Protocol for a prospective, randomized study on neurophysiological assessment of lower urinary tract function in a healthy cohort

Abstract

BackgroundLower urinary tract symptoms are highly prevalent and a large proportion of these symptoms are known to be associated with a dysfunction of the afferent pathways. Diagnostic tools for an objective and reproducible assessment of afferent nerve function of the lower urinary tract are missing. Previous studies showed first feasibility results of sensory evoked potential recordings following electrical stimulation of the lower urinary tract in healthy subjects and patients. Nevertheless, a refinement of the methodology is necessary.MethodsThis study is a prospective, randomized trial conducted at Balgrist University Hospital, Zürich, Switzerland. Ninety healthy subjects (forty females and fifty males) without lower urinary tract symptoms are planned to be included in the study. All subjects will undergo a screening visit (including standardized questionnaires, 3-day bladder diary, urinalysis, medical history taking, vital signs, physical examination, neuro-urological examination) followed by two measurement visits separated by an interval of 3 to 4 weeks. Electrical stimulations (0.5Hz-5Hz, bipolar, square wave, pulse width 1 ms) will be applied using a custom-made transurethral catheter at different locations of the lower urinary tract including bladder dome, trigone, proximal urethra, membranous urethra and distal urethra. Every subject will be randomly stimulated at one specific site of the lower urinary tract. Sensory evoked potentials (SEP) will be recorded using a 64-channel EEG cap. For an SEP segmental work-up we will place additional electrodes on the scalp (Cpz) and above the spine (C2 and L1). Visit two and three will be conducted identically for reliability assessment.DiscussionThe measurement of lower urinary tract SEPs elicited by electrical stimulation at different locations of the lower urinary tract has the potential to serve as a neurophysiological biomarker for lower urinary tract afferent nerve function in patients with lower urinary tract symptoms or disorders. For implementation of such a diagnostic tool into clinical practice, an optimized setup with efficient and reliable measurements and data acquisition is crucial. In addition, normative data from a larger cohort of healthy subjects would provide information on variability, potential confounding factors and cut-off values for investigations in patients with lower urinary tract dysfunction/symptoms.Trial registrationClinicaltrials.gov; Identifier: NCT02272309.

Scalp Topography of Lower Urinary Tract Sensory Evoked Potentials

“…Healthy subjects were recruited through postings and advertisements on internet platforms. For further details see van der Lely et al ( 2019b ) and van der Lely et al ( 2016 ). All included subjects fulfilled predefined cut-offs (Table 1 ).…”

Does electrical stimulation in the lower urinary tract increase urine production? A randomised comparative proof-of-concept study in healthy volunteers

“…This proof-of-concept study was embedded in the frame of a LUTSEP study (S1 Study protocol) [10]. The corresponding power analysis outlined in our protocol paper [10] revealed a total inclusion number of 90 subjects.…”

“…This proof-of-concept study was embedded in the frame of a LUTSEP study (S1 Study protocol) [10]. The corresponding power analysis outlined in our protocol paper [10] revealed a total inclusion number of 90 subjects. Forty females and fifty males were scheduled for two separate (interval of 29.0±8.5days) but identical visits and randomly assigned to one of the following LUT stimulation groups (1:1:1:1:1): bladder dome (BD), trigone (TG), proximal urethra (pUR), membranous urethra (mUR, additional location in males considering gender-specific anatomical characteristics), and distal urethra (dUR) (Figs 1 and 2).…”

“…Exclusion criteria were lower urinary tract symptoms (LUTS) [11], urological or neurological pathology, pregnancy, current or recurrent urinary tract infection (UTI), hematuria, previous surgery for urological or neurological reasons, and regular intake of any kind of prescribed or non-prescribed medication (except contraceptives). This was assessed on the basis of a complete medical history interview, vital signs, physical and neurological examinations (including examination of urogenital sensation, bulbocavernosus reflex, anal reflex, anal sphincter tone, and anal squeeze response), free uroflowmetry, post-void residual, Montreal-Cognitive-Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS), International Prostate Symptom Score (IPSS) and a 3-day bladder diary (BLD) [10] using predefined cut-offs (Table 1).…”

“…The BLDs were completed during three independent days, recording the time points and volumes (mL) of drinking and micturition, as well as the number of incontinence episodes, pad usage, and pain levels associated with urine storage and/or micturition (0 to 10). Additionally, standardized urological questionnaires (International Consultation on Incontinence Modular Questionnaire modules (ICIQ-FLUTS, ICIQ-MLUTS) and Overactive Bladder Questionnaire short-form (Swiss German OAB)) were completed [10]. All questionnaires and the bladder diary were independently completed by the participants.…”