None listed
Conditions
Brief summary
Overactive bladder (OAB) is a common problem in the elderly and undertreatment is a concern due to the perception by clinicians with regard to side-effects. Amongst Geriatricians the cognitive side-effects are of particular concern and these drugs are relatively contraindicated in cognitive impairment. Treatment is often tailored to individual needs and comorbidities and there is no standard treatment for overactive bladder for this cohort. Where the drug is clinically indicated, there is anecdotal evidence that Geriatricians will prescribe solifenacin rather than oxybutynin due to theoretically less impact on cognitive function. Unfortunately trial evidence examining the cognitive impact of these drugs is lacking. This investigator initiated pilot study is designed to explore the cognitive effects of two different treatment licensed treatments for OAB, namely solifenacin and oxybutynin patch. Efficacy and tolerability will be assessed as secondary outcomes. The oxybutynin patch has been chosen over oral oxybutynin as the frequency of side-effects is recognised to be lower. There is no placebo as such, but cognition and bladder function will be assessed following significant washout periods during the study. A cross-over design has been chosen over a parallel group study for this pilot study as the numbers for a parallel group study would be prohibitively large and our design allows good within subject comparisons of cognition. It is reasonable to conduct this pilot as currently there is only one cognitive study looking at single doses of solifenacin in healthy elderly people, which showed solifenacin was not associated with cognitive impairment. We speculate that solifenacin will have less effect on cognition than oxybutynin patch with repeat dosing in healthy elderly female volunteers. The proposed dose of solifenacin used is based on available clinical data that shows most of the dose-response is achieved at 5mg while the use of 10mg dose is more likely associated with adverse effect . There is minimal additional clinical benefit from 10mg compared to 5mg. The use of 3.9mg transdermal patch is supported by a placebo, controlled dose escalation trial. Subjects will be recruited from the Women’s Health Centre outpatient clinic at the RAH or through advertisement. To participate in this trial, all subjects will meet criteria for treatment with these agents. They will be female, age 60 or above with overactive bladder syndrome who have not been on treatment or been off treatment for one month. There will be periods with no treatment during the initial run-in and between treatments in order to establish baseline bladder and cognitive function - this will be discussed with patients prior to commencing the clinical trial. The subjects will have the opportunity to try two different treatment for OAB. Possible risks that can occur in subjects include the following: Study drugs: Adverse effects listed in product information for solifenacin and oxybutynin Blood sampling: Discomfort, bruising or infection on the venipuncture site Cognitive testing: Mental fatigue and potential distress
Interventions
Arm 1 solifenacin oral 5 mg tablet daily will be dispensed at Royal Adelaide Hospital Pharmacy. Treatment will continue for 4 weeks followed by a washout period of 3 weeks with no active treatment. Subjects on solifenacin will crossover to receive oxybutynin patch for 4 weeks.
Arm 2 oxybutynin 3.9mg patch changed every 2 days, will be dispensed at Royal Adelaide Hospital Pharmacy. Transdermal patch will be applied to the skin, such as abdomen, buttocks or hip. Treatment will continue for 4 week
Arm 1 solifenacin oral 5 mg tablet daily will be dispensed at Royal Adelaide Hospital Pharmacy. Treatment will continue for 4 weeks followed by a washout period of 3 weeks with no active treatment. Subjects on solifenacin will crossover to receive oxybutynin patch for 4 weeks. Arm 2 oxybutynin 3.9mg patch changed every 2 days, will be dispensed at Royal Adelaide Hospital Pharmacy. Transdermal patch will be applied to the skin, such as abdomen, buttocks or hip. Treatment will continue for 4 weeks followed by a washout period of 3 weeks with no active treatment. Subjects on oxybutynin patch will crossover to receive solifenacin for 4 weeks.
Sponsors
Bianca Wong
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Age 60 or above Female Mini Mental State Examination score greater than 24 Body mass index 22-35 Established diagnosis of overactive bladder as defined by the International Continence Society Able to complete cognitive testing at screening visit Able to give consent English speaking
Exclusion criteria
Moderate or severe cognitive impairment (Mini Mental State Examination less than or equal to 24 at screening). Calculated creatinine clearance of less than 30ml/min via Cockcroft-Gault equation Clinically significant hepatic impairment in the opinion of the investigator Subjects on treatment with a potent CYP3A4 inhibitor, e.g. ketoconazole, protease inhibitors, macrolides, moxifloxacin, ritonavir, nelfinavir, itraconazole, cyclosporin, macrolide.8 Depression as determined by the Geriatric Depression Scale (GDS) short form more than or equal to 5 at screening. History of urinary retention, severe gastrointestinal obstruction (including paralytic ileus or intestinal atony or toxic megacolon or severe ulcerative colitis), myasthenia gravis, uncontrolled narrow angle glaucoma or shallow anterior chamber or deemed to be at risk for these conditions. Unplanned hospitalization within the last 4 weeks prior to participation of the study Severe pelvic organ prolapse or vaginitis. Genitourinary surgery within the last 6 months. Post void residual urine volume equal to or greater than 150ml (bladder ultrasound) at screening. Severe cardiovascular disease Bladder tumour or stone Uncontrolled diabetes mellitus with HbA1c greater than 9% Known hepatitis B, hepatitis C or HIV at time of screening History of drug and / or alcohol abuse at time of screening An average weekly alcohol intake of greater than 14 units within 3 months prior to screening History of known or suspected hypersensitivity to solifenacin succinate, oxybutynin hydrochloride, other anti-cholinergics or lactose, to any component of the dosage form Currently on drug therapy for overactive bladder symptoms or has history of non-drug treatment intended to treat overactive bladder symptoms within 1 month prior to screening Currently on acetylcholinesterase inhibitor (e.g. donepezil) or tricyclic antidepressant Unstable doses of prescribed medication within 1 month prior to screening, which in the opinion of the Investigator, will interfere with the study procedures or compromise safety Any clinically significant abnormality following Investigator review of the physical examination or ECG Any clinically significant abnormal heart rate or blood pressure measurements, at the screening visit (dBP greater than 100mmHg, sBP greater than 180mmHg or sBP less than 100mmHg or HR less than 40bpm or greater than 100bpm) Any clinically significant abnormality following Investigator review of the biochemistry & haematology results which, in the opinion of the Investigator, contraindicates their participation Participated in any clinical study within the last 30 days prior to screening Has had full neuropsychological testing in the last 12 months Any skin condition assessed by the Investigator which would preclude the use of a transdermal patch Any other clinical condition or diagnosis as assessed by the Investigator would otherwise consider as a contraindication for participation in the study
Outcome results
None listed