A Double-Blind, Randomized, A Double-Blind, Randomized, Placebo-Controlled Study of Placebo-Controlled Study of Calcium Glycerophosphate Calcium Glycerophosphate

Dietary Supplement in Dietary Supplement in Patients with Overactive Patients with Overactive

BladderBladderMichael J. Kennelly, MDMichael J. Kennelly, MDRobbin Clark, RNRobbin Clark, RN

Marvin S. Medow, PhDMarvin S. Medow, PhDMcKay Department of UrologyMcKay Department of Urology

Carolinas Medical CenterCarolinas Medical CenterCharlotte, NCCharlotte, NC

Risk Factors for Urinary Risk Factors for Urinary IncontinenceIncontinence

Predisposing FactorsGender

GeneticsRace

CultureNeurologyAnatomy

Collagen Status

Promoting FactorsBowel DysfunctionDietary Irritants

Activity LevelObesity

MenopauseInfection

MedicationPulmonary StatusPsychiatric Status

Inciting FactorsChildbirthSurgery

Pelvic Nerve DamageRadiation

Dietary IrritantsDietary Irritants

Alcoholic beveragesAlcoholic beverages Caffeinated Caffeinated

productsproducts Citrus juice and Citrus juice and

fruitsfruits Tomatoes and Tomatoes and

tomato-based tomato-based productsproducts

Highly spicy foodsHighly spicy foods Artificial sweetenersArtificial sweeteners

PurposePurpose

To evaluate the efficacy of calcium To evaluate the efficacy of calcium glycerophospate dietary supplement glycerophospate dietary supplement (Prelief®) in patients with (Prelief®) in patients with overactive bladder (OAB)overactive bladder (OAB)

To evaluate patient acceptance and To evaluate patient acceptance and satisfaction with Prelief®satisfaction with Prelief®

Study DesignStudy Design

Prospective, randomized, single-center, Prospective, randomized, single-center, double-blind, placebo-controlleddouble-blind, placebo-controlled

3 weeks study duration on Prelief® or 3 weeks study duration on Prelief® or placeboplacebo

Two study tablets were taken TID daily Two study tablets were taken TID daily with mealswith meals

Placebo was identical to the active product Placebo was identical to the active product with respect to size, color, and odorwith respect to size, color, and odor

IRB approvedIRB approved

Inclusion CriteriaInclusion 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 Urinary Frequency > 8 voids on average/24 hourshours

UrgencyUrgency Urge Incontinence > 1 UUI episode/24 Urge Incontinence > 1 UUI episode/24

hours hours confirmed on micturition chartconfirmed on micturition chart

Stable OAB medications continued Stable OAB medications continued throughout the studythroughout the study

Exclusion CriteriaExclusion Criteria

Mixed incontinence with 1° symptom is SUIMixed incontinence with 1° symptom is SUI Acute UTI in run-in periodAcute UTI in run-in period Known treatable GU conditionKnown treatable GU condition

UTI, prostatitis, BOO, TCCA, bladder stone, UTI, prostatitis, BOO, TCCA, bladder stone, prostate cancer, radiation therapy to pelvisprostate cancer, radiation therapy to pelvis

Uninvestigated hematuriaUninvestigated hematuria Indwelling foley, SPT, or on CICIndwelling foley, SPT, or on CIC Known allergy or hypersensitivity to Known allergy or hypersensitivity to

Prelief®Prelief®

Analysis of Efficacy DataAnalysis of Efficacy Data

Objective Objective AssessmentAssessment

3-day voiding diary3-day voiding diary Mean # voids/24 hrMean # voids/24 hr Mean # nocturia/24 Mean # nocturia/24

hrhr Mean # incontinent Mean # incontinent

episodes/ 24 hrepisodes/ 24 hr Mean # of pads Mean # of pads

used/ 24 hrused/ 24 hr

Subjective Subjective AssessmentAssessment

Perception degree Perception degree of Urgencyof Urgency

Incontinence Incontinence Impact Impact Questionnaire (IIQ)Questionnaire (IIQ)

Satisfaction scale Satisfaction scale QuestionnairesQuestionnaires

DemographicsDemographics

Placebo Prelief® p value

(n=29) (n=29)Sex (%) Male 7% 27% Female 92% 72%p=0.078Mean Age (years) 62 63 Range 28-86 30-85

p=0.99Race (%) White 93% 100% Black 7% 0%p=0.49On OAB meds (%) 31% 9%Previous OAB therapy 86% 54%

DemographicsDemographics

Placebo Prelief®(n=29) (n=29)

Mean voids/24 hr 11.2 (2.84) 11.5 (3.49)

Mean nocturia/24 hr 1.31 (1.69) 1.55 (1.06)

Mean # incontinent/24 hr 2.72 (3.42) 3.07 (5.07)

Mean # pad/24 hr 1.66 (2.62) 1.34 (1.20)

* all p values > 0.01

Mean Reduction in Mean Reduction in Frequency and Nocturia at Frequency and Nocturia at

3 weeks 3 weeks

0

0.1

0.2

0.3

0.4

0.5

0.6

Frequency Nocturia

PlaceboPrelief

(p=0.65) (p=0.24)

Mean Reduction in Urge Mean Reduction in Urge Incontinent Episodes and Incontinent Episodes and

Number of Pads UsedNumber of Pads Used

0

0.2

0.4

0.6

0.8

1

1.2

Urge Incontinence # Pads Used

PlaceboPrelief

(p= 0.41) (p=0.70)

Patient Perception of Urgency Patient Perception of Urgency at 3 Weeksat 3 Weeks

I was usually not able I was usually not able to hold urine at allto hold urine at all

I was usually able to I was usually able to hold urine until I hold urine until I reached a toilet reached a toilet (without leaking) if I (without leaking) if I went there went there immediatelyimmediately

I was usually able to I was usually able to finish what I was finish what I was doing before going to doing before going to the toilet (without the toilet (without leaking)leaking)

0%

5%

10%

15%

20%

25%

30%

35%

40%

Improvement

PlaceboPrelief

Patient Satisfaction at 3 Patient Satisfaction at 3 weeksweeks

How well has this How well has this therapy therapy workedworked for you OAB?for you OAB?

Not at allNot at all PoorPoor FairFair GoodGood Very GoodVery Good ExcellentExcellent

0%5%

10%15%20%25%30%35%40%45%

Not at

All

Poor

Fair

Good

Very Goo

d

Placebo Prelief

Patient Satisfaction at 3 Patient Satisfaction at 3 WeeksWeeks

How How pleasedpleased have have you been with this you been with this therapy for you therapy for you OAB?OAB?

Extremely displeasedExtremely displeased Very displeasedVery displeased A bit displeasedA bit displeased PleasedPleased Very pleasedVery pleased Extremely pleasedExtremely pleased

0%5%

10%15%20%25%30%35%40%45%50%

Ex. DP

Very DP

Bit DP

PleasedVery P

Placebo Prelief

Patient Satisfaction at 3 Patient Satisfaction at 3 weeksweeks

How much have How much have you you benefitedbenefited from this therapy from this therapy for your OAB for your OAB problem?problem?

Not at allNot at all A little bitA little bit SomeSome A lotA lot

0%

10%

20%

30%

40%

50%

60%

Not atAll

A littleBit

Some A Lot

Placebo Prelief

Patient Satisfaction at 3 Patient Satisfaction at 3 weeksweeks

Mean values for Worked, Pleased, & Mean values for Worked, Pleased, & BenefitedBenefited

0

0.5

1

1.5

2

2.5

3

3.5

4

Worked Pleased Benefited

PlaceboPrelief

(p=0.026) (p=0.034) (p=0.0143)

IIQ Results at 3 weeksIIQ Results at 3 weeks Mean reduction in IIQ-7 Mean reduction in IIQ-7

Total Score Total Score PlaceboPlacebo 9.169.16 Prelief®Prelief®

17.3317.33

Most improvements in Most improvements in Ability to socializeAbility to socialize Quantity of sleepQuantity of sleep Ability to go placesAbility to go places Ability to wear clothesAbility to wear clothes Performance of exercisesPerformance of exercises Ability to attend Ability to attend

entertainmententertainment

0%

10%

20%

30%

40%50%

60%

70%

80%

90%

Improve Same Worse

Placebo Prelief

ConclusionsConclusions

Prelief® did not show any significant Prelief® did not show any significant improvements in voiding diary data.improvements in voiding diary data. Trend in reduction of urinary frequency Trend in reduction of urinary frequency

& nocturia& nocturia

Patients noted significant QOL Patients noted significant QOL improvements on Prelief®improvements on Prelief® WorkedWorked p= 0.026p= 0.026 PleasedPleased p=0.034p=0.034 BenefitedBenefited p=0.0143p=0.0143

ConclusionsConclusions Mechanism by which spicy and acidic Mechanism by which spicy and acidic

foods exacerbate OAB symptoms is foods exacerbate OAB symptoms is unknownunknown Theory is sensitization of sensory afferent Theory is sensitization of sensory afferent

nerves of urotheliumnerves of urothelium Many OAB patients are food sensitive Many OAB patients are food sensitive

and can identify bladder irritantsand can identify bladder irritants Consequently, if OAB patients are acid Consequently, if OAB patients are acid

food sensitive, Prelief® is safe and food sensitive, Prelief® is safe and efficacious in subjective improvement of efficacious in subjective improvement of symptoms and QOLsymptoms and QOL

A Double-Blind, Randomized, Placebo-A Double-Blind, Randomized, Placebo-Controlled Study of Calcium Glycerophosphate Controlled Study of Calcium Glycerophosphate

Dietary Supplement in Patients with Dietary Supplement in Patients with Overactive BladderOveractive Bladder

Realize that many OAB patients are food sensitive and Realize that many OAB patients are food sensitive and can identify bladder irritants.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 Understand the mechanism by which spicy and acidic

foods exacerbate OAB symptoms is unknown. foods exacerbate OAB symptoms is unknown. Theory is sensitization of sensory afferent nerves of Theory is sensitization of sensory afferent nerves of

urothelium.urothelium. Do not use calcium glycerophosphate to dramatically Do not use calcium glycerophosphate to dramatically

change objective voiding diary data (frequency, change objective voiding diary data (frequency, urgency, or urge incontinence).urgency, or urge incontinence).

If OAB patients want a non-Rx alternative to improve If OAB patients want a non-Rx alternative to improve subjective symptoms and quality of life, consider subjective symptoms and quality of life, consider calcium glycerophosphate dietary supplement for calcium glycerophosphate dietary supplement for those OAB patients who are acid food sensitive.those OAB patients who are acid food sensitive.