InterStim® Sacral Nerve Modulation Cycling Study

• Sponsor: MedtronicNeuro (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01957137
• Collaborator: (none)
• Enrollment: 30
• Locations: 3
• Arms: 5
• Duration (Months): 26
• Patients Per Site: 10
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The study will assess the effects of different InterStim cycling settings on urinary urge incontinence.

Condition or Disease	Intervention/Treatment	Phase
Urinary Urge Incontinence	Device: InterStim® (Device Programming)	N/A

Detailed Description

This feasibility study will assess the following outcomes:

• Voiding diaries

• Patient reported assessments of response or satisfaction

• Adverse events

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: InterStim® Sacral Nerve Modulation Cycling Study
• Study Start Date: Sep 1, 2013
• Actual Primary Completion Date: Nov 1, 2015
• Actual Study Completion Date: Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Other: Continuous The device parameter will be continuous.	Device: InterStim® (Device Programming)
Other: Cycling Parameter #1 The device parameter will be cyclic program #1.	Device: InterStim® (Device Programming)
Other: Cycling Parameter #2 The device parameter will be cyclic program #2.	Device: InterStim® (Device Programming)
Other: Cycling Parameter #3 The device parameter will be cyclic program #3.	Device: InterStim® (Device Programming)
Other: No Stimulation Following the randomized portion of the study, an assessment was conducted to estimate the effect of a month of no stimulation on incontinence.	Device: InterStim® (Device Programming)

Outcome Measures

Primary Outcome Measures

1. Number of Urinary Urge Incontinent (UUI) Episodes Per Day - Randomized Portion [4 weeks]

   Urinary urge incontinent episodes were collected through a diary on daily basis for approximately 4 weeks when subjects were under each cycling setting. Only the last 7-day diaries were used for the analysis. The first 3 weeks were used as an adjustment period.

Secondary Outcome Measures

1. Degree of Urgency - Randomized Portion [4 week]

   Each UUI episode was rated on following scales: 0=None, 1=Mild, 2=Moderate, 3=Severe, which were collected through a diary on daily basis for approximately 4 weeks when subjects were under each cycling setting. The average degree of urgency per UUI episode was calculated from the last 7-day diaries were used for the analysis. The first 3 weeks were used as an adjustment period.

2. Number of Pads Used Per Day - Randomized Portion [4 weeks]

   Number of pad use were collected through a diary on daily basis for approximately 4 weeks when subjects were under each cycling setting. Only the last 7-day diaries were used for the analysis. The first 3 weeks were used as an adjustment period.

3. Global Response Assessment (GRA) - Randomized Portion [4 weeks]

   Summary statistics of GRA at different cycling settings are provided. The GRA assessed incontinence symptoms as compared to symptoms prior to subject's entry into the study. Subjects were asked how much their incontinence changed since starting the study: markedly worse, moderately worse, mildly worse, same, slightly improved, moderately improved, or markedly improved. The responses to the symptom change were categorized into three levels for the analysis: worse (markedly worse, moderately worse, mildly worse), same (same), better (slightly improved, moderately improved, or markedly improved). Percentages of subjects reported worse, same or better under each cycling setting since starting the study are presented.

4. Number of UUI Episodes Per Day - no Stimulation [4 Weeks]

   UUI episodes were collected through a diary on daily basis for approximately 4 weeks when subjects were under no stimulation. Only the last 7-day diaries were used for the analysis. The first 3 weeks were used as an adjustment period.

5. Degree of Urgency - no Stimulation [4 weeks]

   Each UUI episode was rated on following scales: 0=None, 1=Mild, 2=Moderate, 3=Severe, which were collected through a diary on daily basis for approximately 4 weeks when subjects were under no stimulation. The average degree of urgency per UUI episode was calculated from the last 7-day diaries were used for the analysis. The first 3 weeks were used as an adjustment period.

6. Number of Pads Used Per Day - no Stimulation [4 Weeks]

   Number of pad use were collected through a diary on daily basis for approximately 4 weeks when subjects were under no stimulation. Only the last 7-day diaries were used for the analysis. The first 3 weeks were used as an adjustment period.

7. Global Response Assessment - no Stimulation [4 Weeks]

   Summary of GRA under no stimulation setting is provided. The GRA assessed incontinence symptoms as compared to symptoms prior to subject's entry into the study. Subjects were asked how much their incontinence changed since starting the study: markedly worse, moderately worse, mildly worse, same, slightly improved, moderately improved, or markedly improved. The responses to the symptom change were categorized into three levels for the analysis: worse (markedly worse, moderately worse, mildly worse), same (same), better (slightly improved, moderately improved, or markedly improved).

8. Adverse Events - no Stimulation [4 Weeks]

   Summary of adverse device effects when subjects were under no stimulation is provided. Percentage of subjects experiencing any type of Adverse Device Effect under no stimulation is presented.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Implanted with either Neurostimulator Model 3023 (InterStim) or Neurostimulator Model 3058 (InterStim II) for at least 3 months

2. Implanted with tined lead models 3889 or 3093

3. Tined lead is located at S3 as determined by sensory or motor responses or x-ray or fluoroscopy

4. Currently showing some efficacy with an InterStim device but has the potential to be optimized per the opinion of the Investigator

5. Primary diagnosis before InterStim implant is urinary urge incontinence.

6. Must be willing to maintain her current regimen (dosage and frequency) of any overactive bladder (OAB) medication (anticholinergic, antimuscarinic or Myrbetriq (Mirabegron)) or tricyclic antidepression medication over the study duration, if applicable.

7. Female subject 18 years of age or older

8. Willing and able to accurately complete voiding diaries and questionnaires, attend visits (within the visit windows +7 days), and comply with the study protocol that includes maintenance of InterStim programming settings over the course of the study

9. Have had no more than one (InterStim) reprogramming at or within 28 days at or prior to randomization

10. Able to consent to participate by signing the Informed Consent Form

Exclusion Criteria:

1. History of Multiple sclerosis

2. History of Reiter's syndrome

3. History of spinal cord injury or a cerebral vascular accident (CVA)

4. History of diabetes unless the diabetes is well-controlled through diet and/or medications

5. Active symptomatic urinary tract infection (UTI)

6. Stress incontinence as the primary diagnosis

7. Urgency frequency as a primary diagnosis

8. Pelvic pain of uncertain etiology that is not associated with a voiding dysfunction or where pelvic pain is the primary diagnosis

9. Interstitial cystitis as the primary diagnosis

10. Urinary retention as the primary diagnosis

11. Treatment of urinary symptoms with botulinum toxin in the past 12 months or any plan to have botulinum toxin treatment during the study

12. Bilateral lead placement

13. Have other implantable neurostimulator, pacemaker, or defibrillator

14. Have knowledge of planned diathermy, microwave exposure, high output ultrasonic exposure, RF energy exposure, or MRI scans not included within the scanning conditions provided within the MRI Guidelines for InterStim Therapy neurostimulation systems.

15. Have an anticipated system modification within the next 5 months

16. Women who are pregnant or planning to become pregnant (women of child-bearing potential must undergo a pregnancy test, with a clear negative result, no more than 7 days prior to randomization visit)

17. Subjects who frequently use the patient programmer to change device program settings ("frequently" is defined as at least once a day and does not include shutting off the device for safety purposes)

18. Characteristics indicating a poor understanding of the study or characteristics that indicate the subject may have poor compliance with the study protocol.

19. Study site personnel will contact the Medtronic Study Manager (or designee) to determine if a potential subject who plans to enroll in an investigational device or drug trial, or is currently enrolled in an investigational device or drug trial is eligible for this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pinellas Urology, Inc.	Saint Petersburg	Florida	United States	33710
2	University of Iowa Healthcare	Iowa City	Iowa	United States	52242
3	Metro Urology	Woodbury	Minnesota	United States	55125

Sponsors and Collaborators

• MedtronicNeuro

Investigators

• Principal Investigator: Steven W Siegel, MD, Metro Urology
• Principal Investigator: Shaw Zhou, MD, Pinellas Urology, Inc.
• Principal Investigator: Karl Kreder, Jr., MD, MBA, University of Iowa Healthcare

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: MedtronicNeuro
• ClinicalTrials.gov Identifier: NCT01957137
• Other Study ID Numbers: 1670
• First Posted: Oct 8, 2013
• Last Update Posted: Dec 12, 2017
• Last Verified: Nov 1, 2017

• Keywords provided by MedtronicNeuro: Urinary; Urge; Incontinence
• Additional relevant MeSH terms: Urinary Incontinence, Urge

Study Results

Participant Flow

Recruitment Details	Thirty subjects were enrolled into the study from Sept 10, 2013 through May 22, 2015 from 3 US centers.

Arm/Group Title	All Study Participants
Arm/Group Description	Thirty subjects were randomized to 1 of 24 sequences with 4 cycling settings: 2 subjects discontinued early with 1 due to an AE, and 1 due to consent withdrawal. Twenty-eight subjects completed the randomization sequences . After that all subjects went through no stimulation for approximately 4 weeks, which was not part of randomization.
Period Title: Randomized Portion
STARTED	30
Continuous Stimulation	29
Cycling Parameter #1	30
Cycling Parameter #2	28
Cycling Parameter #3	28
COMPLETED	28
NOT COMPLETED	2
Period Title: Randomized Portion
STARTED	28
COMPLETED	28
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Subjects Who First Finished Unique Randomization Sequences
Arm/Group Description	Baseline descriptions provided were based on 24 subjects who first finished unique randomization sequences, which are those subjects included in the primary analysis of the primary outcome.
Overall Participants	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.0 (13.5)
Sex: Female, Male (Count of Participants)
Female	24 100%
Male	0 0%
Years implanted with InterStim therapy (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	2.8 (3.1)

Outcome Measures

1. Primary Outcome

Title	Number of Urinary Urge Incontinent (UUI) Episodes Per Day - Randomized Portion
Description	Urinary urge incontinent episodes were collected through a diary on daily basis for approximately 4 weeks when subjects were under each cycling setting. Only the last 7-day diaries were used for the analysis. The first 3 weeks were used as an adjustment period.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

24 subjects who first completed the unique randomization sequences were included in the analysis.

Arm/Group Title	Continuous	Cycling Parameter #1	Cycling Parameter #2	Cycling Parameter #3
Arm/Group Description	Subjects received continuous stimulation for approximately 4 weeks.	Subjects received cycling parameter #1 for approximately 4 weeks.	Subjects received cycling parameter #2 for approximately 4 weeks.	Subjects received cycling parameter #3 for approximately 4 weeks.
Measure Participants	24	24	24	24
Mean (Standard Deviation) [Number of UUI episodes/ Day]	1.64 (1.40)	1.82 (1.97)	1.44 (1.20)	1.76 (1.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Continuous, Cycling Parameter #1, Cycling Parameter #2, Cycling Parameter #3
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3773
	Comments
	Method	Mixed Models Analysis
	Comments	The final model included cycling, period and the interaction between cycling and period.

2. Secondary Outcome

Title	Degree of Urgency - Randomized Portion
Description	Each UUI episode was rated on following scales: 0=None, 1=Mild, 2=Moderate, 3=Severe, which were collected through a diary on daily basis for approximately 4 weeks when subjects were under each cycling setting. The average degree of urgency per UUI episode was calculated from the last 7-day diaries were used for the analysis. The first 3 weeks were used as an adjustment period.
Time Frame	4 week

Outcome Measure Data

Analysis Population Description

24 subjects who first completed unique randomization sequences were included in the analysis.

Arm/Group Title	Continuous	Cycling Parameter #1	Cycling Parameter #2	Cycling Parameter #3
Arm/Group Description	Subjects received continuous stimulation for approximately 4 weeks.	Subjects received cycling parameter #1 for approximately 4 weeks.	Subjects received cycling parameter #2 for approximately 4 weeks.	Subjects received cycling parameter #3 for approximately 4 weeks.
Measure Participants	24	24	24	24
Least Squares Mean (95% Confidence Interval) [units on a scale]	1.83	1.80	1.54	1.65

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Continuous, Cycling Parameter #1, Cycling Parameter #2, Cycling Parameter #3
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2396
	Comments
	Method	Mixed Models Analysis
	Comments	The final model included cycling and period.

3. Secondary Outcome

Title	Number of Pads Used Per Day - Randomized Portion
Description	Number of pad use were collected through a diary on daily basis for approximately 4 weeks when subjects were under each cycling setting. Only the last 7-day diaries were used for the analysis. The first 3 weeks were used as an adjustment period.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

24 subjects who first completed unique randomization sequences were included in the analysis.

Arm/Group Title	Continuous	Cycling Parameter #1	Cycling Parameter #2	Cycling Parameter #3
Arm/Group Description	Subjects received continuous stimulation for approximately 4 weeks.	Subjects received cycling parameter #1 for approximately 4 weeks.	Subjects received cycling parameter #2 for approximately 4 weeks.	Subjects received cycling parameter #3 for approximately 4 weeks.
Measure Participants	24	24	24	24
Least Squares Mean (95% Confidence Interval) [Pads per day]	1.10	1.16	1.17	1.20

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Continuous, Cycling Parameter #1, Cycling Parameter #2, Cycling Parameter #3
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8874
	Comments
	Method	Mixed Models Analysis
	Comments	The final model included cycling and period.

4. Secondary Outcome

Title	Global Response Assessment (GRA) - Randomized Portion
Description	Summary statistics of GRA at different cycling settings are provided. The GRA assessed incontinence symptoms as compared to symptoms prior to subject's entry into the study. Subjects were asked how much their incontinence changed since starting the study: markedly worse, moderately worse, mildly worse, same, slightly improved, moderately improved, or markedly improved. The responses to the symptom change were categorized into three levels for the analysis: worse (markedly worse, moderately worse, mildly worse), same (same), better (slightly improved, moderately improved, or markedly improved). Percentages of subjects reported worse, same or better under each cycling setting since starting the study are presented.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

24 subjects who first completed unique randomization sequences were included in the analysis.

Arm/Group Title	Continuous	Cycling Parameter #1	Cycling Parameter #2	Cycling Parameter #3
Arm/Group Description	Subjects received continuous stimulation for approximately 4 weeks.	Subjects received cycling parameter #1 for approximately 4 weeks.	Subjects received cycling parameter #2 for approximately 4 weeks.	Subjects received cycling parameter #3 for approximately 4 weeks.
Measure Participants	24	24	24	24
Better	29	38	54	42
Same	25	21	17	38
Worse	46	42	29	21

5. Secondary Outcome

Title	Number of UUI Episodes Per Day - no Stimulation
Description	UUI episodes were collected through a diary on daily basis for approximately 4 weeks when subjects were under no stimulation. Only the last 7-day diaries were used for the analysis. The first 3 weeks were used as an adjustment period.
Time Frame	4 Weeks

Outcome Measure Data

Analysis Population Description

28 subjects who received no stimulation were included in the analysis.

Arm/Group Title	No Stimulation
Arm/Group Description	Following the randomized portion of the study, all subjects went through no stimulation for approximately 4 weeks.
Measure Participants	28
Mean (Standard Deviation) [Number of UUI episodes/ Day]	1.97 (2.04)

6. Secondary Outcome

Title	Degree of Urgency - no Stimulation
Description	Each UUI episode was rated on following scales: 0=None, 1=Mild, 2=Moderate, 3=Severe, which were collected through a diary on daily basis for approximately 4 weeks when subjects were under no stimulation. The average degree of urgency per UUI episode was calculated from the last 7-day diaries were used for the analysis. The first 3 weeks were used as an adjustment period.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

28 subjects who received no stimulation were included in the analysis.

Arm/Group Title	No Stimulation
Arm/Group Description	Following the randomized portion of the study, all subjects went through no stimulation for approximately 4 weeks.
Measure Participants	28
Mean (Standard Deviation) [units on a scale]	1.77 (0.64)

7. Secondary Outcome

Title	Number of Pads Used Per Day - no Stimulation
Description	Number of pad use were collected through a diary on daily basis for approximately 4 weeks when subjects were under no stimulation. Only the last 7-day diaries were used for the analysis. The first 3 weeks were used as an adjustment period.
Time Frame	4 Weeks

Outcome Measure Data

Analysis Population Description

28 subjects who received no stimulation were included in the analysis.

Arm/Group Title	No Stimulation
Arm/Group Description	Following the randomized portion of the study, all subjects went through no stimulation for approximately 4 weeks.
Measure Participants	28
Mean (Standard Deviation) [Pad use / day]	1.23 (1.22)

8. Secondary Outcome

Title	Global Response Assessment - no Stimulation
Description	Summary of GRA under no stimulation setting is provided. The GRA assessed incontinence symptoms as compared to symptoms prior to subject's entry into the study. Subjects were asked how much their incontinence changed since starting the study: markedly worse, moderately worse, mildly worse, same, slightly improved, moderately improved, or markedly improved. The responses to the symptom change were categorized into three levels for the analysis: worse (markedly worse, moderately worse, mildly worse), same (same), better (slightly improved, moderately improved, or markedly improved).
Time Frame	4 Weeks

Outcome Measure Data

Analysis Population Description

28 subjects who received no stimulation were included in the analysis.

Arm/Group Title	No Stimulation
Arm/Group Description	Following the randomized portion of the study, all subjects went through no stimulation for approximately 4 weeks.
Measure Participants	28
Better	43
Same	21
Worse	36

9. Secondary Outcome

Title	Adverse Events - no Stimulation
Description	Summary of adverse device effects when subjects were under no stimulation is provided. Percentage of subjects experiencing any type of Adverse Device Effect under no stimulation is presented.
Time Frame	4 Weeks

Outcome Measure Data

Analysis Population Description

28 subjects who received no stimulation were included in the analysis.

Arm/Group Title	No Stimulation
Arm/Group Description	Following the randomized portion of the study, all subjects went through no stimulation for approximately 4 weeks.
Measure Participants	28
Number [Percent of Subjects]	10.7

Adverse Events

Time Frame	4 Weeks per period, a total of 4 periods in randomization portion. After randomized portion, each subject was under no stimulation for a period of 4 weeks, which was not part of the randomization.
Arm/Group Title	Continuous		Cycling Parameter #1		Cycling Parameter #2		Cycling Parameter #3		No Stimulation
Arm/Group Description	Subjects received continuous stimulation for approximately 4 weeks.		Subjects received Cycling Parameter #1 for approximately 4 weeks.		Subjects received Cycling Parameter #2 for approximately 4 weeks.		Subjects received Cycling Parameter #3 for approximately 4 weeks.		Subjects received no stimulation for approximately 4 weeks.
All Cause Mortality
	Continuous		Cycling Parameter #1		Cycling Parameter #2		Cycling Parameter #3		No Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Continuous		Cycling Parameter #1		Cycling Parameter #2		Cycling Parameter #3		No Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/30 (0%)		0/28 (0%)		0/28 (0%)		0/28 (0%)
Other (Not Including Serious) Adverse Events
	Continuous		Cycling Parameter #1		Cycling Parameter #2		Cycling Parameter #3		No Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/29 (3.4%)		4/30 (13.3%)		4/28 (14.3%)		4/28 (14.3%)		0/28 (0%)
Surgical and medical procedures
Device stimulation issue	1/29 (3.4%)	1	4/30 (13.3%)	4	4/28 (14.3%)	4	4/28 (14.3%)	4	0/28 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.