Role of Protopine and Nuciferine in the management of nocturia, urgency and dysuria in pre- and post-menopausal women: a prospective pilot study.

Abstract
Objectives: Nocturia was commonly treated with drugs burdened with high costs and numerous side effects; in fact, more than 70% of patients drop out of long-term treatment. Protopine and Nuciferine are two alkaloids that have different effects on the neurotransmitter receptors involved in the regulation mechanism of the onset of urinary stimuli. The aim of the study is to evaluate the efficacy in controlling primarily nocturia and secondarily urgency and dysuria after three months of treatment with combination therapy of protopine and nuciferine syrup.
Design: This is a prospective cohort study in which all patients were diagnosed with overactive bladder syndrome (OAB) and the presence of symptoms: nocturia, urgency, and dysuria. 30 patients are administered 10 ml/die (16.6 mg of Nuciferine – 0.09 mg of Protopine) of syrup for 3 months. Patients are evaluated at baseline (T0) with the ICIQ questionnaire (International Consultation on Incontinence), VAS (Visual Analogue Scale) for the evaluation of dysuria, PPIUS (Patient Perception of Intensity of Urgency Scale) and at 3 months (T1) with the PGI-C Scale (Patients' Global Impression of Change), PPIUS, VAS and ICIQ. 
Participants: Women with diagnosis of OAB; presence of nocturia, urgency, and dysuria symptoms agreeing to undergo treatment and compiling informed consent; absence of contraindications to the use of active ingredients.
Setting: Patients were recruited at (T0) during the visit to the Uro-Gynecology clinic of the University of 'Campus Bio-Medico' and visited again 3 months (T1) after the initiation of therapy.
Methods: We explored survey data by descriptive statistics: in particular, continuous values (i.e., ICIQ) have been summarized by mean and standard deviation, discrete ordinal values (i.e., VAS, PPIUS, and bladder diary parameters at T0 and T1) by median, minimum, and maximum reported scores. Where we could assume normality in distribution, assessed by the Shapiro-Wilk test and the evaluation of the QQ plot, we compared the observation T0 and T1 with the paired Student's t test, otherwise we tested differences in distribution with the paired Mann–Whitney U test. 
Results: Thirty patients completed a three-month therapy. The ICIQ, VAS questionnaires for the assessment of dysuria, both, reported an improvement in dysuria at T1 (p< 0.001). The PPIUS questionnaire reported an improvement in urinary urgency in T1 (p<0.001). The PGI-C scale in T1 indicated an improvement in symptoms: 93% for nocturia, 70% for urinary urgency, and 63% for dysuria. 
Limitations: The weaknesses are the small number of patients, as a pilot study, the study design is not randomized with placebo and without blinding and the short follow-up. 
Conclusions: Protopine and Nuciferine can be an interesting alternative to primarily treat and reduce nocturia episodes, in addition to improving OAB-related urgency and dysuria. 
(Prot. N. Proto-Gyn-Uro 007/06.02.2019)
