Spinal Cord Stimulation in Patients With Post-Laminectomy Syndrome in Testing Phase

• Sponsor: Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León (Other)
• Overall Status: Completed
• CT.gov ID: NCT03702010
• Collaborator: Instituto de Investigación Biomédica de Salamanca (Other)
• Enrollment: 27
• Locations: 2
• Arms: 2
• Actual Duration (Months): 19.4
• Patients Per Site: 13.5
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Laminectomy; Post-laminectomy Syndrome; Spinal Cord Syndrome; Failed Back Surgery Syndrome	Device: spinal cord stimulation conventional; Device: spinal cord stimulation experimental	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Single-blind, multicenter, crossoverSingle-blind, multicenter, crossover
• Masking: Single (Participant)
• Primary Purpose: Health Services Research
• Official Title: Randomized, Single-blind, Multicenter, Crossover, Controlled Clinical Trial to Compare Difference on the Visual Analogue Scale With Two Modes of Spinal Cord Stimulation in Patients With Post-Laminectomy Syndrome in Testing Phase
• Actual Study Start Date: Nov 20, 2018
• Actual Primary Completion Date: Jul 1, 2020
• Actual Study Completion Date: Jul 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: CME branch In this study, the conventional spinal cord stimulation method (control Branch-CME branch)	Device: spinal 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.; Other Names: CME
Experimental: EME branch In this study, the experimental spinal cord stimulation method are used in the same patient with the EVOLVE programming guide (EME branch)	Device: spinal 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.; Other Names: EME

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital San Pedro de Logroño	Logroño	La Rioja	Spain	26006
2	Complejo Asistencial Universitario de Salamanca	Salamanca		Spain	37007

Sponsors and Collaborators

• Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León
• Instituto de Investigación Biomédica de Salamanca

Investigators

• Study Director: Francisco J Sánchez-Montero, MD, IBSAL-Instituto de Investigación Biomédica de Salamanca

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 4, 2018
• Informed Consent Form - May 8, 2018

More Information

Publications

None provided.

• Responsible Party: Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León
• ClinicalTrials.gov Identifier: NCT03702010
• Other Study ID Numbers: EST-MED-2018-01; E.C.P.S. 18/1398
• First Posted: Oct 10, 2018
• Last Update Posted: Sep 1, 2021
• Last Verified: Aug 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León: Spinal cord stimulation; Back surgery; Chronic pain
• Additional relevant MeSH terms: Spinal Diseases; Spinal Cord Injuries; Syndrome; Failed Back Surgery Syndrome; Postoperative Complications

Study Results

Participant Flow

Recruitment Details	Planned enrollment: 24. Final enrollment: 27. Screened: 28.
Pre-assignment Detail	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.

Arm/Group Title	CME - EME Branch	EME - CME Branch
Arm/Group Description	In this study, the conventional spinal cord stimulation method (control Branch-CME branch) CME control group: after mapping the search for the pain area, the neurostimulator is programmed to conventional stimulation 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 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.	In this study, the experimental spinal cord stimulation method are used in the same patient with the EVOLVE programming guide (EME branch) EME experimental group: fter mapping the search for the pain area, the neurostimulator 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 CME stimulation is programmed with paresthesia at 60 Hz and a pulse width between 300-450 μs, for 5 days.
Period Title: First Stimulation (5 Days)
STARTED	13	14
COMPLETED	13	14
NOT COMPLETED	0	0
Period Title: First Stimulation (5 Days)
STARTED	13	14
COMPLETED	13	14
NOT COMPLETED	0	0
Period Title: First Stimulation (5 Days)
STARTED	13	14
COMPLETED	11	12
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	CME - EME Branch	EME - CME Branch	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	13	14	27
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.8 (13.1)	53.9 (12.6)	52.4 (12.7)
Sex: Female, Male (Count of Participants)
Female	6 46.2%	4 28.6%	10 37%
Male	7 53.8%	10 71.4%	17 63%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Spain	13 100%	14 100%	27 100%
Body Mass Index (BMI) (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	26.0 (4.3)	28.2 (4.3)	27.2 (4.4)

Outcome Measures

1. Primary Outcome

Title	Comparing Visual Analogue Scale (VAS)
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CME -EME Branch	EME-CME Branch
Arm/Group Description	Conventional CME: after mapping the search for the pain area, the neurostimulator is programmed to conventional stimulation 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 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.	EVOLVE programming guide (EME): after mapping the search for the pain area, the neurostimulator 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, CME protocol is initiated: stimulation is programmed to conventional stimulation with paresthesia at 60 Hz and a pulse width between 300-450 μs, for 5 days.
Measure Participants	13	14
Baseline	9.3 (1.1)	8.6 (1.0)
After first stimulation (day +5)	5.7 (1.7)	4.9 (2.3)
After washout and second stimulation (day +12)	5.5 (2.2)	5.2 (2.4)
After Follow-up (day +42)	4.6 (1.8)	4.2 (2.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CME -EME Branch, EME-CME Branch
	Comments	Baseline VAS
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.112
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CME -EME Branch, EME-CME Branch
	Comments	After first stimulation VAS
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.323
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CME -EME Branch, EME-CME Branch
	Comments	After second stimulation
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.760
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CME -EME Branch, EME-CME Branch
	Comments	End of Follow-up
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.624
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Change (%) in VAS Scale at the End of Treatment.
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CME - EME Branch	EME - CME Branch
Arm/Group Description	Conventional spinal cord stimulation (CME) method for 5 days. Washout of 2 days. Experimental spinal cord stimulation (EME) for 5 days.	Experimental spinal cord stimulation (EME) method for 5 days. Washout of 2 days. Conventional spinal cord stimulation (CME) for 5 days.
Measure Participants	13	14
After first stimulation	42.4 (26.0)	37.4 (20.6)
After second stimulation	37.8 (29.1)	41.5 (20.3)
End of follow-up	50.1 (28.1)	48.8 (21.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CME -EME Branch, EME-CME Branch
	Comments	After first stimulation
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.589
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CME -EME Branch, EME-CME Branch
	Comments	After second stimulation
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.704
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CME -EME Branch, EME-CME Branch
	Comments	End of Follow-up
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.908
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Evaluation Disability
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CME - EME Branch	EME - CME Branch
Arm/Group Description	CME conventional stimulation for 5 days, Washout for 2 days. EME evolve experimental stimulation for 5 days.	EVOLVE programming guide (EME) experimental stimulation for 5 days. Washout for 2 days. Conventional stimulation (CME) for 5 days.
Measure Participants	13	14
Baseline	59.8 (14.1)	65.7 (10.5)
After first stimulation	44.7 (15.8)	41.5 (21.4)
After second stimulation	43.7 (18.7)	43.7 (21.8)
End of Follow-up	21.8 (21.6)	24.9 (15.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CME -EME Branch, EME-CME Branch
	Comments	Baseline
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.231
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CME -EME Branch, EME-CME Branch
	Comments	After first stimulation
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.663
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CME -EME Branch, EME-CME Branch
	Comments	After second stimulation
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.998
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CME -EME Branch, EME-CME Branch
	Comments	End of Follow-up
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.713
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Number of Participants With Adverse Events in Each Arm
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CME - EME	EME - CME
Arm/Group Description	Conventional stimulation for 5 days Washout for days Experimental stimulation for 5 days	EVOLVE stimulation for 5 days Washout for 2 days Conventional stimulation for 5 days.
Measure Participants	13	14
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	From baseline to the end of Follow-up (42 days).
Arm/Group Title	CME - Conventional Stimulation		EME - EVOLVE Experimental Stimulation
Arm/Group Description	Conventional stimulation with paresthesia at 60 Hz and a pulse width between 300-450 μs, for 5 days.		The neurostimulator is programmed to 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.
All Cause Mortality
	CME - Conventional Stimulation		EME - EVOLVE Experimental Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/27 (0%)
Serious Adverse Events
	CME - Conventional Stimulation		EME - EVOLVE Experimental Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/27 (0%)
Other (Not Including Serious) Adverse Events
	CME - Conventional Stimulation		EME - EVOLVE Experimental Stimulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/27 (11.1%)		4/27 (14.8%)
Injury, poisoning and procedural complications
post-dural puncture headache	1/27 (3.7%)	1	1/27 (3.7%)	1
Skin and subcutaneous tissue disorders
Dermatitis	1/27 (3.7%)	1	0/27 (0%)	0
Surgical and medical procedures
Pain	0/27 (0%)	0	1/27 (3.7%)	1
Electrode migration	1/27 (3.7%)	1	2/27 (7.4%)	2
Abnormal stimulation	0/27 (0%)	0	1/27 (3.7%)	1

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.