Chronic Pain
Conditions
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).
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.
Interventions
DEVICERestoreSensor 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.
Sponsors
MedtronicNeuro
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
United States
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 details
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.
Participants by arm
| Arm | Count |
|---|---|
| 6-week AdaptiveStim Followed by 6-week Manual Programming Subjects received AdaptiveStim programming for 6 weeks, followed by manual programming for 6 weeks. | 36 |
| 6-week Manual Followed by 6-week AdaptiveStim Programming Subjects received manual programming for 6 weeks, followed by AdaptiveStim programming for 6 weeks. | 40 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period I (First 6 Weeks) | Adverse Event | 2 | 0 |
| Period I (First 6 Weeks) | Lack of Efficacy | 0 | 1 |
| Period I (First 6 Weeks) | Lost to Follow-up | 0 | 1 |
| Period I (First 6 Weeks) | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | 6-week Manual Followed by 6-week AdaptiveStim Programming | Total | 6-week AdaptiveStim Followed by 6-week Manual Programming |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 15 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 61 Participants | 31 Participants |
| Age Continuous | 53.1 years STANDARD_DEVIATION 14.1 | 52.8 years STANDARD_DEVIATION 13.5 | 52.5 years STANDARD_DEVIATION 13 |
| average Numeric Pain Rating Scale (NPRS) | 5.88 units on a scale STANDARD_DEVIATION 2.15 | 6.06 units on a scale STANDARD_DEVIATION 1.86 | 6.26 units on a scale STANDARD_DEVIATION 1.48 |
| Region of Enrollment United States | 40 participants | 76 participants | 36 participants |
| Sex: Female, Male Female | 27 Participants | 45 Participants | 18 Participants |
| Sex: Female, Male Male | 13 Participants | 31 Participants | 18 Participants |
| worst Numeric Pain Rating Scale (NPRS) | 7.60 units on a scale STANDARD_DEVIATION 1.63 | 7.60 units on a scale STANDARD_DEVIATION 1.41 | 7.60 units on a scale STANDARD_DEVIATION 1.15 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 53 / 76 |
| serious Total, serious adverse events | 8 / 76 |
Outcome results
Primary
Percentage of Subjects With Improved Pain Relief and/or Convenience During the AdaptiveStim Programming Arm Relative to the Manual Programming Arm
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 6-week AdaptiveStim Followed by 6-week Manual Programming | Percentage of Subjects With Improved Pain Relief and/or Convenience During the AdaptiveStim Programming Arm Relative to the Manual Programming Arm | Intent-to-treat analysis (n = 34, 40) | 91.2 percentage of participants |
| 6-week AdaptiveStim Followed by 6-week Manual Programming | Percentage of Subjects With Improved Pain Relief and/or Convenience During the AdaptiveStim Programming Arm Relative to the Manual Programming Arm | Completed case analysis (n = 33, 38) | 93.9 percentage of participants |
| 6-week Manual Followed by 6-week AdaptiveStim Programming | Percentage of Subjects With Improved Pain Relief and/or Convenience During the AdaptiveStim Programming Arm Relative to the Manual Programming Arm | Intent-to-treat analysis (n = 34, 40) | 82.5 percentage of participants |
| 6-week Manual Followed by 6-week AdaptiveStim Programming | Percentage of Subjects With Improved Pain Relief and/or Convenience During the AdaptiveStim Programming Arm Relative to the Manual Programming Arm | Completed case analysis (n = 33, 38) | 86.8 percentage of participants |
Comparison: ITT analysis:~Hypothesis: The percentage of subjects who succeed must be greater than 25%. H0: p ≤ 0.25 HA: p \> 0.25p-value: <0.001Fisher Exact
Comparison: Completed case analysisp-value: <0.001Fisher Exact
Secondary
Manual Adjustments Presented as Button Presses
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
Population: Subjects with manual adjustments data from patient programmer were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 6-week AdaptiveStim Followed by 6-week Manual Programming | Manual Adjustments Presented as Button Presses | 20.9 Button presses per day | Standard Deviation 41.4 |
| 6-week Manual Followed by 6-week AdaptiveStim Programming | Manual Adjustments Presented as Button Presses | 35.7 Button presses per day | Standard Deviation 71.8 |
p-value: <0.001Wilcoxon signed rank test
Secondary
NPRS Scores From Baseline to Follow-up Visits at 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.
Time frame: Baseline, 10 weeks and 16 weeks post-implant
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 6-week AdaptiveStim Followed by 6-week Manual Programming | NPRS Scores From Baseline to Follow-up Visits at 10 Weeks and 16 Weeks Post-implant | 5.99 units on a scale | Standard Deviation 1.82 |
| 6-week Manual Followed by 6-week AdaptiveStim Programming | NPRS Scores From Baseline to Follow-up Visits at 10 Weeks and 16 Weeks Post-implant | 4.22 units on a scale | Standard Deviation 2.05 |
| NPRS at Baseline (Subject With Score at 16 Weeks Post-implant) | NPRS Scores From Baseline to Follow-up Visits at 10 Weeks and 16 Weeks Post-implant | 5.90 units on a scale | Standard Deviation 1.81 |
| NPRS at 16 Weeks Post-implant | NPRS Scores From Baseline to Follow-up Visits at 10 Weeks and 16 Weeks Post-implant | 4.41 units on a scale | Standard Deviation 2.18 |
p-value: <0.001Wilcoxon signed rank test
p-value: <0.001Wilcoxon signed rank test
Secondary
Percentage of Subjects With Worsened Pain Relief When Using AdaptiveStim Compared to Manual Programming
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
Population: A total of 71 subjects with completed data were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 6-week AdaptiveStim Followed by 6-week Manual Programming | Percentage of Subjects With Worsened Pain Relief When Using AdaptiveStim Compared to Manual Programming | 0 percentage of participants |
| 6-week Manual Followed by 6-week AdaptiveStim Programming | Percentage of Subjects With Worsened Pain Relief When Using AdaptiveStim Compared to Manual Programming | 5.3 percentage of participants |
95% CI: [0.003, 0.098]