A Double-Blind, Randomized, Placebo-Controlled Study of Calcium Glycerophosphate Dietary Supplement in Patients with Overactive Bladder Michael J. Kennelly, MD Robbin Clark, RN Marvin S. Medow, PhD McKay Department of Urology Carolinas Medical Center Charlotte, NC

Risk Factors for Urinary Incontinence Predisposing Factors Gender Genetics Race Culture Neurology Anatomy Collagen Status Promoting Factors Bowel Dysfunction Dietary Irritants Activity Level Obesity Menopause Infection Medication Pulmonary Status Psychiatric Status Inciting Factors Childbirth Surgery Pelvic Nerve Damage Radiation

Dietary Irritants Alcoholic beverages Alcoholic beverages Caffeinated products Caffeinated products Citrus juice and fruits Citrus juice and fruits Tomatoes and tomato- based products Tomatoes and tomato- based products Highly spicy foods Highly spicy foods Artificial sweeteners Artificial sweeteners

Purpose To evaluate the efficacy of calcium glycerophospate dietary supplement (Prelief®) in patients with overactive bladder (OAB) To evaluate the efficacy of calcium glycerophospate dietary supplement (Prelief®) in patients with overactive bladder (OAB) To evaluate patient acceptance and satisfaction with Prelief® To evaluate patient acceptance and satisfaction with Prelief®

Study Design Prospective, randomized, single-center, double- blind, placebo-controlled Prospective, randomized, single-center, double- blind, placebo-controlled 3 weeks study duration on Prelief® or placebo 3 weeks study duration on Prelief® or placebo Two study tablets were taken TID daily with meals Two study tablets were taken TID daily with meals Placebo was identical to the active product with respect to size, color, and odor Placebo was identical to the active product with respect to size, color, and odor IRB approved IRB approved

Study Design Double-blind Placebo controlled Single center 60 patients enrolled 4 week study with 3 weeks of treatment on Prelief® or placebo 2 tablets TID with meals Placebo identical to Prelief® in size, shape, color. IRB approved Prelief n=30 Placebo n=30

Inclusion Criteria > 18 years of age with OAB > 18 years of age with OAB OAB defined as: OAB defined as: Urinary Frequency > 8 voids on average/24 hours Urinary Frequency > 8 voids on average/24 hours Urgency Urgency Urge Incontinence > 1 UUI episode/24 hours Urge Incontinence > 1 UUI episode/24 hours confirmed on micturition chart confirmed on micturition chart Stable OAB medications continued throughout the study Stable OAB medications continued throughout the study

Exclusion Criteria Mixed incontinence with 1° symptom is SUI Mixed incontinence with 1° symptom is SUI Acute UTI in run-in period Acute UTI in run-in period Known treatable GU condition Known treatable GU condition UTI, prostatitis, BOO, TCCA, bladder stone, prostate cancer, radiation therapy to pelvis UTI, prostatitis, BOO, TCCA, bladder stone, prostate cancer, radiation therapy to pelvis Uninvestigated hematuria Uninvestigated hematuria Indwelling foley, SPT, or on CIC Indwelling foley, SPT, or on CIC Known allergy or hypersensitivity to Prelief® Known allergy or hypersensitivity to Prelief®

Analysis of Efficacy Data Objective Assessment 3-day voiding diary Mean # voids/24 hr Mean # voids/24 hr Mean # nocturia/24 hr Mean # nocturia/24 hr Mean # incontinent episodes/ 24 hr Mean # incontinent episodes/ 24 hr Mean # of pads used/ 24 hr Mean # of pads used/ 24 hr Subjective Assessment Perception degree of Urgency Incontinence Impact Questionnaire (IIQ) Satisfaction scale Questionnaires

Demographics PlaceboPrelief®p value(n=29) Sex (%) Male7%27% Female92%72%p=0.078 Mean Age (years)6263 Range p=0.99 Race (%) White93%100% Black7%0%p=0.49 On OAB meds (%)31%9% Previous OAB therapy86%54%

Demographics PlaceboPrelief®(n=29) Mean voids/24 hr11.2 (2.84)11.5 (3.49) Mean nocturia/24 hr1.31 (1.69)1.55 (1.06) Mean # incontinent/24 hr2.72 (3.42)3.07 (5.07) Mean # pad/24 hr1.66 (2.62)1.34 (1.20) * all p values > 0.01

Mean Reduction in Frequency and Nocturia at 3 weeks (p=0.65) (p=0.24)

Mean Reduction in Urge Incontinent Episodes and Number of Pads Used (p= 0.41) (p=0.70)

Patient Perception of Urgency at 3 Weeks I was usually not able to hold urine at all I was usually not able to hold urine at all I was usually able to hold urine until I reached a toilet (without leaking) if I went there immediately I was usually able to hold urine until I reached a toilet (without leaking) if I went there immediately I was usually able to finish what I was doing before going to the toilet (without leaking) I was usually able to finish what I was doing before going to the toilet (without leaking)

Patient Satisfaction at 3 weeks How well has this therapy worked for you OAB? How well has this therapy worked for you OAB? Not at all Not at all Poor Poor Fair Fair Good Good Very Good Very Good Excellent Excellent

Patient Satisfaction at 3 Weeks How pleased have you been with this therapy for you OAB? Extremely displeased Extremely displeased Very displeased Very displeased A bit displeased A bit displeased Pleased Pleased Very pleased Very pleased Extremely pleased Extremely pleased

Patient Satisfaction at 3 weeks How much have you benefited from this therapy for your OAB problem? Not at all Not at all A little bit A little bit Some Some A lot A lot

Patient Satisfaction at 3 weeks Mean values for Worked, Pleased, & Benefited Patient Satisfaction at 3 weeks Mean values for Worked, Pleased, & Benefited (p=0.026) (p=0.034) (p=0.0143)

Mean Reduction in IIQ-7 Questions

IIQ-7 Short Form at 3 weeks IIQ-7 Short Form at 3 weeks

IIQ Results at 3 weeks Mean reduction in IIQ-7 Total Score Placebo9.16 Prelief®17.33 Most improvements in Ability to socialize Quantity of sleep Ability to go places Ability to wear clothes Performance of exercises Ability to attend entertainment

Conclusions Prelief® did not show any significant improvements in voiding diary data. Prelief® did not show any significant improvements in voiding diary data. Trend in reduction of urinary frequency & nocturia Trend in reduction of urinary frequency & nocturia Patients noted significant QOL improvements on Prelief® Patients noted significant QOL improvements on Prelief® Workedp= Workedp= Pleasedp=0.034 Pleasedp=0.034 Benefitedp= Benefitedp=0.0143

Conclusions Mechanism by which spicy and acidic foods exacerbate OAB symptoms is unknown Mechanism by which spicy and acidic foods exacerbate OAB symptoms is unknown Theory is sensitization of sensory afferent nerves of urothelium Theory is sensitization of sensory afferent nerves of urothelium Many OAB patients are food sensitive and can identify bladder irritants Many OAB patients are food sensitive and can identify bladder irritants Consequently, if OAB patients are acid food sensitive, Prelief® is safe and efficacious in subjective improvement of symptoms and QOL Consequently, if OAB patients are acid food sensitive, Prelief® is safe and efficacious in subjective improvement of symptoms and QOL

A Double-Blind, Randomized, Placebo-Controlled Study of Calcium Glycerophosphate Dietary Supplement in Patients with Overactive Bladder Realize that many OAB patients are food sensitive and can identify bladder irritants. Realize that many OAB patients are food sensitive and can identify bladder irritants. Council your OAB patients on dietary modification. Council your OAB patients on dietary modification. Understand the mechanism by which spicy and acidic foods exacerbate OAB symptoms is unknown. Understand the mechanism by which spicy and acidic foods exacerbate OAB symptoms is unknown. Theory is sensitization of sensory afferent nerves of urothelium. Theory is sensitization of sensory afferent nerves of urothelium. Do not use calcium glycerophosphate to dramatically change objective voiding diary data (frequency, urgency, or urge incontinence). Do not use calcium glycerophosphate to dramatically change objective voiding diary data (frequency, urgency, or urge incontinence). If OAB patients want a non-Rx alternative to improve subjective symptoms and quality of life, consider calcium glycerophosphate dietary supplement for those OAB patients who are acid food sensitive. If OAB patients want a non-Rx alternative to improve subjective symptoms and quality of life, consider calcium glycerophosphate dietary supplement for those OAB patients who are acid food sensitive.