Detrusor Hyperreflexia, Overactive Bladder, Urge Incontinence, Urinary Incontinence, Urinary Urge Incontinence
Conditions
Keywords
OAB, Over Active Bladder, overactive bladder, Urinary Urge Incontinence, Urinary Incontinence, Botox, DMSO, bladder instillation, instillation, detrusor hyperreflexia, urge incontinence
Brief summary
The purpose of this study is to determine whether women with overactive bladder (OAB) who receive direct instillation via a catheter of a Botulinum-A Toxin (Botox) with Dimethyl Sulfoxide (DMSO) solution experience significantly better improvement of their OAB symptoms when compared to a similar group of women with OAB who receive instillation of DMSO only.
Detailed description
The primary objective of this study is to evaluate the efficacy of catheter-based instillation of a solution of Botox/DMSO as a novel method for treating women with overactive bladder (OAB) and secondary urinary incontinence who have failed oral pharmacologic therapy. This study will test the broad hypothesis that administration of Botox/DMSO instillations into the bladder with a urethral catheter can significantly improve symptoms and quality of life in patients with OAB when compared to DMSO installations alone. Explicitly, we hypothesize that scores on the validated Incontinence Quality of Life (I-QOL) questionnaire of women with OAB who receive Botox/DMSO instillation will be much improved at three-month follow-up compared to similar women receiving DMSO instillation alone. Our long-term goal is to offer women with detrusor hyperreflexia or OAB a less invasive alternative to surgery and an alternative to anticholinergic by mouth medications. In support of this effort, we are proposing a randomized, double-blind, placebo controlled clinical trial to be conducted in the Department of Urology at Mayo Clinic, Jacksonville, Florida. Note: The study was terminated early in July of 2011 due to an extended medical absence of the Principal Investigator.
Interventions
DRUGBotox Instillation
Botox instilled into the bladder via ureteral catheter and retained for up to 30 minutes then spontaneously voided.
DRUGDMSO Instillation
DMSO 50% w/w aqueous solution; 50 cubic centimeters instilled into the bladder via ureteral catheter and retained up to 30 minutes then spontaneously voided.
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female patient aged 18 years or older * No evidence of stress urinary incontinence on physical examination or urodynamics * Patients who have failed prior drug therapy for overactive bladder or detrusor hyperreflexia * Patients with symptoms and signs of OAB, detrusor hyperreflexia, urinary urgency, urinary urge incontinence. * Patient who is mentally competent with the ability to understand and comply with the requirements of the study * Patient who agrees to be available for the follow-up evaluations as required by the protocol * Patient who has given signed informed consent
Exclusion criteria
* Patient with Post-Void Residual Urine (PVRU) greater than 100 ml on repeated measures. (Patient with a single PVRU of \>100 ml and followed by two consecutive PVRU measurements of \<100 ml may be included in the study) * Patient with greater than vesicoureteral reflux grade 1, interstitial cystitis, genitourinary fistulae * Patient with pelvic organ prolapse stage III or IV, i.e. the most distal part of the prolapse protruding more than 1 cm beyond the hymen (\>+1), at straining * Patient with un-investigated hematuria * Patient with lower tract genitourinary malignancies * Patient on current medication for stress urinary incontinence, such as alpha-adrenergic agonists or duloxetine, within three weeks prior to completing the baseline Bladder Diary (estrogen therapy on a stable dose for at least two months prior to study start is allowed) * Patient with ongoing complications of prior anti-incontinence surgery * Patient who is pregnant, lactating, or planning to become pregnant within the study period * Patient who has received pelvic radiation * Patient with any condition, which could lead to significant postoperative complications, including current infection and uncontrolled diabetes. * Patient who is morbidly obese (defined as BMI \> 40 Kg/m2) * Patient who is bedridden, institutionalized or in such physical condition that she cannot move to the closest bathroom without assistance from another person * Patient with current or acute urinary tract infection, including cystitis or urethritis. (Patient with such infections should be treated with antibiotics, with subsequent urinalysis tests confirming the absence of such infection before study inclusion) * Patient with any condition that would preclude treatment due to contraindications and/or warnings in the study product's labeling * Patient on immunomodulatory therapy (suppressive or stimulatory) * Patient with known lidocaine hypersensitivity or hypersensitivity to any anesthetics to be used during the treatment session/surgical procedure * Patient with a concurrent use of another study product within two weeks prior to study start, or who concurrently participate in any other clinical study * Any disease that in the opinion of the Investigator would make the patient unsuitable for the study * Patient with a life expectancy of less than 12 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Incontinence Quality of Life (I-QoL) Score | Baseline, 1 month, 3 months | The I-QoL measures the effect of urinary incontinence on quality of life. It is divided into 3 subscales: 1) avoidance and limiting behavior, 2) psychosocial impact, and 3) social embarrassment. The I-QOL is comprised of 22 items, each with the response scale from '1= Extremely' to '5= Not at all'. A mean score for each subscale is calculated (averaging the scores for the items in each subscale) as well as a total score for all 22 items (sum of all subscale scores). The scores are then transformed to a 'Scale score' ranging from 0-100 points for ease of interpretation: Scale score = (sum of the items - lowest possible score)/possible raw score range X 100. Higher scores indicate less impact of incontinence on quality of life. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Incontinence Impact Questionnaire Short Form (IIQ-7) | baseline, 1 month, 3 months | The IIQ-7 measures the effect of urinary incontinence on quality of life. It is comprised of 7 items, each with the response scale from 0=Not at all to 3=Greatly. The scores can range from 0 to 21; a low score indicates less impact of incontinence on quality of life. |
| Change in International Consultation on Incontinence Questionnaire - Short Form Score (ICIQ-SF) | baseline, 1 month, 3 months | The ICIQ-SF provides a brief and robust measure to assess the impact of symptoms of incontinence on quality of life and outcome of treatment. The questionnaire has 4 items and the score can range from 0 to 21, with greater values indicating increased severity of symptoms and lower quality of life. |
| Change in Urogenital Distress Inventory (UDI-6) | baseline, 1 month, 3 months | The UDI-6 measures the effect of urinary incontinence on quality of life. It consists of 6 items, each with the response scale from 0=Not at all to 3=Greatly. The scores can range from 0 to 18; a low score indicates less impact of incontinence on quality of life. |
| Number of Participants With Decrease in Blaivas-Groutz Anti-Incontinence Score at 1 Month and 3 Months | baseline, 1 month, 3 months | The Blaivas-Groutz Anti-incontinence scale was used as a measure of urinary incontinence. This scale combines information on the number of incontinent episodes in a 24-hour period, 24-hour pad weights, and a qualitative rating by the patient into a single score ranging from 0 to 6. this score is then used to categorize incontinence as none (0), mild (1-2), moderate (3-4), or severe (5-6). |
| Number of Participants With a Decrease in Urinary Urgency at 1 Month and 3 Months | Baseline, 1 month, 3 months | Urinary urgency was measured by the Indevus Urgency Severity Scale (IUSS). The IUSS asks patients to assess the severity of 'urgency' at each void. The scale employs the following wording: Degree of urgency is meant to describe your urge to urinate. Sometimes you may feel a very strong urge to urinate and at other times, you may feel a milder urge prior to the onset of a toilet void. Rate this feeling by circling 0, 1, 2, or 3, defined as: 0: NONE - no urgency, 1: MILD - awareness of urgency, but it is easily tolerated and you can continue with your usual activity or tasks, 2: MODERATE - enough urgency discomfort that it interferes with or shortens your usual activity or tasks, 3: SEVERE - extreme urgency discomfort that abruptly stops all activity or tasks. |
Countries
United States
Participant flow
Recruitment details
A total of 25 subjects were recruited from 10/21/2008 to 8/19/2010. Three of these were determined to be screen failures before randomization, and another one was withdrawn prior to randomization. Twenty one subjects were randomized: 11 to Botox/DMSO, and 10 to DMSO only.
Participants by arm
| Arm | Count |
|---|---|
| Botox and DMSO Instillation Botulinum-A Toxin (Botox) 300 units in 50 cubic centimeters of Dimethyl Sulfoxide (DMSO) 50% w/w aqueous solution
Botox Instillation: Botox instilled into the bladder via ureteral catheter and retained for up to 30 minutes then spontaneously voided.
DMSO Instillation: DMSO 50% w/w aqueous solution; 50 cubic centimeters instilled into the bladder via ureteral catheter and retained up to 30 minutes then spontaneously voided. | 11 |
| DMSO Instillation Dimethyl Sulfoxide (DMSO) 50% w/w aqueous solution, 50 cubic centimeters
DMSO Instillation: DMSO 50% w/w aqueous solution; 50 cubic centimeters instilled into the bladder via ureteral catheter and retained up to 30 minutes then spontaneously voided. | 10 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | DMSO Instillation | Total | Botox and DMSO Instillation |
|---|---|---|---|
| Age, Continuous | 71 years | 68 years | 58 years |
| Body Mass Index | 30 kg/m^2 | 27 kg/m^2 | 26 kg/m^2 |
| History of Hypertension Hypertension | 7 participants | 13 participants | 6 participants |
| History of Hypertension No hypertension | 3 participants | 8 participants | 5 participants |
| History of Urinary Tract Infections (UTIs) No previous UTIs | 0 participants | 1 participants | 1 participants |
| History of Urinary Tract Infections (UTIs) Previous history of UTIs | 10 participants | 20 participants | 10 participants |
| Incontinent Episodes during 24 Hours | 3 Episodes | 4 Episodes | 6 Episodes |
| Median 24 Hour Pad Weight | 179 g | 166 g | 166 g |
| Median Number of Pads Per Day | 5 pads | 5 pads | 4 pads |
| Number of Vaginal Births 0 vaginal births | 3 participants | 6 participants | 3 participants |
| Number of Vaginal Births 1-2 vaginal births | 1 participants | 5 participants | 4 participants |
| Number of Vaginal Births ≥ 3 vaginal births | 6 participants | 10 participants | 4 participants |
| Post-Void Residual Urine | 29 mL | 17 mL | 15 mL |
| Region of Enrollment United States | 10 participants | 21 participants | 11 participants |
| Sex: Female, Male Female | 10 Participants | 21 Participants | 11 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Smoking Status Current smoker | 0 participants | 1 participants | 1 participants |
| Smoking Status Never smoked | 6 participants | 10 participants | 4 participants |
| Smoking Status Past smoker | 4 participants | 10 participants | 6 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 11 | 7 / 10 |
| serious Total, serious adverse events | 0 / 11 | 2 / 10 |
Outcome results
Primary
Change in Incontinence Quality of Life (I-QoL) Score
The I-QoL measures the effect of urinary incontinence on quality of life. It is divided into 3 subscales: 1) avoidance and limiting behavior, 2) psychosocial impact, and 3) social embarrassment. The I-QOL is comprised of 22 items, each with the response scale from '1= Extremely' to '5= Not at all'. A mean score for each subscale is calculated (averaging the scores for the items in each subscale) as well as a total score for all 22 items (sum of all subscale scores). The scores are then transformed to a 'Scale score' ranging from 0-100 points for ease of interpretation: Scale score = (sum of the items - lowest possible score)/possible raw score range X 100. Higher scores indicate less impact of incontinence on quality of life.
Time frame: Baseline, 1 month, 3 months
Population: Analysis was done according to the principle of intention-to-treat. The sample size was reduced to 9 in the Dimethyl Sulfoxide (DMSO) instillation arm at 3 months due to withdrawal for reasons unrelated to study (cancer).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botox and DMSO Instillation | Change in Incontinence Quality of Life (I-QoL) Score | Change from baseline to 1 month | 9.6 units on a scale | Standard Deviation 13.3 |
| Botox and DMSO Instillation | Change in Incontinence Quality of Life (I-QoL) Score | Change from baseline to 3 months (n=11, 9) | 8.6 units on a scale | Standard Deviation 14.4 |
| DMSO Instillation | Change in Incontinence Quality of Life (I-QoL) Score | Change from baseline to 1 month | -3.9 units on a scale | Standard Deviation 11.6 |
| DMSO Instillation | Change in Incontinence Quality of Life (I-QoL) Score | Change from baseline to 3 months (n=11, 9) | -4.0 units on a scale | Standard Deviation 9.3 |
Comparison: Change from baseline to 1 month.p-value: 0.024t-test, 2 sided
Comparison: Change from baseline to 3 months.p-value: 0.036t-test, 2 sided
Secondary
Change in Incontinence Impact Questionnaire Short Form (IIQ-7)
The IIQ-7 measures the effect of urinary incontinence on quality of life. It is comprised of 7 items, each with the response scale from 0=Not at all to 3=Greatly. The scores can range from 0 to 21; a low score indicates less impact of incontinence on quality of life.
Time frame: baseline, 1 month, 3 months
Population: Analysis was done according to the principle of intention-to-treat. The sample size was reduced to 9 in the Dimethyl Sulfoxide (DSMO) instillation arm at 3 months due to withdrawal for reasons unrelated to study (cancer).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botox and DMSO Instillation | Change in Incontinence Impact Questionnaire Short Form (IIQ-7) | Change from baseline to 1 month | -2.5 units on a scale | Standard Deviation 4 |
| Botox and DMSO Instillation | Change in Incontinence Impact Questionnaire Short Form (IIQ-7) | Change from baseline to 3 months (n=11, 9) | -1.8 units on a scale | Standard Deviation 4.2 |
| DMSO Instillation | Change in Incontinence Impact Questionnaire Short Form (IIQ-7) | Change from baseline to 1 month | 2.0 units on a scale | Standard Deviation 5.9 |
| DMSO Instillation | Change in Incontinence Impact Questionnaire Short Form (IIQ-7) | Change from baseline to 3 months (n=11, 9) | 1.1 units on a scale | Standard Deviation 3.8 |
Comparison: Change from baseline to 1 month.p-value: 0.051t-test, 2 sided
Comparison: Change from baseline to 3 months.p-value: 0.12t-test, 2 sided
Secondary
Change in International Consultation on Incontinence Questionnaire - Short Form Score (ICIQ-SF)
The ICIQ-SF provides a brief and robust measure to assess the impact of symptoms of incontinence on quality of life and outcome of treatment. The questionnaire has 4 items and the score can range from 0 to 21, with greater values indicating increased severity of symptoms and lower quality of life.
Time frame: baseline, 1 month, 3 months
Population: Analysis was done according to the principle of intention-to-treat. The sample size was reduced to 9 in the DSMO instillation arm at 3 months due to withdrawal for reasons unrelated to study (cancer).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botox and DMSO Instillation | Change in International Consultation on Incontinence Questionnaire - Short Form Score (ICIQ-SF) | Change from baseline to 1 month | -2.4 units on a scale | Standard Deviation 5.8 |
| Botox and DMSO Instillation | Change in International Consultation on Incontinence Questionnaire - Short Form Score (ICIQ-SF) | Change from baseline to 3 months (n=11, 9) | -2.5 units on a scale | Standard Deviation 5.1 |
| DMSO Instillation | Change in International Consultation on Incontinence Questionnaire - Short Form Score (ICIQ-SF) | Change from baseline to 1 month | -0.5 units on a scale | Standard Deviation 4.4 |
| DMSO Instillation | Change in International Consultation on Incontinence Questionnaire - Short Form Score (ICIQ-SF) | Change from baseline to 3 months (n=11, 9) | 0.8 units on a scale | Standard Deviation 4.5 |
Comparison: Change from baseline to 1 month.p-value: 0.42t-test, 2 sided
Comparison: Change from baseline to 3 months.p-value: 0.15t-test, 2 sided
Secondary
Change in Urogenital Distress Inventory (UDI-6)
The UDI-6 measures the effect of urinary incontinence on quality of life. It consists of 6 items, each with the response scale from 0=Not at all to 3=Greatly. The scores can range from 0 to 18; a low score indicates less impact of incontinence on quality of life.
Time frame: baseline, 1 month, 3 months
Population: Analysis was done according to the principle of intention-to-treat. The sample size was reduced to 9 in the DSMO instillation arm at 3 months due to withdrawal for reasons unrelated to study (cancer).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botox and DMSO Instillation | Change in Urogenital Distress Inventory (UDI-6) | Change from baseline to 1 month | -1.9 units on a scale | Standard Deviation 3.7 |
| Botox and DMSO Instillation | Change in Urogenital Distress Inventory (UDI-6) | Change from baseline to 3 months (n=11, 9) | -0.9 units on a scale | Standard Deviation 3.6 |
| DMSO Instillation | Change in Urogenital Distress Inventory (UDI-6) | Change from baseline to 1 month | -0.1 units on a scale | Standard Deviation 1.9 |
| DMSO Instillation | Change in Urogenital Distress Inventory (UDI-6) | Change from baseline to 3 months (n=11, 9) | -0.4 units on a scale | Standard Deviation 3.5 |
Comparison: Change from baseline to 1 monthp-value: 0.18t-test, 2 sided
Comparison: Change from baseline to 3 months.p-value: 0.77t-test, 2 sided
Secondary
Number of Participants With a Decrease in Urinary Urgency at 1 Month and 3 Months
Urinary urgency was measured by the Indevus Urgency Severity Scale (IUSS). The IUSS asks patients to assess the severity of 'urgency' at each void. The scale employs the following wording: Degree of urgency is meant to describe your urge to urinate. Sometimes you may feel a very strong urge to urinate and at other times, you may feel a milder urge prior to the onset of a toilet void. Rate this feeling by circling 0, 1, 2, or 3, defined as: 0: NONE - no urgency, 1: MILD - awareness of urgency, but it is easily tolerated and you can continue with your usual activity or tasks, 2: MODERATE - enough urgency discomfort that it interferes with or shortens your usual activity or tasks, 3: SEVERE - extreme urgency discomfort that abruptly stops all activity or tasks.
Time frame: Baseline, 1 month, 3 months
Population: Analysis was done according to the principle of intention-to-treat. The sample size was reduced to 9 in the DSMO instillation arm at 3 months due to withdrawal for reasons unrelated to study (cancer).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Botox and DMSO Instillation | Number of Participants With a Decrease in Urinary Urgency at 1 Month and 3 Months | 1 month | 4 participants |
| Botox and DMSO Instillation | Number of Participants With a Decrease in Urinary Urgency at 1 Month and 3 Months | 3 months (n=11, 9) | 5 participants |
| DMSO Instillation | Number of Participants With a Decrease in Urinary Urgency at 1 Month and 3 Months | 1 month | 1 participants |
| DMSO Instillation | Number of Participants With a Decrease in Urinary Urgency at 1 Month and 3 Months | 3 months (n=11, 9) | 0 participants |
Comparison: Change between baseline and one monthp-value: 0.31t-test, 2 sided
Comparison: Change between baseline and 3 monthsp-value: 0.038t-test, 2 sided
Secondary
Number of Participants With Decrease in Blaivas-Groutz Anti-Incontinence Score at 1 Month and 3 Months
The Blaivas-Groutz Anti-incontinence scale was used as a measure of urinary incontinence. This scale combines information on the number of incontinent episodes in a 24-hour period, 24-hour pad weights, and a qualitative rating by the patient into a single score ranging from 0 to 6. this score is then used to categorize incontinence as none (0), mild (1-2), moderate (3-4), or severe (5-6).
Time frame: baseline, 1 month, 3 months
Population: Analysis was done according to the principle of intention-to-treat. The sample size was reduced to 9 in the DSMO instillation arm at 3 months due to withdrawal for reasons unrelated to study (cancer).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Botox and DMSO Instillation | Number of Participants With Decrease in Blaivas-Groutz Anti-Incontinence Score at 1 Month and 3 Months | 1 month | 6 participants |
| Botox and DMSO Instillation | Number of Participants With Decrease in Blaivas-Groutz Anti-Incontinence Score at 1 Month and 3 Months | 3 months (n=11, 9) | 6 participants |
| DMSO Instillation | Number of Participants With Decrease in Blaivas-Groutz Anti-Incontinence Score at 1 Month and 3 Months | 1 month | 4 participants |
| DMSO Instillation | Number of Participants With Decrease in Blaivas-Groutz Anti-Incontinence Score at 1 Month and 3 Months | 3 months (n=11, 9) | 2 participants |
Comparison: Change from baseline to one monthp-value: 0.67t-test, 2 sided
Comparison: Change from baseline to 3 months.p-value: 0.2t-test, 2 sided