Non-invasive NESA Neuromodulation Versus Transcutaneous Posterior Tibial Nerve Stimulation for the Treatment of Overactive Bladder
Phase: NA
Conditions: Bladder Dysfunction
Sponsor: Daniel David Álamo Arce

University of Valencia and University of Las Palmas de Gran Canaria 
 
 
 
 
04th April 2025
Paloma Blasco-Sonora; Laura Fuentes-Aparicio; Raquel Medina-Ramírez
NON-INVASIVE NESA 
NEUROMODULATION VERSUS 
TRANSCUTANEOUS POSTERIOR 
TIBIAL NERVE STIMULATION FOR 
THE TREATMENT OF OVERACTIVE 
BLADDER 
Brief tittle: NESA NEUROMODULATION VERSUS TRANSCUTANEOUS POSTERIOR TIBIAL 
STIMULATION Acronym: NESATIBIAL NCT: ID not yet assigned  
 

NON-INVASIVE 
NESA 
NEUROMODULATION 
VERSUS 
TRANSCUTANEOUS POSTERIOR TIBIAL NERVE STIMULATION 
FOR THE TREATMENT OF OVERACTIVE BLADDER 
(NESATIBIAL) 
 
ABSTRACT 
Objectives: To evaluate the effect of non-invasive NESA neuromodulation compared to 
posterior tibial stimulation in patients with overactive bladder. compared to posterior 
tibial stimulation, with same-day exercises and patient education on quality of life, 
symptoms, discomfort and sleep. day of the session and patient education on quality of 
life, symptoms, discomfort and sleep. 
Methods: Twenty-four patients (24 women), aged 38-85 years with overactive bladder 
were included in this experimental clinical study. Each patient attended ten sessions two 
days a week. Patient health was measured using SF-36, sleep quality using the Pittsburgh 
questionnaire, perception of UI symptoms and patient quality of life using the ICIQ-SF 
questionnaire. All these variables were measured before, immediately after the ten 
sessions and at two months after the end of treatment. 
Results: Mann-Whitney U test where, in general, improvements were obtained in all the 
variables, although not significantly in the variables, although not significant over time 
in both groups, except in the assessment of discomfort assessment (CACV) and the SF-
36, which only showed an improvement in the non-invasive group, NESA vs. Tibial group 
in the quality of health, with a P-value of P=0.035. 
Conclusion: The two treatments generated an improvement in quality of life, symptoms, 
discomfort and quality of life, discomfort and in the quality of sleep in the short term; 
obtaining better results in the non-invasive NESA group in the quality of health, with a P 
value of 0.035. group in quality of life and discomfort in women with overactive bladder. 
 
 
 
 
 
 
 
 
 
 

 
INTRODUCTION 
La vejiga hiperactiva (VH) es un síndrome caracterizado por un aumento de la frecuencia 
miccional acompañado de urgencia miccional y asociado en ocasiones con incontinencia 
urinaria de urgencia. Es un proceso crónico que tiene un importante impacto en la calidad 
de vida de los pacientes que lo padecen, con una prevalencia que aumenta a medida que 
se envejece, llegando al 22% en las mujeres. La Incontinencia Urinaria es un 
padecimiento que producen escapes involuntarios de orina. Existen dos tipos de 
incontinencia, la asociada a los esfuerzos y la incontinencia asociada a la sensación de 
micción urgente no relacionada con los esfuerzos. Este segundo tipo de incontinencia es 
el que se asocia al Síndrome de Vejiga Hiperactiva. El tratamiento de la VH es escalonado, 
con un tratamiento inicial basado en el cambio en el estilo de vida, reeducación vesical, 
ejercicios de suelo pélvico y farmacológico. La neuroestimulación forma parte del 
algoritmo terapéutico recomendado en casos rebeldes al tratamiento inicial. NXSignal 
(www.nesaworld.es) es un sistema de electroestimulación de aplicación superficial que 
administra una estimulación eléctrica pulsátil externa, imperceptible y de características 
similares a las que produce el cuerpo humano. Se aplica sobre las extremidades, mediante 
guantes y tobilleras conectados con electrodos a una consola de control. Este tipo de 
tecnología se usa en la actualidad en el sector de la fisioterapia y el deporte con excelentes 
resultados. Diferentes estudios clínicos han demostrado que las terapias de 
electroestimulación tienen aplicación rutinaria en el tratamiento del Síndrome de vejiga 
hiperactiva. Se propone, por tanto, una alternativa tecnológica a las terapias ya existentes, 
que a diferencia de las técnicas convencionales no es invasiva, no produce contracción 
muscular ni movimiento y emite una microcorriente de intensidad y frecuencia fisiológica 
no perceptible. Este estudio se ha diseñado para valorar de manera objetiva la eficacia de 
la tecnología NXSignal en el Síndrome de Vejiga Hiperactiva con tratamientos ya 
existentes como la estimulación del Tibial posterior con gran evidencia científica en estos 
últimos años.  
El formato de ensayo clínico nos permite dar validez científica a los resultados obtenidos 
y poder confirmar de forma rigurosa su beneficio. Si el resultado de la investigación 
demuestra que el nuevo sistema de neuromodulación es eficaz para tratar el síndrome de 
vejiga hiperactiva, además de la estimulación del Tibial posterior, beneficiaríamos a un 
porcentaje de pacientes que en este momento no responden al tratamiento farmacológico 
y que son candidatos a otros tratamientos más invasivos. 
Los sujetos de este estudio participarán en un ensayo clínico aleatorizado doble ciego para 
demostrar la eficacia de la neuromodulación NXsignal frente la neuromodulación 
transcutánea del Tibial posterior. 
 
 
 
 
 

 
METHODS 
 
General hypothesis: The use of the low frequency electrotherapy system of non-invasive 
Neuromodulation NESA, could neuromodulate the nervous system allowing to regulate 
the physiopathological mechanism of overactive bladder, improving the symptoms of 
quality of life, discomfort and quality of sleep of patients suffering from overactive 
bladder.. 
Objectives: To evaluate the effect of non-invasive NESA neuromodulation compared to 
posterior tibial stimulation in patients with overactive bladder. compared to posterior 
tibial stimulation, with same-day exercises and patient education on quality of life, 
symptoms, discomfort and sleep. day of the session and patient education on quality of 
life, symptoms, discomfort and sleep. 
Ethic 
The methodology of the clinical trial has been specifically designed to obtain answers to 
the stated objectives. The study will be conducted in accordance with the standard code 
of good clinical practice, respecting the current regulations for this type of study and the 
recommendations of the Declaration of Helsinki. Informed consent will be given to all 
patients and the study is approved by the ethics committee of the University of Valencia 
(Cod. 2025-FIS-3870878). 
Subjects and Recruitment: Subjects will be recruited at the physiotherapy office of the 
L'Estiuet clinic in Valencia. After obtaining consent, the patient will be scheduled for the 
application of the intervention two days a week, for 5 weeks for a total of 10 sessions in 
both treatments. Patients who agree to participate will be randomly assigned to one of the 
2 treatment groups (NESA is the NNG group and tibial stimulation is the NTPG group). 
The study will be single-blinded, blinding the allocation of the intervention to which the 
patients have been assigned and to the specialist who collects the information and 
performs the follow-ups. Data analysis will also be performed in a blinded manner. 
Inclusion Criteria: 
• 
Minimum criteria for a primary diagnosis of overactive bladder who have or have 
not received active/alternative treatments for this pathology.  
• 
Patients with previous pharmacological treatments that have not obtained an 
adequate clinical response.  
• 
Patients whose cognitive abilities are competent to participate in the study and are 
able to complete the study questionnaires and have given written consent to 
participate in the study.   
• 
Without further contraindications for electrotherapy treatment such as serious use 
of pacemakers, pregnancy, internal bleeding, poor skin condition (ulcerations, 
wounds...) and/or phobia of electricity. 
Participants will be excluded if they had any of the following criteria: 

• Presence of urinary fistula.  
• Infections in the last 12 months.  
• Haematuria during the trial period.  
• Pregnancy or plans to become pregnant during the study.  
• Pathology of the central or peripheral nervous system (multiple sclerosis, 
Parkinson's disease, etc.).  
• Uncontrolled diabetes.  
• Currently treated with Botox injections for the bladder or within the last year.  
• Current treatment with interstim or currently implanted interstim device.  
• Bladder outlet obstruction.  
• Urinary retention.  
• Treatment with more than two antidepressants and/or multiple benzodiazepines, 
as well as antiepileptics.  
• Contraindications for electrotherapy treatment. All patients signed an informed 
consent form prior to inclusion. 
 
 
Patients were randomised into each of the groups:  
 
Group1: NESA non-invasive neuromodulation (NNG) using the NESA XSIGNAL 
device with exercises on the same day of the session and education providing common 
written instructions not individualised, such as dietary and social advice. 
NNG was performed with the patient supine, using NESA technology with gloves and 
anklets, with a total of 24 electrodes plus a directional electrode performing global 
neuromodulation; NESA is a non-invasive monitoring device, which emits low frequency 
microcurrents (1.3-14.28 Hz, depending on the programme), low intensity (0.1-0.9 mA), 
and low voltage (±3 V) and therefore imperceptible to the patient. Each day a different 
programme was applied. On the first three days, programme 1 (P1) 15 min, programme 
2 (P2) 15 min and programme 7 (P7) 30 min were applied. From the fourth to the sixth 
day, P2 30 min and P7 30 min were applied, ending the rest of the days with P3 30 min 
and P7 30 min. At the same time, SP exercises were performed (on the same day of the 
treatment with a duration of 30 min of the 60 min session), all of this accompanied by 
advice. Programme 1, uses a maximum frequency 7.69 Hz and a minimum frequency of 
3.85 Hz to adapt to the patient and modulate the CNS centrally. Programme 2 and 3 used 
a maximum frequency of 1.96 Hz and a minimum frequency of 1.14 Hz to focus the 
treatment on the ventral and dorsal area and programme 7 used a maximum frequency of 
14.29 Hz and a minimum frequency of 1.92 Hz to focally inhibit the tone and achieve a 
modulation of the parasympathetic autonomic nervous system. 
 
Group 2: Non-invasive posterior tibial neuromodulation (NTPG) with same-day 
exercises and education through common, non-individualised written instructions. 

NTPG was performed by posterior tibial application plus SP exercises (same day of 
treatment) and advice, with the patient supine, using NEUROTRAC MYOPLUS PRO to 
perform TENS for 30 minutes. An electric current with a frequency of 10 Hz and pulse 
duration of 200μs was applied. The intensity was adjusted according to the patient's 
tolerance, with thumb flexion perceptible to visual inspection by the therapist. Two 50 x 
50 MM electrodes were placed along the posterior tibial nerve pathway, one on the sole 
of the foot and the other near the medial malleolus on one leg. The exercises in both 
groups consisted of abdomino-diaphragmatic breathing through tonic contractions 
(taking air, blowing, contracting the pelvic floor while bringing the navel inwards and 
upwards for approximately 7 seconds during the contraction, relaxing the pelvic floor 
without pushing, with a rest time of approximately 4 seconds), and phasic (short but fast 
contractions, 1 second contraction, 5-10 repetitions, with a rest time greater than and 
equal to the work, 10 seconds) during these 30 minutes. The sets and repetitions of the 
exercises were performed depending on the physical condition of each patient. All 
patients performed ten sessions two days a week. 
Measure tools 
Both groups will be provided with a set of reliable and validated questionnaires. All these 
variables will be assessed  before treatment, immediately after the treatment is finished 
and at two months later (follow-up) by a blinded assessor. 
 
The patient's perception of quality of life will be measured using SF-36, which is 
composed of 36 items that assess both positive and negative states of health by asking 
about: Physical Function, Physical Role, Bodily Pain, General Health, Vitality, Social 
Function, Emotional Role and Mental Health. Additionally, the SF-36 includes a 
transition item that asks about change in general health status from the previous year. This 
item is not used for the calculation of any of the scales, but provides useful information 
about the perceived change in health status during the year prior to the administration of 
the SF-36.  10 
 
Sleep quality using the Pittsburg questionnaire, consisting of 19 items that analyse 7 
different components of sleep (subjective sleep quality, sleep latency, sleep duration, sleep 
efficiency, sleep disturbances, use of sleep medication and daytime dysfunction). Each 
item is scored from 0 to 3. The total score of the scale ranges from 0 to 21 points where 
the lower end represents good sleep quality, and the upper end represents poor sleep 
quality.11. 
Perception of frequency, severity of UI and patient quality of life will be assessed using 
the International Consultation on Incontinence Questionnaire (ICIQ-SF) validated 
questionnaire, where the individual's daily experience of urination and incontinence is 
answered with three scored items and one unmarked self-diagnostic item.12 
Bladder symptoms and discomfort will be assessed using the Bladder Control Self-
Assessment Questionnaire (B-SAQ), a validated questionnaire consisting of 8 questions 
grouped into two scales, each with a scale of 0 to 3 points, giving a maximum score of 24 
points (12 in each group).13 
They will be also asked after two months about their satisfaction with the treatment 
received (numerical scale NSR 0 not satisfied -10 very satisfied), whether they continued 
to perform the exercises and whether they had any side effects after the treatment.  

Data analysis 
The statistical data analysis will be performed using statistical SPSS software version 
25.0 (SPSS Inc., Chicago, IL, USA). The normality of the variables will be evaluated by 
the Shapiro–Wilk test. Descriptive statistics are presented as to as mean (standard 
deviation),median (25-75th percentile) or frequencies (percentage), as appropriate.  For 
the inferential analysis to compare among the groups and three different times (T0, T1 
and T2) three-factor ANOVA with repeated measures will be conducted. When the 
ANOVA models indicate significant differences in the main effects, Bonferroni’s 
correction will be applied to avoid type I errors in the multiple comparisons. The α level 
will be set at 0.05 for all tests. 
Effect sizes for the study variables will be measured using Cohen's d and r. According to 
Cohen's d, the effect sizes could be categorized as small (0.20 to 0.49), medium (0.50 to 
0.79), or large (greater than 0.80). For the “r” measure, effect sizes will be classified as 
low (0.10), moderate (0.30), large (0.50), and very large (greater than 0.80). 
 
 
Timing and supervision 
This project is part of a master's thesis. It is estimated to last a total of 8 months, with 1 
month of recruitment, 4 months of treatment, and then 3 months to analyse and prepare 
the article or scientific communication. This project is supervised by two directors who 
will ensure the application of good practices, its registration in the clinical trial and its 
execution. 
 
Contact 
Central Contact Person: Raquel I Medina-Ramírez , PhD. Physiotherapist    0034 
665265685 Ext. 0034    raquel.medina@ulpgc.es 
Central 
Contact 
Backup: Laura 
FUENTES-APARICIO 
, 
PhD. 
Physical 
Therapy    669682391 Ext. 0034    Laura.Fuentes@uv.es 
Overall Study Officials:  
Principal Investigator: Paloma Blasco-Sonora , Physical Therapy    University of Valencia 
Study Director: Laura FUENTES-APARICIO , PhD. Physical Therapy    University of 
Valencia 
Study Director: Raquel Medina-Ramírez , PhD. Physical Therapy    University of Las 
Palmas