Failed Back Surgery Syndrome, Laminectomy, Post-laminectomy Syndrome, Spinal Cord Syndrome
Conditions
Keywords
Spinal cord stimulation, Back surgery, Chronic pain
Brief summary
Traditionally, pain relief through spinal cord stimulation has been associated with the appearance of paresthesia in the affected area. Several parameters are set to maximize the overexposure zone, such as frequency,and pulse width. Although this technique has improved pain in many patients, paresthesia itself can be uncomfortable. Traditionally, the occurrence of paresthesias has been considered to be a predictor of success in pain elimination, while the non-occurrence of paresthesias would indicate failure. So far, few studies have reported pain relief below the threshold of onset of paresthesia. Some clinical trials for pathologies other than the one considered in this study have achieved relief below the threshold by reducing the amplitude of the stimulus. Recently, however, it has been observed in a pilot study that, by increasing the frequency of spinal cord stimulation to 1 kilohertz, it is possible to significantly improve pain relief compared to less frequent conventional stimulation based on the occurrence of paresthesias. A recent review by the Cochrane Library concluded that conventional spinal cord stimulation for pain relief of Failed Back Surgery Syndrome (or FBSS) requires further clinical studies and better designs to demonstrate its superiority over other therapeutic options. Therefore, although spinal cord stimulation is accepted by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), new techniques are being introduced that offer better results in terms of pain relief. Among these techniques, there is the high frequency mode, which allows avoiding the annoying sensation of paresthesia that substitutes pain with the conventional technique. In order to provide greater rigour and scientific quality, the present study is proposed, in which the conventional spinal cord stimulation (CME) technique (control branch or CME) is compared with paresthesias and a standard frequency (60 hertz) with a high frequency (1000 hertz) EVOLVE system (Evolve workflow - standardized guidance to simplify the trial and implant experience and optimize patient outcomes) (experimental branch or EME) by means of a design with a high degree of scientific evidence, randomising the global sample of patients to each of the two branches of stimulation in the study (blind to the patient) and crossing the branches after a period of washing
Interventions
DEVICEspinal cord stimulation conventional
If the patient has been assigned to the branch of the CME control group, after mapping the search for the pain zone, the neurostimulator is programmed to conventional stimulation.
DEVICEspinal cord stimulation experimental
If the patient has been randomized to the branch of the EME experimental group, after a mapping of the search for the pain zone, a 90% subthreshold stimulation is programmed.
Sponsors
Instituto de Investigación Biomédica de Salamanca
Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
SINGLE (Subject)
Intervention model description
Single-blind, multicenter, crossover
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients over 18 years of age. * Patients with FBSS syndrome with leg pain or leg and back pain. * Get a score on the visual analogue scale (VAS) ≥ 7. * Have received medical pharmacological treatment for at least 6 months after back surgery. * The patient has signed the informed consent form.
Exclusion criteria
* Patients under 18 years of age. * Patients who require a diathermic energy source (microwave, ultrasound or short wave). * Patients with a pacemaker. * Patients carrying a defibrillator. * Patient with a cochlear implant. * Patients with other active implanted devices. * Patients who are scheduled to have any of the following procedures during the study period: an MRI, defibrillation or cardioversion, electrocautery, lithotripsy, radiofrequency or microwave ablation, and any other high-frequency ultrasound procedure, * Women of childbearing age who do not use adequate contraception. * Pregnant or breastfeeding. * Participation in another trial. * Patients who have expressed a desire not to participate in the study and have not formed informed consent. * Patients with a failed spinal cord stimulation implant previously
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparing Visual Analogue Scale (VAS) | Baseline, After first stimulation (5days), after washout and second stimulation (12 days), After 30-day follow-up (42 days) | Visual analogue scale (VAS) at the end of each test phase (either with conventional spinal cord stimulation or with EVOLVE). VAS consists of a 10 centimeter (cm) line, whose ends are defined as the extreme limits of pain (left end corresponds with the absence of pain and the right end with the maximum amount of pain). The patient is asked to point out in the line the place that better correspond to his/her pain, ranging from 0 to 10. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change (%) in VAS Scale at the End of Treatment. | After first stimulation (Five days after baseline), After second stimulation (12 days after baseline), at the end of follow-up (42 days after baseline) | Change (%) in Visual Analogue Scale (VAS) at the end of treatment. * Δ = \[(VAS Initial Visit - VAS Final Visit) / VAS initial visit\] \*100 Please note that positive values indicate a decrease in the VAS scale, which would indicate pain relief, as it was calculated as the value at the earlier time point minus the value at the later time point. |
| Evaluation Disability | Baseline, After first stimulation (+5 days), After washout and second stimulation (+12 days), at the end of follow-up (+42days) | Oswestry Disability Index of the patients: it is a questionnaire consisting of 10 questions with 6 possible answers each. Every answer gives a punctuation from 0 (less disability) to 5 (more disability). This scale is expressed in percentage in which 0 percentage (%) would the least disability and 100 percentage (%) would represent the maximum disability. |
| Number of Participants With Adverse Events in Each Arm | 42 days from baseline | Considering as an adverse event those that result in death, or in severe harm to patient's health (lesion that threatens life, permanent harm on an organ or corporal function, or process that needs a medical or surgical intervention to avoid permanent harm) |
Countries
Spain
Participant flow
Recruitment details
Planned enrollment: 24. Final enrollment: 27. Screened: 28.
Pre-assignment details
27 of 28 patients screened were randomized, as one patient did not meet inclusion/exclusion criteria. All patients underwent both treatments, as the study design was cross-section.
Participants by arm
| Arm | Count |
|---|---|
| CME - EME Branch After mapping the search for the pain area, the neurostimulator is programmed to conventional stimulation (CME) with paresthesia at 60 Hz and a pulse width between 300-450 μs, for 5 days.
The device is then deprogrammed and a 2-day washout period is initiated.
On day 7, EME experimental protocol is initiated: stimulation is programmed at 90% of the subthreshold with a pulse width of 90 μs and frequency of 1000 Hz, placing the bipole in the T9-T10 space, for 5 days. | 13 |
| EME - CME Branch After mapping the search for the pain area, the neurostimulator is programmed to EME experimental protocol is initiated: stimulation is programmed at 90% of the subthreshold with a pulse width of 90 μs and frequency of 1000 Hz, placing the bipole in the T9-T10 space, for 5 days.
The device is then deprogrammed and a 2-day washout period is initiated.
On day 7, conventional stimulation (CME) stimulation is programmed with paresthesia at 60 Hz and a pulse width between 300-450 μs, for 5 days. | 14 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Follow-up (30days) | Lack of Efficacy | 2 | 2 |
Baseline characteristics
| Characteristic | CME - EME Branch | EME - CME Branch | Total |
|---|---|---|---|
| Age, Continuous | 50.8 years STANDARD_DEVIATION 13.1 | 53.9 years STANDARD_DEVIATION 12.6 | 52.4 years STANDARD_DEVIATION 12.7 |
| Body Mass Index (BMI) | 26.0 kg/m2 STANDARD_DEVIATION 4.3 | 28.2 kg/m2 STANDARD_DEVIATION 4.3 | 27.2 kg/m2 STANDARD_DEVIATION 4.4 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Spain | 13 participants | 14 participants | 27 participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Male | 7 Participants | 10 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 27 |
| other Total, other adverse events | 3 / 27 | 4 / 27 |
| serious Total, serious adverse events | 0 / 27 | 0 / 27 |
Outcome results
Primary
Comparing Visual Analogue Scale (VAS)
Visual analogue scale (VAS) at the end of each test phase (either with conventional spinal cord stimulation or with EVOLVE). VAS consists of a 10 centimeter (cm) line, whose ends are defined as the extreme limits of pain (left end corresponds with the absence of pain and the right end with the maximum amount of pain). The patient is asked to point out in the line the place that better correspond to his/her pain, ranging from 0 to 10.
Time frame: Baseline, After first stimulation (5days), after washout and second stimulation (12 days), After 30-day follow-up (42 days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CME -EME Branch | Comparing Visual Analogue Scale (VAS) | Baseline | 9.3 score on a scale | Standard Deviation 1.1 |
| CME -EME Branch | Comparing Visual Analogue Scale (VAS) | After first stimulation (day +5) | 5.7 score on a scale | Standard Deviation 1.7 |
| CME -EME Branch | Comparing Visual Analogue Scale (VAS) | After washout and second stimulation (day +12) | 5.5 score on a scale | Standard Deviation 2.2 |
| CME -EME Branch | Comparing Visual Analogue Scale (VAS) | After Follow-up (day +42) | 4.6 score on a scale | Standard Deviation 1.8 |
| EME-CME Branch | Comparing Visual Analogue Scale (VAS) | After Follow-up (day +42) | 4.2 score on a scale | Standard Deviation 2.2 |
| EME-CME Branch | Comparing Visual Analogue Scale (VAS) | Baseline | 8.6 score on a scale | Standard Deviation 1 |
| EME-CME Branch | Comparing Visual Analogue Scale (VAS) | After washout and second stimulation (day +12) | 5.2 score on a scale | Standard Deviation 2.4 |
| EME-CME Branch | Comparing Visual Analogue Scale (VAS) | After first stimulation (day +5) | 4.9 score on a scale | Standard Deviation 2.3 |
Comparison: Baseline VASp-value: 0.112t-test, 2 sided
Comparison: After first stimulation VASp-value: 0.323t-test, 2 sided
Comparison: After second stimulationp-value: 0.76t-test, 2 sided
Comparison: End of Follow-upp-value: 0.624t-test, 2 sided
Secondary
Change (%) in VAS Scale at the End of Treatment.
Change (%) in Visual Analogue Scale (VAS) at the end of treatment. * Δ = \[(VAS Initial Visit - VAS Final Visit) / VAS initial visit\] \*100 Please note that positive values indicate a decrease in the VAS scale, which would indicate pain relief, as it was calculated as the value at the earlier time point minus the value at the later time point.
Time frame: After first stimulation (Five days after baseline), After second stimulation (12 days after baseline), at the end of follow-up (42 days after baseline)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CME -EME Branch | Change (%) in VAS Scale at the End of Treatment. | After first stimulation | 42.4 percentage of VAS change | Standard Deviation 26 |
| CME -EME Branch | Change (%) in VAS Scale at the End of Treatment. | After second stimulation | 37.8 percentage of VAS change | Standard Deviation 29.1 |
| CME -EME Branch | Change (%) in VAS Scale at the End of Treatment. | End of follow-up | 50.1 percentage of VAS change | Standard Deviation 28.1 |
| EME-CME Branch | Change (%) in VAS Scale at the End of Treatment. | After first stimulation | 37.4 percentage of VAS change | Standard Deviation 20.6 |
| EME-CME Branch | Change (%) in VAS Scale at the End of Treatment. | After second stimulation | 41.5 percentage of VAS change | Standard Deviation 20.3 |
| EME-CME Branch | Change (%) in VAS Scale at the End of Treatment. | End of follow-up | 48.8 percentage of VAS change | Standard Deviation 21.5 |
Comparison: End of Follow-upp-value: 0.908t-test, 2 sided
Comparison: After first stimulationp-value: 0.589t-test, 2 sided
Comparison: After second stimulationp-value: 0.704t-test, 2 sided
Secondary
Evaluation Disability
Oswestry Disability Index of the patients: it is a questionnaire consisting of 10 questions with 6 possible answers each. Every answer gives a punctuation from 0 (less disability) to 5 (more disability). This scale is expressed in percentage in which 0 percentage (%) would the least disability and 100 percentage (%) would represent the maximum disability.
Time frame: Baseline, After first stimulation (+5 days), After washout and second stimulation (+12 days), at the end of follow-up (+42days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CME -EME Branch | Evaluation Disability | Baseline | 59.8 score on a scale | Standard Deviation 14.1 |
| CME -EME Branch | Evaluation Disability | After first stimulation | 44.7 score on a scale | Standard Deviation 15.8 |
| CME -EME Branch | Evaluation Disability | After second stimulation | 43.7 score on a scale | Standard Deviation 18.7 |
| CME -EME Branch | Evaluation Disability | End of Follow-up | 21.8 score on a scale | Standard Deviation 21.6 |
| EME-CME Branch | Evaluation Disability | End of Follow-up | 24.9 score on a scale | Standard Deviation 15.4 |
| EME-CME Branch | Evaluation Disability | Baseline | 65.7 score on a scale | Standard Deviation 10.5 |
| EME-CME Branch | Evaluation Disability | After second stimulation | 43.7 score on a scale | Standard Deviation 21.8 |
| EME-CME Branch | Evaluation Disability | After first stimulation | 41.5 score on a scale | Standard Deviation 21.4 |
Comparison: Baselinep-value: 0.231t-test, 2 sided
Comparison: After first stimulationp-value: 0.663t-test, 2 sided
Comparison: After second stimulationp-value: 0.998t-test, 2 sided
Comparison: End of Follow-upp-value: 0.713t-test, 2 sided
Secondary
Number of Participants With Adverse Events in Each Arm
Considering as an adverse event those that result in death, or in severe harm to patient's health (lesion that threatens life, permanent harm on an organ or corporal function, or process that needs a medical or surgical intervention to avoid permanent harm)
Time frame: 42 days from baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CME -EME Branch | Number of Participants With Adverse Events in Each Arm | 0 Participants |
| EME-CME Branch | Number of Participants With Adverse Events in Each Arm | 0 Participants |