Non-invasive Nerve Stimulation for Inhibition of Bladder Incontinence in Spinal Cord Injured Subjects.

• Sponsor: Taipei Medical University (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03877432
• Collaborator: (none)
• Enrollment: 10
• Arm: 1
• Anticipated Duration (Months): 57.3

Study Details

Study Description

Brief Summary

Investigators will test S2-S4 dermatome stimulation with spinal cord injury (SCI) individuals using intermittent catheterization to estimate the clinical impact on bladder capacity and continence. For individuals with SCI using intermittent catheterization, investigators hypothesize that dermatome stimulation will decrease bladder spasm frequency and intensity, and reduce bladder incontinence chronically. The goal of this study is to provide objective evidence for the assertion that dermatome stimulation chronically decreases bladder activity and therefore the unwanted side effects of neurogenic bladder. This project will improve the understanding of the neurophysiology of afferent-mediated neural pathways that affect bladder function, and translate recent advances discovered in animal and human studies into clinical research and treatment. The ability to void safely and effectively by electrical stimulation without cutting sacral nerves or the external urethral sphincter would be a major advance. A socially acceptable, predictable and reliable device for reducing incontinence would be widely used and improve quality of life.

Condition or Disease	Intervention/Treatment	Phase
Spinal Cord Injuries	Device: Dermatome stimulation	N/A

Detailed Description

Investigators will test S2-S4 dermatome stimulation with SCI individuals using intermittent catheterization to estimate the clinical impact on bladder capacity and continence.

For individuals with SCI using intermittent catheterization, investigators will verify that S2-S4 dermatome stimulation is acutely effective at reducing hyper-reflexive bladder activity during bladder filling. Investigators hypothesize that S2-S4 dermatome stimulation will reduce the number and severity of incontinent episodes, increase bladder capacity, and increase the volume catheterized. By comparing the extended outcomes to the acute laboratory outcomes obtained by ourselves and others, investigators can assess the feasibility of acute urodynamics to identify subjects for implanted devices or future studies.

For individuals with SCI using intermittent catheterization, investigators hypothesize that dermatome stimulation will decrease bladder spasm frequency and intensity, and reduce bladder incontinence chronically. The goal of this study is to provide objective evidence for the assertion that dermatome stimulation decreases bladder activity and therefore the unwanted side effects of neurogenic bladder. These experiments will demonstrate the neurophysiologic response of acute stimulation through urodynamic test, and will also provide increased evidence for future clinical trials through proof of lessened bladder pressures - an important cause of vesico-ureteral reflux and renal injury.

There is a potentially larger population of persons with incomplete SCI than complete SCI who retain sensation in the pelvis who could gain benefit from dermatome stimulation. To examine the outcomes following incomplete SCI (in persons who retain sensation in the pelvis), investigators will test dermatome stimulation to determine the tolerable and effective electrical stimulation parameters in persons that have some degree of preserved motor or sensory function through the lowest sacral spinal cord segments. Investigators will acutely measure the effects of dermatome stimulation on bladder pressure and hyper-reflexic bladder contractions during bladder filling. Investigators hypothesize that dermatome stimulation will increase bladder capacity at stimulus amplitudes that are acutely tolerable to subjects with incomplete SCI. It will determine the feasibility of a non-invasive screening procedure to identify potential candidates for future device implantation, thereby providing a pathway for translation of the technology to implantation.

This project will improve the understanding of the neurophysiology of afferent-mediated neural pathways that affect bladder function, and translate recent advances discovered in animal and human studies into clinical research and treatment. The ability to void safely and effectively by electrical stimulation without cutting sacral nerves or the external urethral sphincter would be a major advance. A socially acceptable, predictable and reliable device for reducing incontinence would be widely used and improve quality of life.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Non-invasive Nerve Stimulation for Inhibition of Bladder Incontinence in Spinal Cord Injured Subjects.
• Actual Study Start Date: Oct 21, 2016
• Actual Primary Completion Date: Dec 2, 2016
• Anticipated Study Completion Date: Aug 1, 2021

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Dermatome stimulation Check the effect of improving the function of bladder storage and bladder capacity before and after dermatome stimulation.

Device: Dermatome stimulation; Dermatome (S2-S4) stimulation is aimed at improving the function of bladder storage and bladder capacity. A total of 8 serial cystometrograms will be performed: 2 control fills, followed by 4 fills with stimulation, followed by 2 control fills. The minimum (or threshold) stimulation amplitude (T) necessary to elicit the genito-anal reflex was first determined for each subject. Subsequently, each subject received a randomized sequence of cystometric fill trials with and without continuous dermatome stimulation. The dermatome stimulation was randomly stimulated at stimulation amplitudes of 1, 2, 3, and 4 T.

Outcome Measures

Primary Outcome Measures

1. The Changes of Bladder Capacity (mL) by Using Urodynamic Measurement [The outcome measure will be assessed in day 1.]

   Investigator will verify that S2-S4 dermatome nerve stimulation is acutely effective at reducing hyper-reflexic bladder activity during bladder filling in urodynamic measurement. All experimental trials will be completed in one day for each subject. Serial cystometrograms will be conducted by filling the bladder with saline and recording the volume in the bladder with or without concomitant nerve stimulation. A total of 8 serial cystometrograms will be performed: 2 control fills, followed by 4 fills with stimulation, followed by 2 control fills. Stimulation threshold will be randomly given (1-4 folds of stimulation threshold). Data from each of 4 stimulation fills per threshold or a total of 4 control fills were averaged. The averaged values are presented per Arm/Group below. The interval between every fill is 20-40 min. Investigator will compare the difference of bladder capacity (mL) between giving-control fill and fill with stimulation through statistical analysis.

Secondary Outcome Measures

1. The Changes of Bladder Pressure (cmH2O) During Urodynamic Measurement [The outcome measure will be assessed in day 1.]

   Investigator will verify that S2-S4 dermatome nerve stimulation is acutely effective at reducing hyper-reflexic bladder activity during bladder filling in urodynamic measurement. All experimental trials will be completed in one day for each subject. Serial cystometrograms will be conducted by filling the bladder with saline and recording the pressure in the bladder with or without concomitant nerve stimulation. A total of 8 serial cystometrograms will be performed: 2 control fills, followed by 4 fills with stimulation, followed by 2 control fills. Stimulation threshold will be randomly given (1-4 folds of stimulation threshold). The interval between every fill is 20-40 min. Investigator will compare the difference of bladder capacity (mL) between giving-control fill and fill with stimulation through statistical analysis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Suprasacral SCI

• Neurologically stable

• Skeletally mature, over 18 years of age.

• At least six (6) months post SCI

• Able to understand and comply with study requirements

• Able to understand and give informed consent.

Exclusion Criteria:

• Active sepsis

• Open wound or pressure sores on cutaneous area

• Significant trauma, erosion or stricture of the urethra

• Pregnancy

• Individuals who can not speak.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Taipei Medical University

Investigators

• Principal Investigator: Chih-Wei Peng, Ph.D., Professor, School of Biomedical Engineering, Taipei Medical University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 29, 2020

More Information

Publications

None provided.

• Responsible Party: Taipei Medical University
• ClinicalTrials.gov Identifier: NCT03877432
• Other Study ID Numbers: N201605025
• First Posted: Mar 15, 2019
• Last Update Posted: Jan 20, 2021
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Spinal Cord Injuries; Enuresis; Urinary Incontinence

Study Results

Participant Flow

Arm/Group Title	Dermatome Stimulation
Arm/Group Description	Check the effect of improving the function of bladder storage and bladder capacity before and after dermatome stimulation. Dermatome stimulation: Dermatome (S2-S4) stimulation is aimed at improving the function of bladder storage and bladder capacity. A total of 8 serial cystometrograms will be performed: 2 control fills, followed by 4 fills with stimulation, followed by 2 control fills. The minimum (or threshold) stimulation amplitude (T) necessary to elicit the genito-anal reflex was first determined for each subject. Subsequently, each subject received a randomized sequence of cystometric fill trials with and without continuous dermatome stimulation. The dermatome stimulation was randomly stimulated at stimulation amplitudes of 1, 2, 3, and 4 T.
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Dermatome Stimulation
Arm/Group Description	Check the effect of improving the function of bladder storage and bladder capacity before and after dermatome stimulation. Dermatome stimulation: Dermatome (S2-S4) stimulation is aimed at improving the function of bladder storage and bladder capacity. A total of 8 serial cystometrograms will be performed: 2 control fills, followed by 4 fills with stimulation, followed by 2 control fills. The minimum (or threshold) stimulation amplitude (T) necessary to elicit the genito-anal reflex was first determined for each subject. Subsequently, each subject received a randomized sequence of cystometric fill trials with and without continuous dermatome stimulation. The dermatome stimulation was randomly stimulated at stimulation amplitudes of 1, 2, 3, and 4 T.
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	10 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	10 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	10 100%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
Taiwan	10 100%

Outcome Measures

1. Primary Outcome

Title	The Changes of Bladder Capacity (mL) by Using Urodynamic Measurement
Description	Investigator will verify that S2-S4 dermatome nerve stimulation is acutely effective at reducing hyper-reflexic bladder activity during bladder filling in urodynamic measurement. All experimental trials will be completed in one day for each subject. Serial cystometrograms will be conducted by filling the bladder with saline and recording the volume in the bladder with or without concomitant nerve stimulation. A total of 8 serial cystometrograms will be performed: 2 control fills, followed by 4 fills with stimulation, followed by 2 control fills. Stimulation threshold will be randomly given (1-4 folds of stimulation threshold). Data from each of 4 stimulation fills per threshold or a total of 4 control fills were averaged. The averaged values are presented per Arm/Group below. The interval between every fill is 20-40 min. Investigator will compare the difference of bladder capacity (mL) between giving-control fill and fill with stimulation through statistical analysis.
Time Frame	The outcome measure will be assessed in day 1.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	1T (Threshold)	2T (Threshold)	3T (Threshold)	4T (Threshold)
Arm/Group Description	Subjects first received a control fill without genital nerve stimulation (GNS) to determine their bladder capacity (baseline).	Subjects received 1 fold of stimulation threshold (1T) amplitude while cystometrogram performed.	Subjects received 2 folds of stimulation threshold (2T) amplitude while cystometrogram performed.	Subjects received 3 folds of stimulation threshold (3T) amplitude while cystometrogram performed.	Subjects received 4 folds of stimulation threshold (4T) amplitude while cystometrogram performed.
Measure Participants	8	8	8	8	4
Mean (Standard Deviation) [ml]	253 (112)	346 (116)	332 (137)	390 (157)	401 (134)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, 1T (Threshold)
	Comments	All data were presented as means ± standard deviations (SDs). Analysis of variance (ANOVA) was used to compare the effects of 1T stimulation amplitude changes on bladder capacity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Control, 2T (Threshold)
	Comments	All data were presented as means ± standard deviations (SDs). Analysis of variance (ANOVA) was used to compare the effects of 2T stimulation amplitude changes on bladder capacity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.017
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Control, 3T (Threshold)
	Comments	All data were presented as means ± standard deviations (SDs). Analysis of variance (ANOVA) was used to compare the effects of 3T stimulation amplitude changes on bladder capacity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Control, 4T (Threshold)
	Comments	All data were presented as means ± standard deviations (SDs). Analysis of variance (ANOVA) was used to compare the effects of 4T stimulation amplitude changes on bladder capacity.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	ANOVA
	Comments

2. Secondary Outcome

Title	The Changes of Bladder Pressure (cmH2O) During Urodynamic Measurement
Description	Investigator will verify that S2-S4 dermatome nerve stimulation is acutely effective at reducing hyper-reflexic bladder activity during bladder filling in urodynamic measurement. All experimental trials will be completed in one day for each subject. Serial cystometrograms will be conducted by filling the bladder with saline and recording the pressure in the bladder with or without concomitant nerve stimulation. A total of 8 serial cystometrograms will be performed: 2 control fills, followed by 4 fills with stimulation, followed by 2 control fills. Stimulation threshold will be randomly given (1-4 folds of stimulation threshold). The interval between every fill is 20-40 min. Investigator will compare the difference of bladder capacity (mL) between giving-control fill and fill with stimulation through statistical analysis.
Time Frame	The outcome measure will be assessed in day 1.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	3 months
Arm/Group Title	Dermatome Stimulation
Arm/Group Description	Check the effect of improving the function of bladder storage and bladder capacity before and after dermatome stimulation. Dermatome stimulation: Dermatome (S2-S4) stimulation is aimed at improving the function of bladder storage and bladder capacity. A total of 8 serial cystometrograms will be performed: 2 control fills, followed by 4 fills with stimulation, followed by 2 control fills. The minimum (or threshold) stimulation amplitude (T) necessary to elicit the genito-anal reflex was first determined for each subject. Subsequently, each subject received a randomized sequence of cystometric fill trials with and without continuous dermatome stimulation. The dermatome stimulation was randomly stimulated at stimulation amplitudes of 1, 2, 3, and 4 T.
All Cause Mortality
	Dermatome Stimulation
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Serious Adverse Events
	Dermatome Stimulation
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Other (Not Including Serious) Adverse Events
	Dermatome Stimulation
	Affected / at Risk (%)	# Events
Total	0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.