Addressing Nocturia in Older Women Utilizing Behavioral Sleep Intervention and Brief Mindfulness

Nocturia, or waking at night to void, and poor sleep are prevalent and comorbid conditions in the elderly. Nocturia affects up to 70% of those over age 60, and over 75% of the older adults with poor sleep report nocturia as the main reason. Nocturia increases risk for falls, fractures, depression, institutionalization, and death. Poor sleep and nocturia have a bidirectional relationship and are mutually exacerbating. Nocturnal polyuria (NP) or excess urine production during sleep is the major contributor to nocturia in the elderly and poor sleep is known to cause NP. Vasopressin and aldosterone peak during sleep, causing sodium and water reabsorption in renal tubuli, which leads to decrease in nighttime urine production. Sleep loss leads to attenuation of the sleep time release of these hormones, resulting in natriuresis and diuresis causing NP.

Brief behavioral treatment of insomnia (BBTI- a brief 4-week, efficacious behavioral treatment for insomnia) is effective in addressing sleep and nocturia. Investigators found in their recently concluded pilot trial among older adults with comorbid nocturia (≥2/night) and poor sleep, that BBTI improved nocturia more than control (-0.9 vs -0.3, p=.016). Compared to control, BBTI improved subjective insomnia severity index (-5.9 vs -2.5, p=.02). Additionally, BBTI also improved NP: % of 24h urine volume excreted at night decreased in BBTI vs control (-7.1±13%, p=.001 vs -4±11, p=.08). Although BBTI is brief and effective for nocturia, adherence to behavioral sleep treatments among patients with chronic conditions (poor sleep, nocturia) is disappointingly low compared to patients with acute conditions, particularly several months after therapy. Moreover, the time and personnel needed to train professionals and to administer the intervention has limited the scalability of this otherwise promising treatment. Alternatives to boost treatment adherence and maintain benefit need to be investigated.

Recently the investigators trialed brief mindfulness (MI) training alone or paired with transcranial direct current stimulation (tDCS) in older women with urinary incontinence to enhance cognitive control over bladder symptoms. Of these women, those who had nocturia (≥1/night) and received MI training alone experienced improvement in nocturia (-0.5±0.6, p=0.005) with a concurrent increase in FUSP (39.8±70.2 minutes, p=0.02). Interestingly, effect of MI on nocturia and FUSP were similar to that seen with BBTI. MI requires only brief training followed by convenient at-home use. It was well liked in our study with an acceptability of 85.6 and compliance of 94.4 on a 1-100 Likert scale indicating MI may be a simpler and scalable modality either alone or to augment BBTI for reducing nocturia in older women.

This study a randomized pilot trial in older women with interrupted sleep due to nocturia to examine the effect of BBTI and MI on nocturia, nighttime urine production, and sleep quality at 4-week (post-intervention) and 3- and 6-months later. The investigators postulate that both interventions, individually and in combination, will be beneficial, and the combined treatment will lead to sustained treatment effects at 3- and 6-months.

The study will include older women with nocturia. Sleep will be assessed subjectively with the Pittsburgh Sleep Quality Index (PSQI) and objectively using Zmachine®, an FDA cleared in-home single channel EEG device, and a 3-day bladder-sleep diary that concurrently assesses sleep and voiding pattern including frequency and volume during day and night. Participants will be randomized to one of the 4 groups in a 2x2 factorial design: i) BBTI, ii) MI, iii) BBTI+MI or iv) control. Participants will repeat the study measures at 4 weeks, and 3- and 6-months.

The study aims to explore the effects of MI and BBTI. Hypothesis: Compared to control, BBTI and/or MI groups will result in greater improvement in 1) nocturia, 2) volume of nighttime urine volume, and 3) sleep quality at 4 weeks with the combined BBTI+MI intervention conferring greater benefits and sustained treatment effects at 3- and 6-months.

This study will be the first RCT to evaluate the effect of BBTI and MI, individually and combined on nocturia and sleep, and to assess durability of benefit. The results will provide novel information regarding the promise of efficient cost-effective, and easy to disseminate means of treating nocturia in older women and facilitate confirmatory trial to provide definitive evidence and develop clinically acceptable treatment protocols.

Inclusion criteria

• Female
• Age > or =65 years
• Nocturia ≥2/night
• Poor sleep (Insomnia Severity Index ≥8)
• MoCA (including trail making) >26

Exclusion criteria

• Conditions that affect bladder function: Multiple sclerosis, Alzheimer's disease, spinal cord injury, urethral obstruction, urinary retention, interstitial cystitis, bladder cancer, radiation to the pelvic area, bladder surgery, current or uncontrolled chronic or recurrent bowel issues, bacterial endocarditis
• cardiac or respiratory disease that limits daily function
• Unstable or acute medical condition:

• Any acute medical condition that requires immediate treatment such that it would interfere with the study protocol; Each instance will be assessed on a case-by-case basis by our study physician who may postpone a participant's enrollment; stably managed chronic conditions are exempt from this exclusion.
• Untreated, current, severe psychiatric condition (assessed during Visit 1a- medical history)
• Post void residual ≥ 200ml- assessed during baseline visit
• Currently diagnosed and/or untreated obstructive sleep apnea, untreated restless leg syndrome, untreated parasomnia
• Untreated or poorly controlled fluid overload conditions like CHF, diabetes