RestoreSensor Study

• Sponsor: MedtronicNeuro (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01106404
• Collaborator: (none)
• Enrollment: 79
• Locations: 10
• Arms: 2
• Duration (Months): 9
• Patients Per Site: 7.9
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The purpose of the study is to gather clinical information on subjects' experiences with and without the use of the new feature of the RestoreSensor implantable neurostimulator (INS).

Condition or Disease	Intervention/Treatment	Phase
Chronic Pain	Device: RestoreSensor Neurostimulation System	N/A

Detailed Description

This study is a multi-center, prospective, open-label, randomized, crossover study that is designed to gather clinical information on subjects' experiences with the use of the new feature of the RestoreSensor implantable neurostimulator. Current spinal cord stimulators for chronic intractable pain stimulate targeted nerves along the spine using electrical impulses. The stimulation interferes with the transmission of pain signals to the brain replacing painful sensations with a tingling sensation called paresthesia. Variation in the intensity of neurostimulation with body position is a challenge for some patients implanted with conventional spinal cord stimulation systems because positional changes may result in overstimulation or understimulation. Patients need to manually adjust their stimulation using the patient programmer to maintain their comfort level during position changes. The AdaptiveStim feature of the RestoreSensor neurostimulator was developed to address this challenge by improving pain relief and/or convenience relative to manual programming adjustments.

Study Design

• Study Type: Interventional
• Actual Enrollment: 79 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: RestoreSensor Study
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Other: 6-week AdaptiveStim followed by 6-week manual programming	Device: RestoreSensor Neurostimulation System; Adjustments to stimulation settings are automatic when the AdaptiveStim feature of the device is turned "ON" and manual when the AdaptiveStim feature of the device is turned "OFF".
Other: 6-week manual followed by 6-week AdaptiveStim programming	Device: RestoreSensor Neurostimulation System; Adjustments to stimulation settings are automatic when the AdaptiveStim feature of the device is turned "ON" and manual when the AdaptiveStim feature of the device is turned "OFF".

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects With Improved Pain Relief and/or Convenience During the AdaptiveStim Programming Arm Relative to the Manual Programming Arm [16 weeks post-implant]

   After subjects experienced both AdaptiveStim and manual programming at 16 weeks post-implant, subjects were asked to compare pain relief and convenience when they had AdaptiveStim ON to AdaptiveStim OFF in two separate domains using two 5-point Likert scales. The outcome measure for the primary objective is the percentage of subjects who report improved pain relief with no loss of convenience or improved convenience with no loss of pain relief during the AdaptiveStim programming arm relative to the manual programming arm. These subjects were considered successful for the primary objective.

Secondary Outcome Measures

1. Percentage of Subjects With Worsened Pain Relief When Using AdaptiveStim Compared to Manual Programming [16 weeks post-implant]

   The pain relief question was a 5-point Likert scale question comparing pain relief when using AdaptiveStim programming relative to manual programming after subjects finished both programming periods. The choices were much worse pain relief with AdaptiveStim, somewhat worse pain relief with AdaptiveStim, no difference in pain relief, somewhat better pain relief with AdaptiveStim, and much better pain relief with AdaptiveStim. Subjects who had worsening pain relief were defined as subjects who responded "much worse pain relief with AdaptiveStim" or "somewhat worse pain relief with AdaptiveStim".

2. Manual Adjustments Presented as Button Presses [Baseline, 10 weeks and 16 weeks post-implant]

   The number of individual adjustments, ie, button presses, were recorded automatically in the patient programmer, which was specifically designed for this study. The number of button presses per day for manual patient programmer adjustments during the manual programming arm and the AdaptiveStim programming arm of the study were compared.

3. NPRS Scores From Baseline to Follow-up Visits at 10 Weeks and 16 Weeks Post-implant [Baseline, 10 weeks and 16 weeks post-implant]

   The 11-point (ie, 0-10) numeric rating scale of pain intensity (NPRS) was used to assess the overall pain at baseline and follow-up visits. In the pain diary, subjects were presented a numeric scale with numbers from 0 to 10, with 0 meaning "No pain" and 10 meaning "Pain as bad as you can imagine," accompanied by the instructions "Please rate your pain by indicating the number that best describes your pain on average in the last 24 hours." The subjects were asked to complete a diary for 7 consecutive days before implant, 10 weeks, and 16 weeks post-implant visits.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Meets the indications as an appropriate surgical candidate (after successful SCS screening trial) for implant of a neurostimulation system for spinal cord stimulation (SCS) treatment of trunk and/or limb pain, per labeled indications

• 18 years of age or older

• Willing and able to attend visits and comply with the study protocol

• Capable of using the patient programmer and recharging the neurostimulator (INS), able to read and answer questionnaires in English, without assistance of a caregiver

• Males and non-pregnant females

Exclusion Criteria:

• Has had a prior implantable SCS neurostimulation system

• Currently enrolled, or plans to enroll in another investigational device or drug trial during the study

• Has unresolved legal issues related to their pain condition for which they would be receiving neurostimulation

• Requires cervical placement of leads.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Huntsville	Alabama	United States	35801
2		Oceanside	California	United States	92056
3		Edina	Minnesota	United States	55435
4		Las Vegas	Nevada	United States	89149
5		Voorhees	New Jersey	United States	08043
6		Eugene	Oregon	United States	97401
7		Dallas	Texas	United States	75237
8		San Antonio	Texas	United States	78229
9		San Antonio	Texas	United States	78258
10		Salt Lake City	Utah	United States	84106

Sponsors and Collaborators

• MedtronicNeuro

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: MedtronicNeuro
• ClinicalTrials.gov Identifier: NCT01106404
• Other Study ID Numbers: 1651
• First Posted: Apr 19, 2010
• Last Update Posted: Aug 30, 2012
• Last Verified: Aug 1, 2012

• Additional relevant MeSH terms: Chronic Pain

Study Results

Participant Flow

Recruitment Details	The sponsor activated 10 study centers after the study protocol was approved by FDA in March 2010. The overall recruitment for study subjects lasted less than 5 months, with the first enrollment on April 20, 2010, and last enrollment on September 3, 2010.
Pre-assignment Detail	Among the 79 subjects enrolled into the study, there were 3 subjects discontinued prior to implantation. The reasons for discontinuations were withdrawal of consent (n = 2) and eligibility criteria not met (n = 1). A total of 76 subjects were implanted and randomized at 4 weeks post implant.

Arm/Group Title	6-week AdaptiveStim Followed by 6-week Manual Programming	6-week Manual Followed by 6-week AdaptiveStim Programming
Arm/Group Description	Subjects received AdaptiveStim programming for 6 weeks, followed by manual programming for 6 weeks.	Subjects received manual programming for 6 weeks, followed by AdaptiveStim programming for 6 weeks.
Period Title: Period I (First 6 Weeks)
STARTED	36	40
COMPLETED	33	38
NOT COMPLETED	3	2
Period Title: Period I (First 6 Weeks)
STARTED	33	38
COMPLETED	33	38
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	6-week AdaptiveStim Followed by 6-week Manual Programming	6-week Manual Followed by 6-week AdaptiveStim Programming	Total
Arm/Group Description	Subjects received AdaptiveStim programming for 6 weeks, followed by manual programming for 6 weeks.	Subjects received manual programming for 6 weeks, followed by AdaptiveStim programming for 6 weeks.	Total of all reporting groups
Overall Participants	36	40	76
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	31 86.1%	30 75%	61 80.3%
>=65 years	5 13.9%	10 25%	15 19.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.5 (13.0)	53.1 (14.1)	52.8 (13.5)
Sex: Female, Male (Count of Participants)
Female	18 50%	27 67.5%	45 59.2%
Male	18 50%	13 32.5%	31 40.8%
Region of Enrollment (participants) [Number]
United States	36 100%	40 100%	76 100%
average Numeric Pain Rating Scale (NPRS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	6.26 (1.48)	5.88 (2.15)	6.06 (1.86)
worst Numeric Pain Rating Scale (NPRS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	7.60 (1.15)	7.60 (1.63)	7.60 (1.41)

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects With Improved Pain Relief and/or Convenience During the AdaptiveStim Programming Arm Relative to the Manual Programming Arm
Description	After subjects experienced both AdaptiveStim and manual programming at 16 weeks post-implant, subjects were asked to compare pain relief and convenience when they had AdaptiveStim ON to AdaptiveStim OFF in two separate domains using two 5-point Likert scales. The outcome measure for the primary objective is the percentage of subjects who report improved pain relief with no loss of convenience or improved convenience with no loss of pain relief during the AdaptiveStim programming arm relative to the manual programming arm. These subjects were considered successful for the primary objective.
Time Frame	16 weeks post-implant

Outcome Measure Data

Analysis Population Description

The ITT analysis included 74 subjects; 2 randomized subjects, who discontinued early due to infections, were excluded per protocol. The 3 other subjects who discontinued early were included in ITT analysis and imputed as failures for the primary objective. No imputation method was used for 71 subjects included in the completed case analysis.

Arm/Group Title	6-week AdaptiveStim Followed by 6-week Manual Programming	6-week Manual Followed by 6-week AdaptiveStim Programming
Arm/Group Description	Subjects received AdaptiveStim programming for 6 weeks, followed by manual programming for 6 weeks.	Subjects received manual programming for 6 weeks, followed by AdaptiveStim programming for 6 weeks.
Measure Participants	34	40
Intent-to-treat analysis (n = 34, 40)	91.2 253.3%	82.5 206.3%
Completed case analysis (n = 33, 38)	93.9 260.8%	86.8 217%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	6-week AdaptiveStim Followed by 6-week Manual Programming, 6-week Manual Followed by 6-week AdaptiveStim Programming
	Comments	ITT analysis: Hypothesis: The percentage of subjects who succeed must be greater than 25%. H0: p ≤ 0.25 HA: p > 0.25
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	binomial proportion
	Estimated Value	0.865
	Confidence Interval	(1-Sided) 97.5%; 0.765 to
	Parameter Dispersion	Type: Value:
	Estimation Comments	In this ITT analysis, the combined percentage of subjects with improved pain relief and/or convenience during the AdaptiveStim programming relative to the manual programming in both groups was reported.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	6-week AdaptiveStim Followed by 6-week Manual Programming, 6-week Manual Followed by 6-week AdaptiveStim Programming
	Comments	Completed case analysis
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	binomial proportion
	Estimated Value	0.901
	Confidence Interval	(1-Sided) 97.5%; 0.807 to
	Parameter Dispersion	Type: Value:
	Estimation Comments	In this completed case analysis, the combined percentage of subjects with improved pain relief and/or convenience during the AdaptiveStim programming relative to the manual programming in both groups was reported.

2. Secondary Outcome

Title	Percentage of Subjects With Worsened Pain Relief When Using AdaptiveStim Compared to Manual Programming
Description	The pain relief question was a 5-point Likert scale question comparing pain relief when using AdaptiveStim programming relative to manual programming after subjects finished both programming periods. The choices were much worse pain relief with AdaptiveStim, somewhat worse pain relief with AdaptiveStim, no difference in pain relief, somewhat better pain relief with AdaptiveStim, and much better pain relief with AdaptiveStim. Subjects who had worsening pain relief were defined as subjects who responded "much worse pain relief with AdaptiveStim" or "somewhat worse pain relief with AdaptiveStim".
Time Frame	16 weeks post-implant

Outcome Measure Data

Analysis Population Description

A total of 71 subjects with completed data were included in this analysis.

Arm/Group Title	6-week AdaptiveStim Followed by 6-week Manual Programming	6-week Manual Followed by 6-week AdaptiveStime Programming
Arm/Group Description	Subjects received AdaptiveStim programming for 6 weeks, followed by manual programming for 6 weeks.	Subjects received manual programming for 6 weeks, followed by AdaptiveStim programming for 6 weeks.
Measure Participants	33	38
Number [percentage of participants]	0 0%	5.3 13.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	6-week AdaptiveStim Followed by 6-week Manual Programming, 6-week Manual Followed by 6-week AdaptiveStim Programming
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	binomial proportion
	Estimated Value	0.028
	Confidence Interval	(2-Sided) 95%; 0.003 to 0.098
	Parameter Dispersion	Type: Value:
	Estimation Comments	The combined percentage of subjects with worsened pain relief was reported.

3. Secondary Outcome

Title	Manual Adjustments Presented as Button Presses
Description	The number of individual adjustments, ie, button presses, were recorded automatically in the patient programmer, which was specifically designed for this study. The number of button presses per day for manual patient programmer adjustments during the manual programming arm and the AdaptiveStim programming arm of the study were compared.
Time Frame	Baseline, 10 weeks and 16 weeks post-implant

Outcome Measure Data

Analysis Population Description

Subjects with manual adjustments data from patient programmer were included in the analysis.

Arm/Group Title	AdaptiveStim Treatment Arm	Manual Treatment Arm
Arm/Group Description	Subjects in AdaptiveStim treatment arm received programming provided by the RestoreSensor neurostimulator with AdaptiveStim ON.	Subjects in manual treatment arm received programming provided by the RestoreSensor neurostimulator with AdaptiveStim OFF.
Measure Participants	69	69
Mean (Standard Deviation) [Button presses per day]	20.9 (41.4)	35.7 (71.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	6-week AdaptiveStim Followed by 6-week Manual Programming, 6-week Manual Followed by 6-week AdaptiveStim Programming
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Wilcoxon signed rank test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	14.8
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Deviation; Value: 51.9
	Estimation Comments

4. Secondary Outcome

Title	NPRS Scores From Baseline to Follow-up Visits at 10 Weeks and 16 Weeks Post-implant
Description	The 11-point (ie, 0-10) numeric rating scale of pain intensity (NPRS) was used to assess the overall pain at baseline and follow-up visits. In the pain diary, subjects were presented a numeric scale with numbers from 0 to 10, with 0 meaning "No pain" and 10 meaning "Pain as bad as you can imagine," accompanied by the instructions "Please rate your pain by indicating the number that best describes your pain on average in the last 24 hours." The subjects were asked to complete a diary for 7 consecutive days before implant, 10 weeks, and 16 weeks post-implant visits.
Time Frame	Baseline, 10 weeks and 16 weeks post-implant

Outcome Measure Data

Analysis Population Description

69 of the 76 subjects completed pain diary for both baseline and 10 weeks. 69 of the 76 subjects completed pain diary for both baseline and 16 weeks. Since 2 datasets had 2 different pairs of data due to different subjects who completed the pain diary, baseline NPRS in two analyses varied slightly.

Arm/Group Title	NPRS at Baseline (Subject With Score at 10 Weeks Post-implant)	NPRS at 10 Weeks Post-implant	NPRS at Baseline (Subject With Score at 16 Weeks Post-implant)	NPRS at 16 Weeks Post-implant
Arm/Group Description	Included subjects with NPRS scores from both baseline and 10 weeks post-implant	Included subjects with NPRS scores from both baseline and 10 weeks post-implant	Included subjects with NPRS scores from both baseline and 16 weeks post-implant	Included subjects with NPRS scores from both baseline and 16 weeks post-implant
Measure Participants	69	69	69	69
Mean (Standard Deviation) [units on a scale]	5.99 (1.82)	4.22 (2.05)	5.90 (1.81)	4.41 (2.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	6-week AdaptiveStim Followed by 6-week Manual Programming, 6-week Manual Followed by 6-week AdaptiveStim Programming
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Wilcoxon signed rank test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.77
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Deviation; Value: 1.93
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	NPRS at Baseline (Subject With Score at 16 Weeks Post-implant), NPRS at 16 Weeks Post-implant
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	Wilcoxon signed rank test
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.50
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Standard Deviation; Value: 2.04
	Estimation Comments

Adverse Events

Time Frame	The time frame for safety reporting was from study enrollment to final visit. After implant, subjects were followed for an average duration of 16 weeks during which they experienced both manual and AdaptiveStim programming of the RestoreSensor device.
Arm/Group Title	Overall Adverse Events
Arm/Group Description	Overall adverse events were reported.
All Cause Mortality
	Overall Adverse Events
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Overall Adverse Events
	Affected / at Risk (%)	# Events
Total	8/76 (10.5%)
Cardiac disorders
Atrial fibrillation	1/76 (1.3%)	1
Gastrointestinal disorders
Gastritis	1/76 (1.3%)	1
Infections and infestations
Gastroenteritis	1/76 (1.3%)	1
Implant site infection	1/76 (1.3%)	1
Injury, poisoning and procedural complications
Fall	1/76 (1.3%)	1
Seroma	1/76 (1.3%)	1
Wound dehiscence	1/76 (1.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma	1/76 (1.3%)	1
Psychiatric disorders
Suicide attempt	1/76 (1.3%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/76 (1.3%)	1
Other (Not Including Serious) Adverse Events
	Overall Adverse Events
	Affected / at Risk (%)	# Events
Total	53/76 (69.7%)
General disorders
Undesirable change in stimulation	21/76 (27.6%)	25
Change in sensation of stimulation	4/76 (5.3%)	5
Pain	9/76 (11.8%)	10
Implant site irritation	4/76 (5.3%)	4
Infections and infestations
Nasopharyngitis	7/76 (9.2%)	7
Influenza	4/76 (5.3%)	4
Musculoskeletal and connective tissue disorders
Back pain	12/76 (15.8%)	17
Muscle spasms	10/76 (13.2%)	11
Pain in extremity	5/76 (6.6%)	5
Arthralgia	4/76 (5.3%)	4
Nervous system disorders
Paraesthesia	4/76 (5.3%)	4
Psychiatric disorders
Depression	5/76 (6.6%)	5
Insomnia	4/76 (5.3%)	4
Skin and subcutaneous tissue disorders
Pruritus	5/76 (6.6%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.