Idiopathic overactive bladder syndrome (OAB) is a common disorder associated with significant morbidity and economic burden. Nocturia, defined by voids which disrupt sleep, is responsible for some of the most important adverse consequences of OAB. Yet, little research has been carried out on the nocturnal physiology of OAB patients and the mechanisms of the associated nocturia are poorly understood. Further, it remains uncertain whether mechanisms associated with daytime OAB symptoms are relevant to nocturia because changes in physiology occur with sleep and because there are other potential causes of nocturia in OAB patients, most notably nocturnal polyuria (NP). There is a pressing need to establish the mechanisms of nocturia in OAB because nocturia responds less well to treatment than daytime OAB symptoms. This application proposes a study which aims to address this need by evaluating promising biomarkers of key physiologic mechanisms associated with nocturia in OAB. Our focus is on one of the two systems which control bladder function: the autonomic nervous system (ANS). The proposed study will test the hypothesis that nocturia in OAB patients may reflect two primary processes: 1) detrusor muscle instability leading to ANS dysfunction which may culminate in detrusor overactivity (DO);and 2) increased nighttime bladder filling, such as occurs in NP, that triggers ANS dysfunction. We will test this hypothesis by obtaining measures of the key components of our model (heart-rate variability assessment of ANS, cystometrography to indicate DO, maximum void volume as an indicator of detrusor instability, and nocturnal urine production rate) coincident with polysomnography during a single night in the sleep laboratory in: OAB patients with nocturia (N=76);NP patients without OAB (N=56);insomnia patients (N=32);and controls (N=25). Ultimately, this work could lead to the development of objective biomarkers of the pathological processes of nocturia in OAB patients for future research and could provide a basis for improving the treatment of patients with this important but inadequately treated public health problem.

Public Health Relevance

Nocturia is a common symptom of idiopathic overactive bladder syndrome (OAB) and the source of some of its most important adverse consequences including sleep disturbance, falls, and daytime sleepiness. Yet, our current capacity to effectively treat nocturia in OAB remains limited. This is due, at least in part, to a lack of understanding of the pathophysiology of nocturia in OAB. Through better characterizing the physiologic mechanisms of OAB-related nocturia, the proposed study has the potential to lead to the development of more effective treatments for this condition and thereby improve the lives of many patients with nocturia associated with OAB.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Urologic and Kidney Development and Genitourinary Diseases Study Section (UKGD)
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Mullins, Christopher V
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Duke University
Schools of Medicine
United States
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Krystal, Andrew D (2010) Antidepressant and Antipsychotic Drugs. Sleep Med Clin 5:571-589