Behavior and Exercise Versus Drug Treatment in Men With Nocturia (BEDTiMe)

Study Overview
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Brief Summary
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Nocturia, waking at night from sleep to void, is a prevalent and troublesome symptom. Treatment with an alpha-adrenergic antagonist medication (α-blockers) is a standard therapy for LUTS in men, but α-blockers offer only limited reductions in nocturia. While combinations of multiple drugs could be used, many individuals wish to take fewer medications. Participants in the BEDTiMe Nocturia Study will undergo a series of visits during which they will receive a combination of either standard drug therapy (or placebo) and a behavioral intervention tailored to help with nocturia or problems with nocturia. Participants will be evaluated for outcomes at 12 weeks and followed for six months. This study will yield important information related to alternative treatments of nocturia in men, as well as novel information regarding the clinical importance of these nocturia reductions. This study has the potential to alter standards of care.

Detailed Description
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Nocturia, waking at night from sleep to void, is a prevalent and troublesome symptom. While other lower urinary tract symptoms (LUTS)-- including poor urinary stream, urgency, frequency, and straining to void-- are also common, nocturia is one of the most bothersome LUTS. Nocturia causes sleep disruption and is associated with accidental falls and higher utilization of sick days from work. Conditions that result in low volume urinary voids, high urine production at night, and/or primary sleep disturbances will cause nocturia. Overactive bladder (OAB), benign prostatic hyperplasia (BPH), congestive heart failure (CHF), poorly controlled diabetes mellitus (DM), peripheral edema, and obstructive sleep apnea all cause nocturia. Individual patients frequently have multiple conditions potentially related to nocturia, which highlights the need for strategies that are broad-based interventions. Treatment with an alpha-adrenergic antagonist medication (α-blockers) is a standard therapy for LUTS in men, but α-blockers offer only limited reductions in nocturia. While combinations of multiple drugs could also be employed to more successfully treat nocturia, non-drug treatments are an important option for those unwilling or unable to take additional medications. The BEDTiMe Nocturia Study (Behavior and Exercise or Drug Trial in Men with Nocturia), is a two-site (Atlanta and Birmingham), randomized, clinical trial. The 200 male participants will be stratified by degree of nocturia and urinary flow rate and randomized to three treatment arms: 1) α-blocker therapy alone; versus 2) a standardized, multicomponent behavioral and exercise therapy (M-BET), given with placebo tablets; versus 3) combination therapy (M-BET and α-blockers). The M-BET intervention includes: training in pelvic floor muscle rehabilitation, self monitoring with bladder diaries, and teaching urge suppression and other skills to inhibit detrusor contractions; fluid management strategies; sleep hygiene strategies; and non-pharmacological management of lower extremity edema. Interventions similar to M-BET have shown reductions in nocturia in women with urge urinary incontinence (UI) that exceeded benefit from anticholinergic drug therapy. The use of this intervention in men builds upon strong pilot data from the MINIM trial (Multicomponent Interventions for Nocturia in Men; VA GRECC Pilot, VA Medical Research Services) and the ongoing study Behavioral Treatment For Overactive Bladder In Men (VA RR&D B02-2489R, Burgio, PI). The study design allows 3 main research questions to be addressed: 1) Does M-BET reduce nocturia more than α-blockers?; 2) Does M-BET improve sleep more than α-blockers?; and 3) Will combination therapy be more effective than either treatment alone? The main outcomes will be nocturia reduction and sleep improvement at 12 weeks. Nocturia reduction will be assessed by participant completed bladder diaries and sleep improvement will be assessed by wrist-actigraph determined sleep efficiency, total sleep time, and wake time after sleep onset. This study will yield important information related to alternative treatments of nocturia in male veterans, as well as novel information regarding the clinical importance of these nocturia reductions. Though many clinicians employ single-agent α-blockers routinely for the treatment of nocturia, few utilize multicomponent behavioral interventions or use behavioral therapy. Thus, this study has the potential to alter standards of care.

Official Title
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Behavior and Exercise Versus Drug Treatment in Men With Nocturia

Conditions
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Nocturia

Intervention / Treatment
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* Behavioral: Behavioral
* Drug: tamsulosin (alpha-adrenergic antagonist medication)
* Drug: placebo
* Behavioral: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Nocturia ≥2 episodes / night average on the screening diary; Willingness and appropriateness to receive an α- blocker; Willingness to keep a bladder and sleep diary; Willingness to wear a wrist actigraph; and Willingness to make study visits Exclusion Criteria: Evidence of overt bladder outlet obstruction: peak uroflow <4 mL/sec on a void of ≥125 mL, or a PVR of ≥ 300 mL; Use of clean intermittent self-catheterization at home or having been instructed by a provider to do so within the last 12 months; Genitourinary cancer, including active prostate cancer with ongoing surgical or radiation treatment, or the need of treatment, or bladder cancer, or persistent unexplained hematuria; Obstructive sleep apnea with CPAP use, provider diagnosis with symptoms, or strong suspicion of diagnosis during screening; Having Parkinson's disease with an uncontrolled tremor (invalidates wrist actigraphy); Poorly controlled congestive heart failure as evidenced on physical examination; Poorly controlled diabetes mellitus with either hemoglobin A1c of ≥ 7.5 or a random glucose ≥ 200 within last 3 months; or Unstable health conditions expected to result in death or hospitalization within 3 months, as assessed by PI or Site PI; Previously receiving intensive bladder training; Allergic to Tamsulosin; Previous spinal cord injury; Currently on dialysis or in consideration for dialysis due to end stage renal disease; More than 2 urinary tract infections within the last 12 months; Not able to transfer independently from a wheelchair to the toilet; Unstable dose of diuretic within the past 3 months; Has an artificial urinary sphincter; Impaired mental status; TURP or other urologic surgery within the last 6 months.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: Factorial design with no true placebo arm- drug alone versus behavior alone versus drug + behavior
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Behavioral and Exercise Therapy (M-BET)<br>Multicomponent behavior and exercise therapy program (M-BET) - pelvic floor muscle exercises, urge suppression strategies, fluid strategies, sleep hygiene & non-pharmacological management of peripheral edema. M-BET alone will be given with placebo capsules. | Behavioral: Behavioral<br>* Multicomponent Behavioral and Exercise Therapy (M-BET) - pelvic floor muscle exercises, urge suppression strategies, fluid strategies, sleep hygiene & non-pharmacological management of peripheral edema.<br>* Other names: M-BET;Drug: placebo<br>* tamsulosin placebo<br>|
| Active Comparator: Drug Therapy w/ Behavioral Placebo<br>alpha-adrenergic antagonist medication with a placebo behavioral intervention | Drug: tamsulosin (alpha-adrenergic antagonist medication)<br>* 0.4 mg given daily<br>* Other names: Drug Group;Behavioral: placebo<br>* placebo behavioral intervention<br>* Other names: Face Recognition Behavioral placebo;|
| Active Comparator: Combination Therapy<br>Combination therapy: MBET and alpha-adrenergic antagonist medication | Behavioral: Behavioral<br>* Multicomponent Behavioral and Exercise Therapy (M-BET) - pelvic floor muscle exercises, urge suppression strategies, fluid strategies, sleep hygiene & non-pharmacological management of peripheral edema.<br>* Other names: M-BET;Drug: tamsulosin (alpha-adrenergic antagonist medication)<br>* 0.4 mg given daily<br>* Other names: Drug Group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nocturia episodes (voiding diary) | Participant recorded bladder diary over 7-day that included nocturia episodes | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep quality | Pittsburgh Sleep Quality Index | 12 weeks | 
| Bother from nocturia | American Urological Association 7 symptom index accompanying bother index; specific question on nocturia | 12 weeks | 
| Symptom-specific quality of life measure | The International Consultation on Incontinence Nocturia Quality of Life Instrument (ICI-NQOL) | 12 weeks | 
| Nocturia episodes (self report) | The 7th question on the American Urological Association 7 Symptom Index: Over the past month, how many times did you most typically get up to urinate from the time that you went to bed at night until the time you got up in the morning? 0, 1, 2, 3, 4 or 5 or more. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sleep, Quality of life, nocturia