Impact of Behavioral Treatment of Insomnia on Nighttime Urine Production
Phase: NA
Conditions: Sleep Fragmentation, Poor Quality Sleep, Nocturia, Nocturnal Enuresis
Sponsor: University of Pittsburgh

October 30, 2018 
 
Impact of Behavioral Treatment of Insomnia on Nighttime Urine 
Production 
University of Pittsburgh STUDY19110063 
NCT03883724 
INTRODUCTION 
Nocturnal polyuria (NP) has long been known to be a major contributor to nocturia in the 
elderly. NP has a strong bidirectional relation with poor sleep especially in the elderly; 
however, to the best of our knowledge, an intervention directed solely at sleep has never 
been tried for NP. Our previous studies have shown that improving sleep with BBTI 
improves nocturia. However, we do not know the mechanisms by which behavioral sleep 
treatments improve nocturia. The proposed study will be the first to directly examine two 
plausible mediators: first uninterrupted sleep period (FUSP) and NP. The knowledge 
gained from this study can help identify 1) impact of sleep intervention on nighttime urine 
production, and 2) mechanisms by which sleep intervention improves nocturia 
 
STUDY OVERVIEW 
This pilot study will provide critical preliminary data regarding the relation between sleep 
and nighttime urine production in seniors by: 1) examining the impact of behavioral sleep 
treatment (BBTI- brief behavioral treatment of insomnia) on nighttime urine production- 
NP and 2) exploring the potential mechanisms by which BBTI impacts nocturia. To 
address the proposed aims we will perform a randomized controlled pilot trial of 60 
healthy community-dwelling men and women aged 65 and over with nocturia and NP. 
The participants will be randomized to receive the 4-week behavioral sleep intervention 
BBTI by a trained therapist or an information control intervention. The participants will 
undergo detailed sleep and bladder assessments pre- and post-intervention to assess 
the effect of treatment. Data from this study will provide feasibility and pilot data for a 
subsequent, larger, and more definitive trial. 
 
Outcome measures: 
1) Change in NP- measured by NPi- nocturnal polyuria index=(nocturnal urine 
volume/24-hour volume)*100 
2) Change in nocturia frequency 
3) Change in FUSP or duration of uninterrupted sleep before the first awakening to void 
 
 

October 30, 2018 
 
STUDY FLOW /STUDY PROTOCOL 
 
Study Flow Chart 
Screening 
Baseline assessment 
R 
A 
N 
D 
O 
M 
I 
S 
A 
T 
I 
O 
N 
Intervention 
Post-
intervention 
assessment 
 
Visit 1 
In-home 
Assessments 
BBTI 
↓ 
↓ 
↓ 
↓ 
Sleep/ Bladder 
diary  
Z-machine  
ISI 
Wk 1 
Wk 2 
Wk 3 
Wk 4 
Session 
Tele 
call 
Session 
Tele 
call 
Telephone 
Screening 
Apnea 
Link 
Plus® 
Detailed 
history & 
physical 
Sleep/  
Bladder diary 
Z-machine 
 
 
 
 
 
 
IC 
↓ 
↓ 
↓ 
↓ 
Wk 1 
Wk 2 
Wk 3 
Wk 4 
 
Tele 
call 
 
Tele 
call 
 
  
 

October 30, 2018 
 
Screening  
Screening procedures include: a) telephone interview and b) Visit 1 to study research suite - 
Continence Research Unit at UPMC Montefore Hospital. If the subject is interested and 
qualifies, then the other visits are scheduled.  
Telephone Interview 
Use IRB approved telephone script to determine eligibility (5-20mins; study nurse/coordinator)  
ApneaLink mailed to participants who screened eligible upon telephone interview 
 
Visit 1 
2 hour; study nurse; in-person 
1. Obtain informed consent and sign document. 
2. Questionnaires:  
• 
Medical and Surgical history 
• 
Current medication 
• 
Current incontinence 
• 
ISI 
• 
MoCA (paper) 
3. Uroflow and dip (at appropriate bladder fullness)  
4. Measure flow rate and volume of normal void 
5. Post-void residual measurement by ultrasound 
6. Physical examination: Short physical examination. 
7. Sleep/ bladder diary: Explain 3 day sleep and voiding diary instructions. 
8. Zmachine: watch instruction video. The device to be worn on the 3rd night of voiding 
diary 
9. Schedule visit 2 with enough time to complete diary. 
 
Visit 2 
Randomization 
1. Follow study procedure according to the group randomized to. 
 
Telephone follow-up 
Week 2 after the visit 2- both groups (BBTI and Control) 
Week 4 after the visit 2- both groups 
 
Visit 3 
For participants randomized to BBTI group  
 
Post intervention 
4 weeks post visit 2  
1. Sleep/ Bladder diary (send in mail) 
2. Zmachine (send in mail) 
3. ISI- completed telephonically. 
 
 

October 30, 2018 
 
Inclusion/exclusion criteria 
 
For this study researchers shall enroll: ambulatory and functionally-independent community-
dwelling men and women 
aged 65+ years, with nocturia ≥2/night. 
 
Exclusion criteria: 
• Unstable or acute medical or central nervous system conditions 
• Untreated, current, severe psychiatric condition 
• Untreated, current, severe overactive bladder syndrome 
• Post void residual > 30ml 
• Sleep apnea with AHI≥15 
• Currently diagnosed and/or treated Obstructive Sleep Apnea, Restless Legs Syndrome, 
parasomnia 
• CHF, by exam or NT-proB natriuretic peptide (NT-proBNP)> 30 pmol/L56 
• Chronic kidney disease, stage III-V (eGFR<60) 
• >14 alcohol drinks per week 
• >3 caffeinated drinks (~300mg) per day 
 
 

October 30, 2018 
 
Statistical Analysis Plan 
 
Randomization: After all baseline assessments are complete, researchers will randomize 
the participants in to the intervention groups in a 1:1 ratio, with random block sizes chosen 
from small even numbers, stratified by severity of baseline nocturia (≤3 or >3/night . To 
prevent educated guessing, the study statistician will reveal exact details of blocking 
strategy only at study completion. 
 
Data Analysis: In addition to statistical significance, researchers will employ descriptive 
statistics and graphical techniques to draw conclusions. Specifically, as appropriate for a 
pilot study, researchers will focus interpretations on magnitudes of effects from standard 
statistical methods rather than their p-values, and apply graphical techniques such as 
needle plots to represent data at the individual level rather than based on averages. 
Researchers will use SAS® version 9.3 (SAS Institute, Inc., Cary, North Carolina) 
software, intention-to-treat philosophy, and multiple imputation for missing data in all 
inferential analyses. 
 
First, researchers will compare baseline characteristics between the group using 
independent samples t-, Wilcoxon rank sum, chi-square and Fisher’s exact tests, as 
appropriate. Any significant differences will be used as additional covariates in sensitivity 
analyses. Second, researchers will fit a series of analysis of covariance (ANCOVA) 
models with pre- to post-intervention change in each outcome as the dependent variable, 
intervention group as the independent factor of interest, and baseline value of outcome as 
a covariate. Magnitude and significance of intervention group term will serve as evidence 
for Aim 1 efficacy hypotheses. Third, for Aim 2, researchers will begin by exploring 
correlations of pre- to post-intervention changes in nocturia with those in FUSP and NPI. 
In keeping with Baron and Kenny’s framework for mediation analysis, researchers will add 
FUSP change and NPI change (both individually and together) as additional independent 
variables to the Aim 1 ANOVA models. Any subsequent reduction in intervention effect 
will be interpreted as supporting the Aim 2 mediation hypotheses. Statistical significance 
of the extent of mediation will be obtained using %SOBEL, %INDIRECT and %MEDIATE 
SAS® macros, as appropriate.