Overactive Bladder, Painful Bladder Syndrome, Urinary Bladder, Neurogenic, Urinary Urge Incontinence
Conditions
Brief summary
The purpose of this study is to test whether using belladonna & opiate suppositories (B&Os) can improve patient discomfort during Onabotulinumtoxin A (BoNT) injection into the bladder for treatment of overactive bladder, neurogenic detrusor overactivity, or interstitial cystitis.
Interventions
DRUGOnabotulinumtoxin A (BoNT)
DRUGbelladonna
Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.
DRUGMorphine
Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.
DRUGPlacebo
matching placebo to B&O suppository
DRUGActive B&O suppository of belladonna
belladonna 16.2mg and morphine 7.5mg
Sponsors
Edgar LeClaire, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Met clinical criteria under outside care or during the Principal Investigator's routine standard of care for BoNT injection therapy * No contraindication to BoNT therapy as outlined by drug manufacturer guidelines * Participants have elected to have the BoNT injection therapy prior to being offered enrollment into the study for either overactive bladder (OAB), neurogenic detrusor overactivity (NDO), or refractory interstitial cystitis (IC)
Exclusion criteria
* Currently pregnant * Currently nursing a baby * Anticipated geographic relocation within the first 3 months following treatment * Allergy to morphine, belladonna, or opiates * Patients will 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Bladder Injection Pain | Baseline and intraoperative | The primary outcome will be calculated difference in numeric rating scale (NRS) pain score prior to procedure and midway through procedure. Scale is one question and has a range from a score of 0 (no pain) to 10 (worst possible pain). Measure will be reported as the intraoperative pain score minus the preoperative pain score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-operative Pain Score | Postoperative (within 10 minutes of the end of the BoNT procedure) | Measured using NRS. Scale is one question and has a range from a score of 0 (no pain) to 10 (worst possible pain). |
| Number of Participants Declining to Complete Procedure Due to Pain Intolerance | Intraoperative | Number of patients that decline to proceed with entire procedure (20 injections) due to pain or discomfort. |
| Postoperative Voiding Trial Results | Postoperative (before leaving the clinic, within 3 hours of the end of the BoNT procedure) | Distribution of patients with postoperative volume in ml of post-void residual urine obtained via catheter greater than 200ml. |
| Pre-analgesia Pain Score | Baseline | Measured using NRS. Scale is one question and has a range from a score of 0 (no pain) to 10 (worst possible pain). |
| Number of Participants With Evidence of Infection or Positive Urine Culture | 2 Weeks | Urinalysis results showing evidence of infection or positive urine culture at 2-week follow-up appointment. |
| Participant Satisfaction With Pain Control | Postoperative (within 10 minutes of the end of the BoNT procedure) | Measured using one question Likert scale. This will be a 4-level scale ranging from 'not at all satisfied,' 'slightly satisfied,' 'mostly satisfied,' and 'very much satisfied.' |
| Post Void Residual (PVR) | 2 Weeks | Distribution of patients with volume in ml of post-void residual urine obtained via catheter greater than 200 ml at 2-week follow-up appointment. |
Countries
United States
Participant flow
Recruitment details
Recruitment began December 1, 2015 at a private urogynecology clinic. There were 32 patients that were assessed for eligibility. Four patients were excluded: three patients did not meet inclusion criteria (did not proceed with in-office treatment) and one patient declined to participate due to wanting the active suppository.
Pre-assignment details
28 patients consented to participate in the study. Two patients withdrew consent to participate and did not end up participating: one patient's medication resumed efficacy, and one patient withdrew regarding possible use of narcotics and concern due to a a previous narcotic addition. Thus, only 26 patients are considered enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Active B&O Suppository of Belladonna Receive the B&O suppository (belladonna/morphine) 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.
Onabotulinumtoxin A (BoNT)
belladonna: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.
Morphine: Part of dosage of the compounded active B&O suppository of belladonna 16.2mg and morphine 7.5mg.
Active B&O suppository of belladonna: belladonna 16.2mg and morphine 7.5mg | 13 |
| Placebo Suppository Receive a placebo suppository 40 minutes prior to Onabotulinumtoxin A (BoNT) injection procedure in conjunction with local analgesia.
Onabotulinumtoxin A (BoNT)
Placebo: matching placebo to B&O suppository | 13 |
| Total | 26 |
Baseline characteristics
| Characteristic | Active B&O Suppository of Belladonna | Placebo Suppository | Total |
|---|---|---|---|
| Age, Continuous | 73.62 years STANDARD_DEVIATION 10.25 | 65.54 years STANDARD_DEVIATION 10.22 | 69.58 years STANDARD_DEVIATION 10.84 |
| Body mass index | 35.45 kg/m^2 STANDARD_DEVIATION 11.34 | 34.19 kg/m^2 STANDARD_DEVIATION 6.33 | 34.82 kg/m^2 STANDARD_DEVIATION 9.02 |
| Current smoker | 1 Participants | 1 Participants | 2 Participants |
| Estrogen use Oral estrogen | 2 Participants | 1 Participants | 3 Participants |
| Estrogen use Vaginal estrogen | 4 Participants | 7 Participants | 11 Participants |
| Gynecologic disorders/diagnoses Chronic cystitis | 3 Participants | 2 Participants | 5 Participants |
| Gynecologic disorders/diagnoses Constipation | 1 Participants | 2 Participants | 3 Participants |
| Gynecologic disorders/diagnoses Cystocele | 0 Participants | 3 Participants | 3 Participants |
| Gynecologic disorders/diagnoses Rectocele | 0 Participants | 1 Participants | 1 Participants |
| Gynecologic disorders/diagnoses Uterine prolapse | 0 Participants | 0 Participants | 0 Participants |
| Gynecologic disorders/diagnoses Vaginal vault prolapse | 1 Participants | 2 Participants | 3 Participants |
| Gynecologic disorders/diagnoses Vulvovaginal atrophy | 7 Participants | 7 Participants | 14 Participants |
| Medication use Diuretic medication | 1 Participants | 4 Participants | 5 Participants |
| Medication use Narcotic medication | 1 Participants | 1 Participants | 2 Participants |
| Medication use Steroid medication | 1 Participants | 0 Participants | 1 Participants |
| Medication use in Last 24 Hours Neuromodulator medication | 1 Participants | 1 Participants | 2 Participants |
| Medication use in Last 24 Hours Nonsteroidal anti-inflammatory drugs (NSAIDs) | 5 Participants | 6 Participants | 11 Participants |
| Medication use in Last 24 Hours Opioid medication | 2 Participants | 1 Participants | 3 Participants |
| Medication use in Last 24 Hours Sedative medication | 1 Participants | 5 Participants | 6 Participants |
| Medication use in Last 24 Hours Selective serotonin reuptake inhibitors (SSRIs) | 7 Participants | 0 Participants | 7 Participants |
| Menopausal | 13 Participants | 12 Participants | 25 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 13 Participants | 26 Participants |
| Sex: Female, Male Female | 13 Participants | 13 Participants | 26 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Surgical history Back or spinal surgery | 3 Participants | 2 Participants | 5 Participants |
| Surgical history Bilateral salpingo-oophorectomy (BSO) | 6 Participants | 7 Participants | 13 Participants |
| Surgical history Hysterectomy | 10 Participants | 10 Participants | 20 Participants |
| Surgical history Laparotomy | 5 Participants | 5 Participants | 10 Participants |
| Surgical history Previous sling procedure | 3 Participants | 3 Participants | 6 Participants |
| Surgical history Prolapse surgery with mesh | 0 Participants | 1 Participants | 1 Participants |
| Surgical history Prolapse surgery without mesh | 2 Participants | 3 Participants | 5 Participants |
| Vaginal parity | 2 pregnancies | 3 pregnancies | 2 pregnancies |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 12 | 0 / 25 |
| other Total, other adverse events | 2 / 13 | 4 / 12 | 6 / 25 |
| serious Total, serious adverse events | 0 / 13 | 0 / 12 | 0 / 25 |
Outcome results
Primary
Change in Bladder Injection Pain
The primary outcome will be calculated difference in numeric rating scale (NRS) pain score prior to procedure and midway through procedure. Scale is one question and has a range from a score of 0 (no pain) to 10 (worst possible pain). Measure will be reported as the intraoperative pain score minus the preoperative pain score.
Time frame: Baseline and intraoperative
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active B&O Suppository of Belladonna | Change in Bladder Injection Pain | 5 units on a scale |
| Placebo Suppository | Change in Bladder Injection Pain | 4 units on a scale |
| Total | Change in Bladder Injection Pain | 5 units on a scale |
p-value: 0.94Kruskal-Wallis
Secondary
Number of Participants Declining to Complete Procedure Due to Pain Intolerance
Number of patients that decline to proceed with entire procedure (20 injections) due to pain or discomfort.
Time frame: Intraoperative
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active B&O Suppository of Belladonna | Number of Participants Declining to Complete Procedure Due to Pain Intolerance | 0 Participants |
| Placebo Suppository | Number of Participants Declining to Complete Procedure Due to Pain Intolerance | 0 Participants |
| Total | Number of Participants Declining to Complete Procedure Due to Pain Intolerance | 0 Participants |
Secondary
Number of Participants With Evidence of Infection or Positive Urine Culture
Urinalysis results showing evidence of infection or positive urine culture at 2-week follow-up appointment.
Time frame: 2 Weeks
Population: One patient did not complete 2-week follow-up appointment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active B&O Suppository of Belladonna | Number of Participants With Evidence of Infection or Positive Urine Culture | 2 Participants |
| Placebo Suppository | Number of Participants With Evidence of Infection or Positive Urine Culture | 4 Participants |
| Total | Number of Participants With Evidence of Infection or Positive Urine Culture | 6 Participants |
Secondary
Participant Satisfaction With Pain Control
Measured using one question Likert scale. This will be a 4-level scale ranging from 'not at all satisfied,' 'slightly satisfied,' 'mostly satisfied,' and 'very much satisfied.'
Time frame: Postoperative (within 10 minutes of the end of the BoNT procedure)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Active B&O Suppository of Belladonna | Participant Satisfaction With Pain Control | Not at all satisfied | 0 Participants |
| Active B&O Suppository of Belladonna | Participant Satisfaction With Pain Control | Slightly satisfied | 2 Participants |
| Active B&O Suppository of Belladonna | Participant Satisfaction With Pain Control | Mostly satisfied | 2 Participants |
| Active B&O Suppository of Belladonna | Participant Satisfaction With Pain Control | Very much satisfied | 9 Participants |
| Placebo Suppository | Participant Satisfaction With Pain Control | Very much satisfied | 6 Participants |
| Placebo Suppository | Participant Satisfaction With Pain Control | Not at all satisfied | 1 Participants |
| Placebo Suppository | Participant Satisfaction With Pain Control | Mostly satisfied | 5 Participants |
| Placebo Suppository | Participant Satisfaction With Pain Control | Slightly satisfied | 1 Participants |
| Total | Participant Satisfaction With Pain Control | Very much satisfied | 15 Participants |
| Total | Participant Satisfaction With Pain Control | Slightly satisfied | 3 Participants |
| Total | Participant Satisfaction With Pain Control | Mostly satisfied | 7 Participants |
| Total | Participant Satisfaction With Pain Control | Not at all satisfied | 1 Participants |
Secondary
Post-operative Pain Score
Measured using NRS. Scale is one question and has a range from a score of 0 (no pain) to 10 (worst possible pain).
Time frame: Postoperative (within 10 minutes of the end of the BoNT procedure)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active B&O Suppository of Belladonna | Post-operative Pain Score | 2 units on a scale |
| Placebo Suppository | Post-operative Pain Score | 3 units on a scale |
| Total | Post-operative Pain Score | 2 units on a scale |
Secondary
Postoperative Voiding Trial Results
Distribution of patients with postoperative volume in ml of post-void residual urine obtained via catheter greater than 200ml.
Time frame: Postoperative (before leaving the clinic, within 3 hours of the end of the BoNT procedure)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active B&O Suppository of Belladonna | Postoperative Voiding Trial Results | 3 Participants |
| Placebo Suppository | Postoperative Voiding Trial Results | 5 Participants |
| Total | Postoperative Voiding Trial Results | 8 Participants |
Secondary
Post Void Residual (PVR)
Distribution of patients with volume in ml of post-void residual urine obtained via catheter greater than 200 ml at 2-week follow-up appointment.
Time frame: 2 Weeks
Population: One patient did not complete 2-week follow-up post-void residual exam.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active B&O Suppository of Belladonna | Post Void Residual (PVR) | 2 Participants |
| Placebo Suppository | Post Void Residual (PVR) | 3 Participants |
| Total | Post Void Residual (PVR) | 5 Participants |
Secondary
Pre-analgesia Pain Score
Measured using NRS. Scale is one question and has a range from a score of 0 (no pain) to 10 (worst possible pain).
Time frame: Baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active B&O Suppository of Belladonna | Pre-analgesia Pain Score | 0 units on a scale |
| Placebo Suppository | Pre-analgesia Pain Score | 0 units on a scale |
| Total | Pre-analgesia Pain Score | 0 units on a scale |