at the University of Louisville Health Care Outpatient Center 
(HCOC) and the Springs Medical Center.  
 
Study Sites: 
o
University Health Care Outpatient Center (HCOC)    
o
Springs Medical Center 
Eligibility criteria:
Eligible women will be offered participation in the trial by clinic providers and will sign 
an informed consent with the study investigators prior to completing further study materials 
or receiving any interventions for IC/BPS.  
Inclusion Criteria: 

Age   18-years old

Women with IC/BPS who have a score of ≥ 6 on either index (problem or symptom 
index) of the O’Leary-Sant questionnaire who have selected bladder instillations as 
part of their IC/BPS treatment

Suitability for follow-up
Exclusion Criteria: 

Contraindications to the ingredients used in the bladder instillations
o
In particular: allergy to ingredients
o
Diagnosis of idiopathic thrombocytopenic purpura

Does not desire to undergo bladder instillation therapy or unwilling to undergo 
bladder instillation therapy on schedule mandated by study

Have a known alternative diagnosis explaining bladder pain symptoms that would 
preclude the diagnosis of IC/BPS (e.g. radiation cystitis, active urinary tract 
infection with bacteria or fungus treated within last 2 weeks or diagnosed at index 
visit, bladder injury or trauma within the last 30 days) 

Inability to speak or read English

Bladder instillation within the past 4 weeks


Study Title:  Randomized controlled trial comparing two different bladder instillation treatments for interstitial 
cystitis/bladder pain syndrome.  
Protocol version:  January 23, 2019
Page 5 of 18
Interventions:
Eligible patients will be randomized by a research statistician to one of two possible 
interventions:
1. Bladder instillation with Kenalog
2. Bladder instillation without Kenalog
The randomization sequence, generated by a statistician that is uninvolved in patient 
recruitment, will be in randomly alternating block sizes of 6-10 with a 1:1 distribution in 
each block.  The sequence will be attached by a research medical assistant, also 
uninvolved in patient selection and recruitment, to the numbering of otherwise unmarked, 
identical syringes containing either a bladder instillation mixture with Kenalog or a 
mixture without Kenalog.  The appearance of the syringes will be identical in every way 
except for the patient number on the labelling.  The study investigators recruiting, 
treating, or assessing the patient during the study will not be aware of the patient’s 
randomization, and the randomization sequence will not be opened until the last patient is 
through with the study unless an adverse event mandates.
All study bladder instillation mixture will be drawn up in syringes, randomized, and 
dispensed (given to provider) by one of the medical assistants.  The providers will be 
blinded to the study mixture and will perform the bladder instillations.  The bladder 
instillation ingredients will be prepared in a standardized fashion by a trained medical 
assistant.  The patients will undergo bladder instillations using a standardized technique 
by a physician or nurse practitioner.  The medical practitioner will swab the external 
urethral meatus with betadine (or other appropriate cleansing agent if patient has an 
iodine allergy) and then instill approximately 5 mL of 1% viscous lidocaine in the 
urethra, letting the viscous lidocaine sit for 1 to 10 minutes.  A pediatric (8 French) 
straight-tip catheter will be inserted to drain the bladder and collect a urine specimen for 
culture if indicated.  After the bladder is drained, the bladder will be instilled with either a 
mixture of triamcinolone acetonide (1 vial, 40 milligrams (mg)/1 milliliters (mL)), 
heparin (10,000 units), 2% viscous lidocaine (10 mL), 8.4% sodium bicarbonate (15 mL 
of 1 mEq/mL), and 0.5% bupivacaine (10 mL of 5 mg/mL).  After the instillation, the 
women will lay supine or move from supine to lateral positions intermittently for 20-30 
minutes.  They will then urinate the instillation.  If a patient has previously demonstrated 
the ability to urinate without difficulty following an instillation, she may depart the office 
after 20-30 min and urinate the instillation in a more private, non-office setting.  
If patients have a reaction to the bladder instillation or desire to stop the instillations, they 
may do so.  Participants will be permitted to obtain any relevant concomitant care and 
interventions during the trial.   
Outcomes
All outcome measures will be collected at 3 weeks into the bladder instillation schedule  
and again at the completion of the bladder instillations (6 weeks into study participation).


Study Title:  Randomized controlled trial comparing two different bladder instillation treatments for interstitial 
cystitis/bladder pain syndrome.  
Protocol version:  January 23, 2019
Page 6 of 18
Primary Outcome:  
1. Treatment response as measured by the score of the O’Leary-Sant questionnaire 
[16,17] as compared between study groups at completion of the bladder 
instillations.  
Secondary Outcomes:  
1. O’Leary-Sant subscores (problem and symptom index) at the completion of 
treatment 
2. Change in O’Leary-Sant total scores and subscores (problem and symptom 
indices scores) from baseline to last collected measure
3. Pelvic pain and urgency/frequency (PUF) questionnaire [18]
4. Overactive Bladder Questionnaire (OABq) [19]
5. Pelvic floor distress inventory (PFDI ) [20]
6. Sexual function measured by the Pelvic Organ Prolapse Incontinence Sexual 
Questionnaire, IUGA-Revised (PISQ-IR) questionnaire [21-23]
7. Visual Analogue Scale (VAS) for pain as measured on marking on 10-
centimeter (cm) ruler (measured in cm, 0= no pain and 10= most severe pain 
possible) 
8. Prevalence and nature of adverse events related to study medications
9. The prevalence of notable OAB symptoms in the study population and in the 
different study groups, as defined by OABq score ≥ 8
10. The prevalence of concurrent pain or irritative organ disorders (irritable bowel 
syndrome, fibromyalgia, chronic pain, chronic pelvic pain, vulvodynia, 
anxiety, depression, chronic fatigue syndrome) in the study population and in 
the different study groups
11. Perform cost-analysis of two treatment groups
Participant timeline:
Upon recruitment, women will complete questionnaires (Figure 1) about their 
characteristics and health history, presence or absence and number of other pain 
syndromes related to IC/BPS (irritable bowel syndrome, fibromyalgia, chronic pain, 
chronic pelvic pain, vulvodynia, anxiety, depression, chronic fatigue syndrome), and 
complete the following reliable, validated questionnaires as follows:
(1) O’Leary-Sant questionnaire (problem and symptom index scores) [16,17]
(2) Pelvic pain and urgency/frequency (PUF) questionnaire [18]
(3) Overactive Bladder Questionnaire (OABq) [19]
(4) Pelvic floor distress inventory (PFDI) [20]
(5) Sexual function measured by the Pelvic Organ Prolapse Incontinence Sexual 
Questionnaire, IUGA-Revised (PISQ-IR) questionnaire [21-23]
(6) Visual Analogue Scale (VAS) for pain as measured on marking on 10-
centimeter (cm) ruler (measured in cm, 0= no pain and 10= most severe pain 
possible) 


Study Title:  Randomized controlled trial comparing two different bladder instillation treatments for interstitial 
cystitis/bladder pain syndrome.  
Protocol version:  January 23, 2019
Page 7 of 18
Bladder instillation will be performed weekly with the same mixture that the patient was 
randomized to (mixture with or without Kenalog) and for 6 weeks.  Symptom 
questionnaires will be given at baseline, 3 weeks, and 6 weeks of treatment.  If the patient 
misses a study appointment, she will be called by telephone and queried about side effects 
and if appropriate, re-scheduled for an appointment.  
We plan to recruit patients from January 2019 until July 2020.  Patient follow up will be 
completed by September 2020.  As bladder instillations are commonly performed and 
considered low risk, no interim analysis will be performed.  Urinary tract infection will not 
be considered an adverse event related to study drug but will be monitored in data 
collection.
Sample size
Sample size calculation was based on the primary outcome, the O’Leary-Sant score on 
the final day of bladder instillation treatment as compared between the two treatment 
groups.  Based on previous studies, patients have a baseline IC/BPS score following 
standard medical treatment of approximately 24 ± 5.6 points.[16,17]   A 4.03 point 
decrease from baseline on the O’Leary-Sant questionnaire corresponds with at least a 
50% perceived improvement in the patient’s disease.[24]  We believe this level of 
difference between the groups in the final O’Leary-Sant scores would be clinically 
significant.  We want 80% power to detect a 4.03 point decrease from a baseline mean 
score of 24 (expected score in the bladder instillation without Kenalog group after 
treatment) with a standard deviation ≤ 5.6 points (alpha 0.05) with a 2-sided t-test.  The 
G*Power sample size calculator was used for the power calculations 
(https://www.stat.ubc.ca/~rollin/stats/ssize/n2.html) and these calculations were 
confirmed for accuracy by a University of Louisville biostatistician.  The resulting 
sample size was n= 32 for each group for a total of 64 enrolled patients.  Accounting for a 
20% dropout in the study, this would translate to a sample size of 80 patients enrolled 
with a goal of 40 per group.
Recruitment
Participants will be enrolled from the FPMRS clinics as noted above, at the time when a 
diagnosis of ICBPS is established (score ≥6 on either the symptom or the problem index 
of the O’Leary-Sant questionnaire) and the patient has expressed desire for bladder 
instillations as a therapy for this disorder. Recruited subjects will be given a sequential 
study ID number (SIDN) at the time of their informed consent, which cannot be changed 
or altered throughout their course in the study.
Methods:  Assignment of interventions
Allocation:
Sequence generation


Study Title:  Randomized controlled trial comparing two different bladder instillation treatments for interstitial 
cystitis/bladder pain syndrome.  
Protocol version:  January 23, 2019
Page 8 of 18
The randomization schedule will be created by an uninvolved statistician (not involved 
with study enrollment or data collection) using a random permutated block design 
(randomly varying from 6-10 patients per block with a 1:1 distribution within each block) 
to reduce predictability of a random sequence.  The statistician will provide the sequence 
to the medical assistant, who will correspond this to expected study ID numbers (SIDNs) 
of future subjects in the given sequence.  Study medications and packaging in agreement 
with this preset sequence will be made prior to the recruitment of that subject. 
Allocation concealment mechanism
The allocation concealment will be in the form of randomization, where only the 
biostatistician creating the allocation sequence and the medical assistant creating the study 
bladder instillation mixtures and are aware of the patient allocation.  As both of these 
parties are uninvolved in patient eligibility determination, recruitment, and direct patient 
care and follow up, this will maintain allocation concealment from the investigators.  Under 
no circumstances will the planned allocation for the patient be known at the time of 
recruitment.
Implementation
The investigators will enroll and consent eligible participants.  The participants will be 
given their study number.  This number will be tied to a bladder instillation mixture known 
to the medical assistant who will prepare the mixture but not to the study investigators or 
participants.  This number serves as the participant’s allocation.
Blinding (masking)
Patients and investigators will be blinded to treatment allocation, so this is a “double-blind” 
randomized, controlled trial.  
The patients, once consented, will be randomly assign to a treatment group by using the 
randomization sequence that was created by an uninvolved statistician.  The patients will 
use their SIDNs for the remainder of the study.  They are blinded to treatment because the 
study medications all look the same except for the syringe labeling with the patient’s SIDN.  
All patients will otherwise receive the same treatment and care.
The investigators are blinded because they are not privy to the bladder instillation mixture 
that the patient was assigned to and all patients are otherwise treated and assessed the same.
Unblinding (unmasking)
Should unblinding be warranted such as in exceptional circumstances when knowledge of 
the actual treatment is absolutely essential for further management of the patient, the ULH 
biotstatistician who has access to patient allocation, will be contacted to disclose to the 
principal investigator (PI) which treatment group the affected participant was assigned.  
The incident will be submitted on a case report form.
Methods:  Data collection, management, and analysis


Study Title:  Randomized controlled trial comparing two different bladder instillation treatments for interstitial 
cystitis/bladder pain syndrome.  
Protocol version:  January 23, 2019
Page 9 of 18
Data collection methods
All information will be obtained directly from questionnaires completed by the patient at 
the initial study visit, from contact points during study visits at which bladder instillations, 
are being performed, or at the end of the study at the 6th bladder instillation.  The patients 
will undergo bladder instillations at the University of Louisville Female Pelvic Medicine 
clinics either at the Spring Clinic location or the HCOC building, and data from validated 
questionnaires and medication compliance worksheets will be collected on paper at the 
appropriate time point.  Data will be extracted and entered into a RedCap or password-
protected Excel spreadsheet as outlined below.  No data will be extracted from the patient’s 
medical record or HCOC AllScripts electronic medical record system for this study; all 
data will be collected directly via study questionnaires and data report sheets designed for 
use in this study.
Retention and follow-up
We plan to query adverse events or side effects at each study visit.  We offer 
appointments three days a week to allow for optimal scheduling and will call patients if 
they are unable to make their follow up visit to ask about medication side effects as well 
as reschedule them for another appointment time.  They will be given written and verbal 
instructions on what to do in the event of side effects or adverse events to increase the 
likelihood of them presenting in person and communicating with their physician and/or 
study investigators about any issues.  Patients will be allowed to submit their interval and 
end-of-study questionnaires during their appointment visits.
Data Management
Data collection form:  See below and Appendix A
The following information will be collected directly from study questionnaires and entered 
into an encrypted excel spreadsheet: 

Study ID number (SIDN)

Name

Date of birth

Age

Race/ethnicity

Contact information

Emergency contact information (if patient willing to provide)

Social security number (SSN)

Weight

Body mass index (BMI)

Smoking status

Gravidity 

Parity


Study Title:  Randomized controlled trial comparing two different bladder instillation treatments for interstitial 
cystitis/bladder pain syndrome.  
Protocol version:  January 23, 2019
Page 10 of 18

Reason for visit

Prior pelvic reconstructive surgery

Medical history, specifically history of: irritable bowel syndrome, fibromyalgia, 
chronic pain, chronic pelvic pain, vulvodynia, anxiety, depression, chronic fatigue 
syndrome

Charleston comorbidity index[25]

O’Leary-Sant questionnaire (problem and symptom index scores)[16,17]

Pelvic pain and urgency/frequency (PUF) questionnaire[18]

Overactive Bladder Questionnaire (OABq)[19]

Pelvic floor distress inventory (PFDI)[20]

Sexual function measured by the Pelvic Organ Prolapse Incontinence Sexual 
Questionnaire, IUGA-Revised (PISQ-IR) questionnaire[21-23]

Visual Analogue Scale (VAS) for pain 

Timing and nature of adverse events during the study, regardless of suspected or 
known relationship to study medication
Data Handling/Storage:
All identifying information and data collected during the course of this study will be kept 
secure and strictly confidential. All data will be stored electronically on a password 
protected, encrypted laptop in the possession of the study investigator.  Risks for breaches 
of confidentiality will be minimized by entering data from the medical record to a password 
protected, encrypted computer database which will have limited access to the PI.
The patient’s unique study ID will be used for storage, analysis and publication. 
Paper data collections forms will be utilized and data will be entered from the paper data 
form by a study investigator into either a RedCap database or an encrypted, password 
protected laptop or computer Excel database.  These data forms will be housed in a locked 
file cabinet in the Division of Female Pelvic Medicine and Reconstruction office in a 
locked cabinet with restricted access. 
Data Analysis and Statistical Methods:
The data will be analyzed in consultation with a department-committed biostatistician 
utilizing SPSS statistical software.  Categorical variables (e.g. 'yes" to certain questions 
on the PFDI) will be compared using chi-square tests (or Fisher's exact test when 
appropriate).  Continuous variables (such as primary outcome) will be compared using t-
tests, and changes in continuous outcomes over time (e.g. change from baseline to 8-
week O'Leary-Sant score) will be compared with paired t-tests.  A regression analysis 
will be performed to determine the impact of various relevant cofactors (e.g. patient age, 
presence of other chronic disorders, level of OAB symptoms) on the relationship between 
group assignment and treatment outcomes.  
We will perform an intention-to-treat analysis by the assigned study groups for the initial 
analysis, comparing women who followed up at the completion of the study (6-week 
outcomes) between the study groups (bladder instillations with and without Kenalog) as 


Study Title:  Randomized controlled trial comparing two different bladder instillation treatments for interstitial 
cystitis/bladder pain syndrome.  
Protocol version:  January 23, 2019
Page 11 of 18
assigned.  We will also perform a per-protocol analysis, comparing women in the bladder 
instillation with Kenalog who had at least 4 bladder instillation treatments to the group 
that had bladder instillations without Kenalog.  Lastly, we will perform two types of 
sensitivity analysis:
(1) Imputation of missing data with assumption of treatment non-response (baseline 
O’Leary-Sant and other outcomes scores carried forward as the final outcome)
(2) Imputation of missing data with assumption of “best last known” response (final 
outcomes assumed to be the best value for that outcome during the study course 
that was available)
(3) Imputation of missing data with “most recent last known” response (final 
outcomes assumed to be the most recent value for that outcome during the study 
course that was available)
Planned secondary analyses will include: (1) treatment response of subgroups of patients 
with and without prominent OAB symptoms (OABq score ≥ 8); (2) treatment response in 
patients with and without a history of prior IC/BPS treatment; and (3) the relationship 
between known coexisting pain and irritative organ disorders (irritable bowel syndrome, 
fibromyalgia, chronic pain, chronic pelvic pain, vulvodynia, anxiety, depression, chronic 
fatigue syndrome) and response to treatment; (4) Treatment cost-analysis.  The 
interaction of these factors (prominent OAB symptoms, prior IC/BPS treatment, 
coexisting pain or irritative organ disorders) with the relationship between randomization 
and treatment response will be determined.  
Potential Benefits:
Participants may benefit from the multiple agents in the bladder instillation, including 
Kenalog, a steroid.  Steroids have been shown to be helpful in patients with IC/BPS.  
Bladder instillation therapy is a well-tolerated and commonly used treatment of IC/BPS. 
Potential Risks: 
This research study cannot practically be conducted without access and use of protected 
health information.  Thus, the principle risk to patients involved in the study is a potential 
breach of confidentiality and misuse or exposure of this information.  With this in mind, 
the investigators will conduct all research activities in such a way that maximizes data 
security and minimizes any risk of potential data breaches.
Patients may have risk of embarrassment or offense due to the private and personal nature 
of some of the study questions (e.g. such as questions about urinary incontinence or sexual 
activity).  This risk will be minimized by accurate description of the nature of the study 
and the study outcomes to the patient prior to informed consent, and communication with 
the patient regarding the right to decline to answer any given study question.
Prior to offering enrollment in the study, the patient must desire bladder instillation therapy 
for treatment of her IC/BPS symptoms.  The standard practice of bladder instillations is to 
cleanse the external urethral meatus with betadine or another appropriate cleansing 
solution.  This, as well as the insertion of a small bladder catheter, can sometimes be 
uncomfortable for patients.  Sometimes the instillation solution can be uncomfortable for 


Study Title:  Randomized controlled trial comparing two different bladder instillation treatments for interstitial 
cystitis/bladder pain syndrome.  
Protocol version:  January 23, 2019
Page 12 of 18
patients due their IC/BPS symptoms and the expansion of their bladders.  These potential 
risks and discomforts are not over and above that experienced in a standard visit to this 
clinical service.  That being said, there may be ways to reduce the occasional discomfort 
of undergoing a bladder instillations, such as using topical lidocaine gel for insertion of the 
bladder catheter and instilling the solution into the bladder slowly.   Another potential risk 
is an allergic reaction to the ingredients in the bladder instillations.  Although women with 
known hypersensitivity will be excluded, women may have unknown or new sensitivity to 
the medications.  These are highly unlikely to be serious and are reversible on stopping use 
of medication.  Patients will have the study personnel’s contact information should they 
develop any adverse events prior to their weekly visit and need medical attention.    
Methods:  Monitoring
Data monitoring:
As this study has minimal risk, a Data Safety Monitoring Board (DSMB) is not required.  
However, the study participants will be given numbers to reach the principal investigator, 
clinic, or after-hours answering service should they experience any side effects or adverse 
events related to the study.  They will be advised to seek care from their doctor for 
medical advice related or unrelated to the study, and the study investigators will alert the 
University of Louisville IRB apprised of all adverse events experienced by trial patients, 
regardless of severity or clinical belief of relation to the study drug.  If an adverse event is 
sufficiently severe enough to merit stopping the study drug temporarily or permanently, 
we will work in collaboration with the IRB to determine if patient randomization should 
be revealed.  This determination will come after the drug has been stopped and 
appropriate medical attention given to the patient.  Serious, drug-related adverse events 
will be those that require intravenous medication, hospital admission, or procedural 
intervention and are considered to be directly associated with study treatment.  If ≥ 25% 
of patients have experienced an adverse event thought to be related to the study drug or if 
≥ 10% of patients have experienced a serious adverse event related to the study drug, the 
study will be terminated early.  
Harms:
Adverse event and unintended effects of trial interventions or trial conduct with be 
managed by a Research Nurse, and the investigators.  Such information will be both 
solicited and participants will be encouraged to spontaneously report such effects.  The 
research team will closely monitor data collection and assure confidentiality at every point 
during this study. The IRB and appropriate hospital research office will be notified 
immediately of any adverse events, including security breaches of the data, or UPIRTSOs, 
whether expected or unexpected.  Participants will discontinue the products if they have an 
allergic reaction to the medication or any of its components.  The worse anticipated adverse 
reaction is discomfort with bladder instillation which would be monitored, recorded, and 
responded to by either our Research Nurse or the patient’s chosen provider.   
The individual stopping criteria are severe allergic reactions and events that require 
intravenous medication, hospital admission, or procedural intervention and are considered 
to be directly associated with the bladder instillations.  Allergic reactions will be skin 


Study Title:  Randomized controlled trial comparing two different bladder instillation treatments for interstitial 
cystitis/bladder pain syndrome.  
Protocol version:  January 23, 2019
Page 13 of 18
reactions such as ulcers; rashes; and swelling and anaphylactic reaction to the bladder 
instillations.  As noted above, monitoring of adverse events via study investigators and the 
IRB will be performed.
 
The investigators will be responsible for ensuring participants' safety on a weekly 
basis.  The investigators will monitor participant safety, evaluate the progress of the study, 
to review procedure for maintaining the confidentiality of data, quality of data collection, 
management, participant safety, and analyses on a monthly basis at our research 
meetings.  The PI will be informed of serious adverse events as soon as they occur and will 
notify the research nurse or the other investigators within 24 hours of notification.  The 
participants will be given a number to call the office or the answering service to contact 
the PI in the event of an adverse reaction.  Adverse reactions will be documented according 
the guidelines set forth by the US Dept. of Health and Human Services. 
Auditing:
Auditing will be at the discretion of the IRB.
Ethics and dissemination
Research ethics approval:
This study will be reviewed and approved by the University of Louisville Institutional 
Review Board.  
Protocol amendments:
Important protocol modifications, such as, changes eligibility criteria, outcomes, analysis, 
to relevant parties (investigators, trial participants, clinicaltrial.gov).  The research 
personnel involved in this study Dr. Kate Meriwether, Dr. Sean Francis, Dr. Olivia 
Cardenas-Trowers, Dr. James R. Stewart, and Dr. Ankita Gupta are CITI and HIPAA 
trained. No additional personnel are involved at this time. If new research personnel are 
added to the study, an amendment will be submitted to and approved by the IRB before 
being allowed to participate in the study.
Consent or assent:
Informed consent from potential trial participants or authorized surrogates will be obtained 
before enrollment.  There is a possibility that the participants’ data could be used in an 
ancillary study, and this will be disclosed to patients and part of the informed consent 
language.
Confidentiality:
The investigators will take great care to protect and secure all study data collected for this 
study.  Risks for breaches of confidentiality will be minimized by entering data from the 
medical record or paper data collection forms to a password protected, encrypted computer 
database which will have limited access to the PI, Co-PIs, and sub-investigators.


Study Title:  Randomized controlled trial comparing two different bladder instillation treatments for interstitial 
cystitis/bladder pain syndrome.  
Protocol version:  January 23, 2019
Page 14 of 18
Personal identifiers (name, DOB, contact information for patient and an emergency contact 
person, and social security number) will be collected and retained in the event of need to 
contact patients with clarification of questionnaire responses, urgent study alerts, or early 
termination of the study by the investigators. However, all study information will be 
completely de-identified by using a study code or number instead of identifiers for the 
purposes of data analysis and reporting.
Data will be de-identified as soon as is feasible without compromising the study.  Data will 
be stored as an encrypted file on a password protected laptop computer or password 
protected shared U of L drives, ULP share point server or secure hospital database. Data 
will NOT be stored on a ‘cloud’ type server per HIPAA regulations.  
A de-identified Excel spreadsheet will be provided to the statistician for statistical analysis.  
Statistical consultants on this study will only work with totally de-identified data and will 
never see patient identifying information, patient images, or patient medical records.  
The protected health information gathered for this study will be destroyed as soon as is 
feasible and will not be reused or disclosed to any other person or entity, except as required 
by law.   The Excel “key” spreadsheet listing Research ID #, name, DOB, contact 
information for patient and emergency contact, and SSN will be kept distinct from the 
remainder of the study information as a means to contact patients or identify the patient as 
needed for safety, medical care, or study-wide alerts.  As soon as all data have been 
collected and there is no further need to return to a subject’s contact information and 
identifying information, the Excel key(s) linking name, DOB, contact information, and 
SSN to study ID numbers (SIDNs) will be destroyed.  
Declaration of interests:
The PI does not have any financial disclosures or competing interests for the overall trial.  
Access to data:
The PI and co-investigators will have access to the de-identified final trial dataset.  Only 
the investigator, Olivia Cardenas-Trowers, who is performing data entry and management 
for this study, will have access to the password-protected key that allows identification or 
contact of the individual patient as related to their SIDN.
Ancillary and post-trial care:
We do not anticipate any major harm or complications due to use of the products.  We do 
not foresee any long-term sequelae from the bladder instillations.
Dissemination policy:
The investigators intend to publish the results obtained from this trial.  All the investigators 
are eligible for authorship.  No professional writers will be used for the publication.
Appendices
1. Informed consent


Study Title:  Randomized controlled trial comparing two different bladder instillation treatments for interstitial 
cystitis/bladder pain syndrome.  
Protocol version:  January 23, 2019
Page 15 of 18
2. Data collection spread sheet (Microsoft Excel)
3. Contact information and patient identification sheet (Appendix A)
4. Patient health history and characteristics questionnaire (Appendix B)
5. O’Leary-Sant questionnaire (problem and symptom index scores)[16,17] 
(Appendix C)
6. Pelvic pain and urgency/frequency (PUF) questionnaire[18] (Appendix D)
7. Overactive Bladder Questionnaire (OABq)[19] (Appendix E)
8. Pelvic floor distress inventory (PFDI)[20] (Appendix F)
9. Pelvic Organ Prolapse Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-
IR) questionnaire[21-23] (Appendix G)
10. Visual Analogue Scale (VAS) for pain (Appendix H)
11. Medication compliance/pill count, adverse event, and medical event reporting 
worksheet (Appendix I)


Study Title:  Randomized controlled trial comparing two different bladder instillation treatments for interstitial 
cystitis/bladder pain syndrome.  
Protocol version:  January 23, 2019
Page 16 of 18
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Protocol version:  January 23, 2019
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