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

Phase 4

Completed

• Conditions: Nocturia
• Interventions: Behavioral: Behavioral; Drug: tamsulosin (alpha-adrenergic antagonist medication); Behavioral: placebo

• Registration Number: NCT00824200
• Lead Sponsor: Atlanta VA Medical Center

Brief Summary

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

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.

Study Timeline

• Study Start: 2008-07
• Study First Submitted: 2009-01-15
• Study First Submitted QC: 2009-01-15
• Study First Posted: 2009-01-16
• Primary Completion: 2014-02
• Study Completion: 2014-03
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-09
• Last Update Posted: 2021-09-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 72

Inclusion Criteria

1. Nocturia ≥2 episodes / night average on the screening diary;
2. Willingness and appropriateness to receive an α- blocker;
3. Willingness to keep a bladder and sleep diary;
4. Willingness to wear a wrist actigraph; and
5. Willingness to make study visits

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Behavioral and Exercise Therapy (M-BET)	Behavioral	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 and Exercise Therapy (M-BET)	placebo	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.
Drug Therapy w/ Behavioral Placebo	tamsulosin (alpha-adrenergic antagonist medication)	alpha-adrenergic antagonist medication with a placebo behavioral intervention
Drug Therapy w/ Behavioral Placebo	placebo	alpha-adrenergic antagonist medication with a placebo behavioral intervention
Combination Therapy	Behavioral	Combination therapy: MBET and alpha-adrenergic antagonist medication
Combination Therapy	tamsulosin (alpha-adrenergic antagonist medication)	Combination therapy: MBET and alpha-adrenergic antagonist medication

Primary Outcome Measures

Name	Time	Method
Nocturia episodes (voiding diary)	12 weeks	Participant recorded bladder diary over 7-day that included nocturia episodes

Secondary Outcome Measures

Name	Time	Method
Sleep quality	12 weeks	Pittsburgh Sleep Quality Index
Bother from nocturia	12 weeks	American Urological Association 7 symptom index accompanying bother index; specific question on nocturia
Symptom-specific quality of life measure	12 weeks	The International Consultation on Incontinence Nocturia Quality of Life Instrument (ICI-NQOL)
Nocturia episodes (self report)	12 weeks	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.

Trial Locations

Locations (2)

Atlanta VA Medical Center; 🇺🇸 Atlanta, Georgia, United States

Birmingham VA Medical Center; 🇺🇸 Birmingham, Alabama, United States