Efectividad de la terapia neuroadaptativa scenar© para el tratamiento de la incontinencia urinaria de urgencia y de la incontinencia mixta con predominio de urgencia

Zusammenfassung

Introduction: Urge urinary incontinence (UUI) has been underdiagnosed and undertreated throughout history. It affects up to 20% of women over 65 years of age, producing a strong negative impact on their quality of life. Despite this, enough attention is still not paid to this pathology by health professionals. In addition, there are currently no proper therapeutic options for this pathology. Today, the reference treatment are chronic drug therapies (antimuscarinic or β3-adrenergic). However, adherence to these treatments is low due to their moderate efficacy and side effects. For all these reasons, new treatments for UUI should be investigated. Neuromodulation for the treatment of UUI has been widely used. In the present moment there are two approved neuromodulation treatments for this indication: Neuromodulation of the posterior tibial nerve (NMPT) and Neuromodulation of sacral roots (NMSR). The aim of this clinical trial is to evaluate the efficacy of neuroadaptative therapy (NAT) for the treatment of UUI. It is the first non-invasive and painless neuromodulation therapy used for UUI. Material and methods: This randomized, prospective, placebo-controlled, single-blinded, and thirdparty blinded trial has been designed to compare the efficacy of TNA for the treatment of UII. The target population of this study are women between 18 and 80 years of age, with a previous diagnosis of UII or mixed incontinence (MI) with urgency predominance. All the patients included had been previously treated with 1st or 2nd line treatments unsuccessfully, or they were not candidates for these treatments for different reasons. TNA will be applied using a specific device called SCENAR by non-invasive and painless stimulation. A particular application protocol has been designed for this assay. Patients will be divided into two groups through a randomization process: experimental group (active SCENAR) and control group (non-active SCENAR). Weekly sessions will be held until a response or failure is obtained, or until a maximum of 8 sessions are completed. For data collection, each patient will auto-fill weekly a voiding diary (Annex V), the ICIQ-SF questionnaire (Annex II) and the Sandvik questionnaire (Annex I), together with the rest of secondary variables. The data collected will be analyzed using the statistical program R Ver.3.5.1. Objectives: Principal objective: Analyze the efficacy of TNA versus placebo for the treatment of UUI and MI with urgency predominance. The percentage of patients with response (partial or complete) will be used, as well as the scores obtained in the Sandvik (Annex I) and ICIQ-SF (Annex II) questionnaires. Secondary objectives: ▪ Number of urgency episodes not associated with leaks, their Intensity, Episodes of nocturia and Time between micturitions. ▪ Impact on quality of life assessed by Potenziani test (Annex III). ▪ Patient Satisfaction. ▪ Number of sessions to obtain response. ▪ Maintenance of response during a period of 1, 3 and 6 months. ▪ Maintenance through the follow-up other secondary variables such as the Number of urgency episodes, Nocturia, Time between micturitions and score on Potenziani test. ▪ Epidemiological variables that behave as predictors of response. ▪ Appearance of possible adverse reactions. Results: A total of 66 patients were recruited between February 2019 and May 2021. Of these 66 patients, 33 were randomly assigned to the treatment group and the other 33 to the control group. The mean Age and Weight were 61 years old and 71 kg, respectively. The mean Body mass index (BMI) was 27. Most of the patients (76%) had no history of surgery or previous pelvic pathology. Of the total of 66 patients included in the study, 55 (83%) had pure UUI diagnosis, while the other 11 (17%) patients had MI with urgency predominance. 87% of the patients in the placebo group and 72% in the experimental group had been previously treated with pharmacological treatment unsuccessfully. The randomization process resulted in two homogeneous groups. Pre-treatment analysis of the severity grade of UI showed that most of the patients had moderate-severe UI. The mean Sandvik score was 4.89 and the mean ICIQ-SF score 14.67, with a homogeneous distribution of these variables. NAT applied using SCENAR device proved to be effective compared to placebo; with an immediate improvement rate of 70% and a complete cure rate of 63% in the treatment group. In the control group 48% of the patients had a complete response. Treatment group was superior to control in the reduction of scores of both questionnaires (ICIQ-SF and Sandvik). Patients that received NAT were more satisfied than those who received placebo. The other secondary variables analyzed (Urgency episodes, Intensity, Nocturia, Time between micturitions) showed similar improvement rates. For this reason, it could not be demonstrated that NAT was superior to placebo in these cases. NAT group required 2.4 sessions on average to achieve partial response (PR) and 4.3 sessions to achieve complete response (CR). In the experimental group the treatment effect was maintained at 6 months in 55% of the patients, while in the control group it was only sustained in 33% of the patients. NAT group showed higher rates of response at all measurement times (1, 3) during the follow-up. Likewise, the ICIQ-SF and Sandvik values were also lower in the treatment group during the 1st, 3rd, and 6th month of follow-up. Again, the only secondary endpoint for which NAT emerged superior to placebo after 6 months was Satisfaction. Both number of Urgency episodes and Potenziani test score showed similar improvement during the follow-up, therefore it could not be demonstrated that NAT was superior to placebo. Nocturia variable did not show improvement at 6 months in either of the groups. Finally, the variable Time between micturitions paradoxically showed lower value in the placebo group. Age was the only predictor factor of response that could be detected. It was found that the probability of a positive response to treatment at 6 months decreased for each year of age increased. Conclusions: 1. NAT has been shown to be effective compared to placebo in reducing the number and severity of daily leaks associated with urinary urgency; as well as in improving the quality of life of patients with UII or MI with urgency predominance, fulfilling the main objective of this study. 2. The NAT group showed better scores in the secondary endpoint Satisfaction compared to the control group, both at the end of the treatment and after 6 months of follow-up. However, NAT did not show superiority in the rest of the secondary variables (daily urgency episodes, nocturia, time between micturitions, Potenziani test) neither at the end of the treatment nor during follow-up. 3. Patients who received NAT required an average of 2.4 sessions to achieve PR and 3.9 sessions to achieve CR. 4. NAT showed better results at 6 months, with higher response rates and lower ICI-SF and Sandvik scores at all measurement times in the treatment group. 5. Age was the only predictor factor for response, showing that the older the age, the lower the probability of response to NAT. 6. No adverse effect or complication associated with NAT were registered during the development of this clinical trial.