Overactive Bladder
Conditions
Keywords
Administration, Intravesical, Anesthetics, Local
Brief summary
The purpose of this study is to determine whether alkalized lidocaine instilled into the bladder is effective in the treatment of overactive bladder (OAB).
Detailed description
Existing first-line treatments for overactive bladder are limited by requirements for chronic dosing and associated systemic side effects. Small case series suggest that bladder instillation of lidocaine may be effective in downregulating the afferent neuronal activity of a sensitized bladder, leading to elevation of the urge sensory threshold and decreasing detrusor activity. However, neither the effectiveness over placebo nor the durability of the response has been previously investigated. Comparison(s): We propose a randomized, prospective double-blinded controlled trial to determine if a three-week trial of intravesical alkalized lidocaine instillation decreases symptoms of overactive bladder more than instillation of normal saline using a validated outcome instrument, the OAB-q.
Interventions
DRUGalkalinized xylocaine
30 cc of 1% xylocaine and 10 cc of 0.9% sodium bicarbonate, dosed twice a week for three weeks
DRUGplacebo
normal saline
Sponsors
Berlex Foundation
Frank Tu
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Female patient, 18 years of age and older * Overactive bladder defined as: * Urinary frequency defined as eight or more voids in a 24 hour period \> 50% of days of the week * Symptoms of urgency * Symptoms of at least three months duration
Exclusion criteria
* Positive urine culture in the past month, or more than 3 episodes of bladder infection in the last 2 months * Stress or overflow urinary incontinence (determined by clinician) if more than 14 episodes of urinary incontinence per week; also insensate incontinence * Pregnancy * Seizure disorder or clinically significant renal disease, allergy to lidocaine, uninvestigated hematuria, or history of urinary/reproductive tract malignancy * Post-void residual more than 200 cc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Median Number of Daily Voiding Episodes (by 3-day Voiding Diary) at Six Weeks. | 6 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SF-12 Physical at 6 Weeks | 6 weeks | SF-12 physical is an abbreviated version of the SF-36 a widely used, general health care quality of life instrument. Scores range from 0-100, and higher scores are better outcomes. |
| OAB-q (Symptom Scale) at 6 Weeks | 6 weeks | OAB-q SS is a 7 item overactive bladder symptom bother sub scale, ranging from 0-100, higher scores mean worse outcome for bother |
| Median Number of Daily Voiding Episodes at 12 Months. | 12 months | — |
| Average Weekly NRS for Frequency at 6 Weeks | 6 weeks | NRS - numerical rating scale, 0-10 is the range, and higher scores are worse frequency |
| Cystometric Assessment of Maximal Bladder Capacity at 6 Weeks Only. | 6 weeks | This is based on retrograde infusion of sterile water into the bladder using a catheter, the maximum tolerated volume serving to define how much distension a woman can tolerate. |
| Global Assessment of Change - Frequency at 6 Weeks | 6 weeks | This is patient overall assessment of change in overactive bladder symptoms after treatment. 0% is no change, 100% is total resolution of symptoms |
Countries
United States
Participant flow
Recruitment details
Two medical clinic sites were used between January 2007 and March 2011, initially the Evanston Continence Center (Evanston, IL), and subsequently to augment recruitment, North Shore Urogynecology (Lake Forest, IL, added July 2009).
Pre-assignment details
no wash out, no run-in
Participants by arm
| Arm | Count |
|---|---|
| 1/Active alkalinized xylocaine: 30 cc of 1% xylocaine and 10 cc of 0.9% sodium bicarbonate | 12 |
| 2/Placebo normal saline | 10 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 2 |
Baseline characteristics
| Characteristic | 2/Placebo | Total | 1/Active |
|---|---|---|---|
| Age, Continuous | 54.3 years STANDARD_DEVIATION 18.3 | 51.9 years STANDARD_DEVIATION 14 | 50.4 years STANDARD_DEVIATION 11.3 |
| length of OAB symptoms | 7.7 years STANDARD_DEVIATION 5.4 | 7.2 years STANDARD_DEVIATION 8.5 | 6.8 years STANDARD_DEVIATION 10.2 |
| prior anticholinergic use | 5 Participants | 13 Participants | 8 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 | 2 Participants | 2 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 7 Participants | 15 Participants | 8 Participants |
| Region of Enrollment United States | 10 participants | 22 participants | 12 participants |
| Sex: Female, Male Female | 10 Participants | 22 Participants | 12 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 7 |
| other Total, other adverse events | 3 / 11 | 2 / 7 |
| serious Total, serious adverse events | 0 / 11 | 0 / 7 |
Outcome results
Primary
Median Number of Daily Voiding Episodes (by 3-day Voiding Diary) at Six Weeks.
Time frame: 6 weeks
Population: only 16 participants completed this diary
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1/Active | Median Number of Daily Voiding Episodes (by 3-day Voiding Diary) at Six Weeks. | 9.5 voids/day |
| 2/Placebo | Median Number of Daily Voiding Episodes (by 3-day Voiding Diary) at Six Weeks. | 9 voids/day |
Comparison: null hypothesis - no difference in average number of voids between the 2 groups, power calculation estimated 40 participants needed per arm to show a 2 void difference between lidocaine and saline placebo.p-value: 0.588Kruskal-Wallis
Secondary
Average Weekly NRS for Frequency at 6 Weeks
NRS - numerical rating scale, 0-10 is the range, and higher scores are worse frequency
Time frame: 6 weeks
Population: Not all women completed this measure
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1/Active | Average Weekly NRS for Frequency at 6 Weeks | 4 score on a 0-10 scale |
| 2/Placebo | Average Weekly NRS for Frequency at 6 Weeks | 4 score on a 0-10 scale |
p-value: 0.802Kruskal-Wallis
Secondary
Cystometric Assessment of Maximal Bladder Capacity at 6 Weeks Only.
This is based on retrograde infusion of sterile water into the bladder using a catheter, the maximum tolerated volume serving to define how much distension a woman can tolerate.
Time frame: 6 weeks
Population: Not all women were able to return for cystometry
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1/Active | Cystometric Assessment of Maximal Bladder Capacity at 6 Weeks Only. | 316 mL |
| 2/Placebo | Cystometric Assessment of Maximal Bladder Capacity at 6 Weeks Only. | 275 mL |
p-value: 0.366Kruskal-Wallis
Secondary
Global Assessment of Change - Frequency at 6 Weeks
This is patient overall assessment of change in overactive bladder symptoms after treatment. 0% is no change, 100% is total resolution of symptoms
Time frame: 6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1/Active | Global Assessment of Change - Frequency at 6 Weeks | 40 percent improvement |
| 2/Placebo | Global Assessment of Change - Frequency at 6 Weeks | 10 percent improvement |
p-value: 0.342Kruskal-Wallis
Secondary
Median Number of Daily Voiding Episodes at 12 Months.
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1/Active | Median Number of Daily Voiding Episodes at 12 Months. | 7 voids/day |
| 2/Placebo | Median Number of Daily Voiding Episodes at 12 Months. | 8 voids/day |
p-value: 0.617Kruskal-Wallis
Secondary
OAB-q (Symptom Scale) at 6 Weeks
OAB-q SS is a 7 item overactive bladder symptom bother sub scale, ranging from 0-100, higher scores mean worse outcome for bother
Time frame: 6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1/Active | OAB-q (Symptom Scale) at 6 Weeks | 15 score on a scale |
| 2/Placebo | OAB-q (Symptom Scale) at 6 Weeks | 28 score on a scale |
p-value: 0.189Kruskal-Wallis
Secondary
SF-12 Physical at 6 Weeks
SF-12 physical is an abbreviated version of the SF-36 a widely used, general health care quality of life instrument. Scores range from 0-100, and higher scores are better outcomes.
Time frame: 6 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 1/Active | SF-12 Physical at 6 Weeks | 49 score on scale |
| 2/Placebo | SF-12 Physical at 6 Weeks | 56 score on scale |
p-value: 0.441Kruskal-Wallis