Effect of Beta-alanine and Pelvic Floor Muscle Training on Urinary Incontinence After Radical Prostatectomy (BELA)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness of beta-alanine in combination with pelvic floor muscle training (PFMT) compared to PFMT plus placebo in men undergoing radical prostatectomy.

Detailed Description
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This study will assess efficacy of beta-alanine in combination with PFMT for the treatment of participants with urinary incontinence after radical prostatectomy. B-alanine is a component of L-carnosine (with L-histidine), which is needed for its synthesis. Βeta-alanine, thanks to its bioavailability) is a commonly used supplement that can improve exercise performance by increasing the amount of carnosine in striated muscle tissues. Supplementation of beta-alanine in elderly patients has resulted in an increase in physical activity, less fatigue and overall increase in L-carnosine concentration in muscles. PFMT utilization is considered a strong predictor of early return of urinary continence after radical prostatectomy (RP). We hypothesize, that combination of PFMT with beta-alanine could result in improved urinary continence after RP. The intervention will start 30 days before the surgery and will continue until primary outcome is met. Beta-alanine/placebo will be given daily. Efficacy, pharmacokinetics, biomarkers, tissue histology, participants reported outcomes and safety will be assessed. The total duration of study will be approximately 6 months.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effect of Beta-alanine and Pelvic Floor Muscle Training on Urinary Incontinence After Radical Prostatectomy (BELA)

Conditions
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Prostate Cancer, Urinary Incontinence, Beta-Alanine, Pelvic Floor Muscle Training, Radical Prostatectomy

Intervention / Treatment
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* Drug: Beta-Alanine
* Drug: Placebo
* Procedure: Pelvic floor muscle training (PFMT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 40-80 years Able to give informed consent Histologically proven prostate cancer BMI <35 No other cancer treatment Continent Good physical and mental activity On normal diet Scheduled for radical prostatectomy (open or robotic) Exclusion Criteria: Other malignant cancer (except for benign skin cancer) Age > 80 years Diabetes mellitus (any type) Chronic bowel inflammatory disease Urinary incontinence Impaired mental activity Previous radiotherapy of hormonal therapy Vegetarian/vegan/on macrobiotic diet

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Beta-alanine + PFMT<br>Participants will ingest an active supplement containing beta-alanine for a period of maximum 6 months. During the whole period, participants will take part in a structured program of PMFT. After first month, the participants will undergo radical prostatectomy. | Drug: Beta-Alanine<br>* Participants will receive 1150mg of beta-alanine three times a day<br>* Other names: Intervention group;Procedure: Pelvic floor muscle training (PFMT)<br>* Participants in both groups will undergo PFMT training program<br>|
| Experimental: Placebo + PFMT<br>Participants will ingest a placebo supplement containing no beta-alanine for a period of maximum 6 months. During the whole period, participants will take part in a structured program of PMFT. After first month, the participants will undergo radical prostatectomy. | Drug: Placebo<br>* Participants will receive matching placebo three times a day<br>* Other names: Control group;Procedure: Pelvic floor muscle training (PFMT)<br>* Participants in both groups will undergo PFMT training program<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Continence (days) | Continence is defined by number of pads used and measured by one hour pad test. Number of pads use will be determined according to EPIC-SF questionnaire | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of physical activity of participants | To assess physical activity of the participants using Physical activity level (PAL), the number of participants having recommended PAL (PAL 1.75: a weekly average PAL of ≥1.75) < 1.4 = extremely inactive, > 2.4 = extremely active | up to 6 months | 
| Number of participants with laboratory abnormalities as measure of safety | Number of participants with laboratory abnormalities (hematology, serum chemistry and liver function test) will be determined | up to 6 months | 
| Number of participants with adverse events | Incidence of adverse events in the combined beta-alanine and PFMT compared to PFMT and placebo treatment. Surgical complications will be evaluated according to Clavien-Dindo classification | up to 6 months | 
| Assessment of quality of life (QoL) change in both groups of participants | During the study period, participants will be asked to fill in clinical validated EuroQuol-5dimensions-5levels (EQ-5D-5L) questionnaire 0 = the worst to 100 = the best QoL outcome | up to 6 months | 
| Muscle carnosine concentration | Integrity and architecture of muscle tissue will be assessed in 4 µm thick sections of formalin-fixed, paraffin-embedded, hematoxylin-eosin stained tissue samples. | at week 4 (surgery) |