January 1, 2019
Bioelectrical Stimulation for the Treatment of Lower Urinary Symptoms:
A Randomized Controlled Trial.
Cristiane Carboni, MSC,
Porto Alegre, Brazil
Dysfunction of the lower urinary tract, including incontinence is a very common clinical problem effecting millions of men and women of all ages. Regenerative medicine has a potential to provide a hope for the recovery of lost tissue and organ functions. In urology, regenerative medicine approaches include for the treatment of lower urinary tract or bladder dysfunctions (1), which can be caused by several diseases altering the normal cellular and extracellular matrix (ECM) compartments which accomplish the role of storage and voiding. The urothelium is necessary to prevent the passage of hypertonic urine to the blood and the exchange of toxic metabolites. In a state of homeostasis, adult urothelial cells are quiescent, however, if the urothelium is damaged by an acute lesion or a exposure to toxins, a rapid process of exfoliation and regeneration is induced (2).
The normal functioning urinary bladder is composed of two main parts: a compliant muscular wall and a highly specialized urothelium. It is well know that the pelvic floor muscles (PFM) play an important roll in the management of lower urinary tract symptoms as well (LUTS) (3). When the bladder is damaged, all these properties must be taken into account for a global functional recovery (4).
The mechanism of action of bioelectrical stimulation (BES) for lower urinary tract dysfunction was initially investigated in animal models, where it caused bladder relaxation by inhibiting the parasympathetic motor neurons. In animal model BES revealed that stress urinary incontinence (SUI) mice exhibit disordered collagen metabolism and corresponding changes in the TGF-β1-Smad2/3 pathway. After BES therapy, collagen levels increased and the TGF-β1-Smad2/3 pathway was activated in response to mechanical strain. These results indicate that collagen metabolism and the TGF-β1-Smad2/3 pathway are potentially involved in the pathogenesis of SUI as well as in the response to BES therapy (5).
Other studies showed that BES causes contractions of the pelvic floor, increasing the number of muscle fibers with rapid contraction (6). The BES also increases the blood flow to the urethra and PFM, improving the neuromuscular connections, muscular fiber function, genital atrophy improving the mechanism of urethral closure (7),(8) and also induces epithelial cell migration, macrophages, mast inhibition, fibroblasts proliferation and motor axonal regeneration (9).
BES is widely used for overactive bladder syndrome (OAB). The effect of BES in afferent pathways provides a preganglionic central inhibition of bladder’s motor neuron influencing the detrusor activity, but the effects of this therapy in the sacral region are better known. In animal models it has been observed bladder relaxation by the inhibition of parasympathetic motor neurons (10). Remembering that OAB usually occurs with weakness of the pelvic floor muscles too (11).
Considering that BES might be an opportunity to treat bladder dysfunction by the creation of a tissue regeneration we propose this study using intravaginal delivery of BES on the bladder function and LTUS.
The present study aims to evaluate the delivery of BES on the bladder function and LTUS.
To evaluate clinical parameters of patients with LUTS and related than to the questionnaires applied.
For this randomized clinical trial, 30 patients will be selected from a private physician’s office of in the city of Porto Alegre / RS. Each patient will serve as their own control with two-months documentation using the validated questionnaires PRAFAB-score, OAB-V8 and Patient Global Impression of Improvement (PGI-I). The intervention period will last 8 weeks. And 2 months follow up after the end of treatment to see how long the benefit lasts without ongoing treatment. Evaluation will be performed before the intervention period (pre-intervention), and after the intervention period (post-intervention and follow up) for all the participant. BES effectiveness as a treatment of LUTS will be evaluated using the validated questionnaires: PRAFAB-score, OAB-V8, and PGI-I. Randomization will be carried out in two steps: generation of random numbers in each group, using the RANDOM subroutine of the PEPI software suit (computer programs for urologist); and allocation concealment, pacing numbers in letter-sized manila envelopes. Participants will be randomly assigned to three groups: intravaginal BES (IV), parasacral electo acupuncture (PEA) and percutaneous tibial nerve stimulation. The intravaginal bioelectrical stimulation will last 30 minutes with intensity up to the motor threshold, twice a week for 8 weeks.
Randomized Clinical Trial
Data collection location
Private clinic: Pelvic floor world
Number of Subjects: 30 women, 18 years of age or older, with symptoms of stress, urge or mixed urinary incontinence of more than 3 months’ duration.
- Women, 18 – 80 age
- Symptoms of stress, urge or mixed urinary incontinence of more than 3-month duration.
- Willing and able to sign the Informed Consent
- Able to attend all clinic visits defined in the protocol
- Persistent urinary tract infection (positive urine culture after antibiotic treatment)
- Recurrent urinary tract infection (within 4weeks after treatment)
- Bladder pathology or dysfunction because of fistula, tumor, pelvic irradiation, neurological or other
- chronic conditions (diabetes mellitus, Parkinson’s disease)
- Any incontinence treatment during the past 6months,
- Genital prolapse to, or beyond, the introitus,
- Cardiac pacemaker or internal defibrillator
- Cognitive impairment or insufficient mental condition/cognition.
Annexes 1 – PRAFAB score
PRAFAB score: The patient was asked to give the most appropriate answer;
only one answer per section was possible
1 I never use pads for urinary incontinence
2 I occasionally use pads or have to change underwear
3 As a rule I use pads or have to change underwear more than once a day
4 I always use pads for urinary incontinence
1 My loss of urine is limited to an occasional drop
2 My loss of urine can sometimes be as much as a teaspoon
3 My loss of urine is enough to really wet my pads and/or clothing
4 My loss of urine usually completely soaks my pads and/or clothing
Frequency: Involuntary loss of urine occurs
1 Once a week or less
2 More than once but less than three times a week
3 More than three times a week but not every day
4 Every day
Adjustment: My urinary incontinence
1 Does not inhibit me in my daily activities
2 Made me quit some activities like sports or other strenuous exertion
3 Made me quit most activities that provoke my urinary incontinence
4 Prevents me from leaving the house altogether
1 I am not really bothered by my urinary incontinence
2 My urinary incontinence is an inconvenience but not a real problem
3 My urinary incontinence makes me feel unclean
4 I am disgusted with myself because of my urinary incontinence
Annexes 2 – OAB-V8
Annexes 3 – Patient Global Impression of Improvement
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- Yani MS, Wondolowski JH, Eckel SP, Kulig K, Fisher BE, Gordon JE, et al. Distributed representation of pelvic floor muscles in human motor cortex. Sci Rep. 2018;8(1):1–16.
- Serrano-Aroca Á, Vera-Donoso CD, Moreno-Manzano V. Bioengineering approaches for bladder regeneration. Int J Mol Sci. 2018;19(6):1–26.
- Vallinga MS, Spoelstra SK, Hemel ILM, van de Wiel HBM, Weijmar Schultz WCM. Transcutaneous Electrical Nerve Stimulation as an Additional Treatment for Women Suffering from Therapy‐Resistant Provoked Vestibulodynia: A Feasibility Study. J Sex Med [Internet]. 2015 Jan;12(1):228–37. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1743609515308985
- Fall M, Lindström S. Electrical stimulation. A physiologic approach to the treatment of urinary incontinence. Urol Clin North Am [Internet]. 1991 May;18(2):393–407. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2017820
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