Failed Back Surgery SyndromeCDSSNCT04735159
Clinical Decision Support System (CDSS) in Neurostimulation Therapy
A study testing SCS implanted with Precision SpectraTM in people with Failed Back Surgery Syndrome, run by General University Hospital of Valencia.
Trial summary
Chronic pain is correlated with alterations in the structure and function of the brain, developed according to the phenotype of pain. Still today, the data on functional connectivity (FC), on chronic back pain, in patients with failed back surgery syndrome (FBSS), is limited. Read more about this study
- Who is it for?
- Ages 20 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Failed Back Surgery Syndrome
- What is being tested?
- SCS implanted with Precision SpectraTM
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- 20 Nov 2016to 30 Jun 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients presenting pain of more than 6 months in duration
- VAS Score at baseline ≥ 5
- Patients with degenerative spine pain. Non specific low-back pain, nociceptive pain / mixed neuropathic
- Post-operative spine pain, failed back surgery syndrome, mixed pain
- Low consumption of analgesic and adjuvant drugs.
- Pure radiculopathy
- No suffering other serious chronic diseases.
- No history of drug or alcohol.
Who cannot join
- Having implanted pacemakers, stimulators or hearing aids incompatible with MR imaging.
- Patients presenting psychiatric illness or significant cognitive deficits.
- Psychological instability.
- History of alcohol and drugs.
- Severe coagulopathy.
- Pending Surgery.
About this study
Official title: Development of a Predictive Model of Effectiveness for the Implantation of Electrical Neurostimulators in Patients With Chronic Pain Using Imaging Biomarkers Extracted From Magnetic Resonance
Chronic pain is correlated with alterations in the structure and function of the brain, developed according to the phenotype of pain. Still today, the data on functional connectivity (FC), on chronic back pain, in patients with failed back surgery syndrome (FBSS), is limited. The selection process for the ideal candidate for spinal cord stimulation (SCS) is based on results from test and functional variables analysis as well as pain evaluation. In addition to the difficulties in the initial selection of patients and the predictive analysis of the test phase, which undoubtedly impact on the results in the middle and long term, the rate of explants is one of the most important concerns, in the analysis of suitability of implanted candidates. The hypothesis is that the structural and functional quantitative information provided by imaging biomarkers will improve the characterization of the patients compared to the characterization with the current clinical variables alone and this will allow establishing a CDSS that improve the effectiveness of the SCS implantation, optimizing human, economic and psychological resources.
A prospective, consecutive and observational, open-label, single-center study conducted at the Multidisciplinary Pain Management Department of our University Hospital. A total of 69 subjects were initially included in the study. The population split in 3 groups:
Read more
- Interventional Group-SCS, included 35 patients with failed back surgery syndrome (FBSS) who were treated with SCS implants.
- Comparator group included 23 patients with patients with chronic low-back pain who were treated with conventional medication (CM) for their pain.
- Control Group included 11 subjects as health controls who volunteered to participate in the study.
MR images were obtained in a 1.5T MR system (Ingenia, Philips, Best, The Netherlands) using an 8-channel head coil.Clinical variables were evaluated at two different time points baseline and 12 months after SCS implantation or conventional medication. An ad hoc database was created to evaluate the different variables involved in pain , including sociodemographic variables (age, gender, level of studies and marital status), clinical variables (anxiety, depression, sleeping hours, resilience, NRS, the Pain Detect Questionnaire (PD-Q)) , and the images obtained from the fMRI.
Read the detailed description
Primary objective:To develop a predictive model integrated in a clinical decision support system (CDSS) feed by neuroimaging quantitative information objectively extracted from Magnetic Resonance (MR) images, which maximizes the appropriate use and effectiveness of electrical stimulation devices surgically implanted in selected patients with chronic pain.
Exploratory Objectives:
- -Analyze functional and anatomical brain connectivity patterns in patients with chronic pain , to develop a predictive model based on quantitative magnetic resonance neuroimaging which maximizes the effectiveness of neurostimulation devices surgically implanted in patients with chronic pain.
- -Analyze the relationship between neuroimaging biomarkers and the different clinical scales and variables captured from each patient (VAS, Oswestry Disability Index, DN4, Pain Detect, Moss, SF12, coping scale, optimism, resilience and HAD).
Test Device:1.5 Tesla MR system (Philips Healthcare, Best, The Netherlands) Boston Scientific Neuromodulation (BSN) Precision Spectra™ Spinal Cord Stimulation System with Illumina 3D™ Software and 32 contacts.
Device Description: Precision Spectra™ system IPG is a multiple independent current controlled pulse generator, capable of delivering current through 32 contacts. It is powered by a 3D programming software that considers the anatomical position of the leads. Two models of SCS leads will be provided, featuring 8 or 16 contacts with 1.3 mm diameter, 3 mm contact length, and contact spacing of 1, 4 or 6 mm. The use of SCS extensions will be optional to connect the IPG.
fMR description: The MR experiment will be consistent with on-label requirements. The MR procedure will be performed prior to the device implantation to avoid bias. Even more, the Food and Drug Administration (FDA) does not recommend the examination of patients with this kind of devices for security reasons.
Examinations will be performed in a 1'5 Tesla MR system (Philips Healthcare, Best, The Netherlands) at the Quiron Hospital. Decision of magnetic field is based on the quality of the examinations and must rely on label products and approval of company for interaction with implanted system.
A head coil with 8 reception channels will be used. Once the patient has been positioned in the system, initial and fast localization images will be acquired in order to properly plan the MR sequences of the research study.
After planning, a resting-state functional MR (rs-fMR) imaging sequence will be acquired, asking to the patient to be quiet with the eyes closed and thinking in a blue sky. The acquisition parameters will consist of an Echo Planar (EPI) dynamic T2* sequence, full brain coverage with the following parameters: TR=2000 ms; TE=30 ms; voxel size, 1.8 × 1.8 x 3.5 mm; flip angle, 90º; 40 axial slices; acquisition time 5:20 min.
A DTI MR sequence will be acquired in order to analyze white matter microstructure and connectivity by tractography techniques with the following parameters: Spin-Echo Echo Planar Imaging (SE-EPI) sequence, single shot; full brain coverage; 64 gradient directions; b-value, 1300 s/mm2; TR=6200 ms; TE=67 ms; voxel size, 2 x 2 x 2 mm; 60 axial slices; acquisition time 9:40 min.
An additional anatomic sequence will allow overlying structural and functional results and, in addition, obtaining the volumetry values of each brain region. The sequence parameters are: T1-weighted 3D gradient echo sequence (GRE), full brain coverage; TR=11.6 ms; TE=5.69; voxel size, 0.48 x 0.48 x 0.50 mm; flip angle, 8º; 280 axial slices; acquisition time 5:36 min.
After image acquisition, all data sets will be sent to the Imaging Biomarkers Platform of the Biomedical Imaging Research Group (GIBI230) of the La Fe Research Institute.
The fMR images will be aligned in order to correct possible small patient's head movements during examination. For that, the open source SPM8 (Statistical Parametric Mapping, http://www.fil.ion.ucl.ac.uk/spm/) software tool will be used. After movement correction, a temporal correction will be applied optimizing the slice timing. Images will be then normalized to a standardized brain template in order to allow for the study of the oscillations between individuals. After such processes, data will be filtered by a3D-Gaussian kernel in order to increase signal-to-noise ratio (SNR) while minimizing inter-subject differences. Finally, the application of independent component analysis (ICA) algorithms will allow for the extraction of brain activation maps in the subject during the acquisition.
The analysis of the DTI MR data for extracting white matter tracts connectivity will be performed with the open-source FSL software tool (http://www.fmrib.ox.ac.uk/fsl/). An initial Eddy currents correction will be applied to the images, in order to minimize slight images displacements and geometry distortions. The brain will be then segmented using the BET algorithm and brain data of all patients will be normalized to a common template for the group-based analysis. After this process, fractional anisotropy (FA), diffusivity (D) and orientation maps will be obtained .
Once the MR images have been processed, the structural and functional connectivity properties have to be extracted from the regions of interest (ROI). The positioning of these regions will be obtained from the zones involved in the Default Mode Network (DMN). The DMN might take an important role in pain perception and shows a high correlation with the symptoms described by patients, which makes this network useful for the prediction of patient response after the implantation of electrical stimulation, either at a functional or at a structural level.
Since images will be normalized to a common template, the automated area labeling AAL-tool will be used to define the regions of interest of the study, that compound the DMN and are formed by the medial temporal lobe, prefrontal cortex, posterior cingulate, precuneus and the parietal cortex. After measurement the connectivity parameters in these regions, a predictive model will be developed by combining clinical variables (scales and symptoms of each patient) and neuroimaging information. These models will be initially adjusted with a total of 30 patients (training data) and later validated in a group of 30 patients (validation data), obtaining thereafter results of specificity, sensitivity and models precision.
- Conditions
- Failed Back Surgery Syndrome
- Being tested
- SCS implanted with Precision SpectraTM
- Medical subject headings
- Failed Back Surgery Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SCS implanted with Precision SpectraTMDevice
Also called Functional Magnetic Resonance performed after implating SCS
Analyze the relationship between neuroimaging biomarkers and the different clinical scales and variables captured from each patient
| Study group | Role | What they receive |
|---|---|---|
| Study group-SCS Impanted | Active comparator | 30 patients with chronic pain (at least 6 months) with pre- and post-surgery evaluation (imaging and clinical evaluation) implanted with Precision SpectraTM for the validation study and for the construction of the predictive model. Receives: Device: SCS implanted with Precision SpectraTM |
| Comparator-chronic pain | No intervention | 20 patients with chronic pain (at least 6 months) with degenerative spine pain. Non-specific low-back pain, nociceptive pain / mixed neuropathic. This will be the comparator group |
| Control-healthy volunteers | No intervention | 10 volunteers without pain or related disease, age less than 25 years, to establish a control group whose pattern is used as a comparator with chronic pain groups. This is the control group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical decision support system (CDSS) for selection of patients candidates for SCS implant
to analyze the neuronal circuits involved in FBSS patients in order to extract predictive imaging biomarkers capable of determining the characteristics of patients that predict the success of SCS implants. This information might be used to develop a CDSS to maximize the effectiveness of electrical stimulation devices surgically implanted in patients with chronic pain.
Measured: 12 months
Secondary outcomes (1)
neuronal circuits involved in chronic pain
to describe neuronal circuits involved in chronic pain by comparation between patients and control subjects; identify differences in the neural circuits between patients who have successfully undergone the implantation of the SCS and who failed the trial phase attending to the current criteria
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2021
- Study start20 Nov 2016
- Primary completion30 Jun 2018
- Study completion30 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (29)Papers the sponsor has linked to this study.
- Other trials for Failed Back Surgery SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- General University Hospital of Valencia
- Sponsor type
- University, hospital or other
- Collaborators
- Boston Scientific Corporation
- Responsible party
- Principal investigator, Jose De Andres, General University Hospital of Valencia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04735159
- Sponsor's protocol ID
- Biomarcadores-RM
- Acronym
- CDSS
- Status last verified
- Feb 2021
- First submitted
- 26 Jan 2021
- Last updated
- 4 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Simpson EL, Duenas A, Holmes MW, Papaioannou D, Chilcott J. Spinal cord stimulation for chronic pain of neuropathic or ischaemic origin: systematic review and economic evaluation. Health Technol Assess. 2009 Mar;13(17):iii, ix-x, 1-154. doi: 10.3310/hta13170.
PubMed 19331797Turner JA, Loeser JD, Deyo RA, Sanders SB. Spinal cord stimulation for patients with failed back surgery syndrome or complex regional pain syndrome: a systematic review of effectiveness and complications. Pain. 2004 Mar;108(1-2):137-47. doi: 10.1016/j.pain.2003.12.016.
PubMed 15109517Borsook D, Sava S, Becerra L. The pain imaging revolution: advancing pain into the 21st century. Neuroscientist. 2010 Apr;16(2):171-85. doi: 10.1177/1073858409349902.
PubMed 20400714Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL. A default mode of brain function. Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):676-82. doi: 10.1073/pnas.98.2.676.
PubMed 11209064Taylor KS, Seminowicz DA, Davis KD. Two systems of resting state connectivity between the insula and cingulate cortex. Hum Brain Mapp. 2009 Sep;30(9):2731-45. doi: 10.1002/hbm.20705.
PubMed 19072897Hodaie M, Chen DQ, Quan J, Laperriere N. Tractography delineates microstructural changes in the trigeminal nerve after focal radiosurgery for trigeminal neuralgia. PLoS One. 2012;7(3):e32745. doi: 10.1371/journal.pone.0032745. Epub 2012 Mar 6.
PubMed 22412918Leal PRL, Roch JA, Hermier M, Souza MAN, Cristino-Filho G, Sindou M. Structural abnormalities of the trigeminal root revealed by diffusion tensor imaging in patients with trigeminal neuralgia caused by neurovascular compression: a prospective, double-blind, controlled study. Pain. 2011 Oct;152(10):2357-2364. doi: 10.1016/j.pain.2011.06.029. Epub 2011 Aug 10.
PubMed 21835547Lutz J, Jager L, de Quervain D, Krauseneck T, Padberg F, Wichnalek M, Beyer A, Stahl R, Zirngibl B, Morhard D, Reiser M, Schelling G. White and gray matter abnormalities in the brain of patients with fibromyalgia: a diffusion-tensor and volumetric imaging study. Arthritis Rheum. 2008 Dec;58(12):3960-9. doi: 10.1002/art.24070.
PubMed 19035484Ruscheweyh R, Deppe M, Lohmann H, Stehling C, Floel A, Ringelstein BE, Knecht S. Pain is associated with regional grey matter reduction in the general population. Pain. 2011 Apr;152(4):904-911. doi: 10.1016/j.pain.2011.01.013. Epub 2011 Feb 5.
PubMed 21296501Gustin SM, Peck CC, Wilcox SL, Nash PG, Murray GM, Henderson LA. Different pain, different brain: thalamic anatomy in neuropathic and non-neuropathic chronic pain syndromes. J Neurosci. 2011 Apr 20;31(16):5956-64. doi: 10.1523/JNEUROSCI.5980-10.2011.
PubMed 21508220Deer TR, Grider JS, Lamer TJ, Pope JE, Falowski S, Hunter CW, Provenzano DA, Slavin KV, Russo M, Carayannopoulos A, Shah JM, Harned ME, Hagedorn JM, Bolash RB, Arle JE, Kapural L, Amirdelfan K, Jain S, Liem L, Carlson JD, Malinowski MN, Bendel M, Yang A, Aiyer R, Valimahomed A, Antony A, Craig J, Fishman MA, Al-Kaisy AA, Christelis N, Rosenquist RW, Levy RM, Mekhail N. A Systematic Literature Review of Spine Neurostimulation Therapies for the Treatment of Pain. Pain Med. 2020 Nov 7;21(7):1421-1432. doi: 10.1093/pm/pnz353.
PubMed 32034422De Andres J, Navarrete-Rueda F, Fabregat G, Garcia-Gutierrez MS, Monsalve-Dolz V, Harutyunyan A, Minguez-Marti A, Rodriguez-Lopez R, Manzanares J. Differences in Gene Expression of Endogenous Opioid Peptide Precursor, Cannabinoid 1 and 2 Receptors and Interleukin Beta in Peripheral Blood Mononuclear Cells of Patients With Refractory Failed Back Surgery Syndrome Treated With Spinal Cord Stimulation: Markers of Therapeutic Outcomes? Neuromodulation. 2021 Jan;24(1):49-60. doi: 10.1111/ner.13111. Epub 2020 Feb 6.
PubMed 32027775Dworkin RH, O'Connor AB, Kent J, Mackey SC, Raja SN, Stacey BR, Levy RM, Backonja M, Baron R, Harke H, Loeser JD, Treede RD, Turk DC, Wells CD. Interventional management of neuropathic pain: NeuPSIG recommendations. Pain. 2013 Nov;154(11):2249-2261. doi: 10.1016/j.pain.2013.06.004. Epub 2013 Jun 6.
PubMed 23748119De Andres J, Monsalve-Dolz V, Fabregat-Cid G, Villanueva-Perez V, Harutyunyan A, Asensio-Samper JM, Sanchis-Lopez N. Prospective, Randomized Blind Effect-on-Outcome Study of Conventional vs High-Frequency Spinal Cord Stimulation in Patients with Pain and Disability Due to Failed Back Surgery Syndrome. Pain Med. 2017 Dec 1;18(12):2401-2421. doi: 10.1093/pm/pnx241.
PubMed 29126228Oakley JC, Krames ES, Stamatos J, Foster AM. Successful long-term outcomes of spinal cord stimulation despite limited pain relief during temporary trialing. Neuromodulation. 2008 Jan;11(1):66-73. doi: 10.1111/j.1525-1403.2007.00145.x.
PubMed 22150994
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development of a Predictive Model of Effectiveness for the Implantation of Electrical Neurostimulators in Patients With Chronic Pain Using Imaging Biomarkers Extracted From Magnetic Resonance
- ClinicalTrials.gov ID
- NCT04735159
- Acronym / sponsor ID
- CDSS / Biomarcadores-RM
- Conditions
- Failed Back Surgery Syndrome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- General University Hospital of ValenciaUniversity, hospital or other
- Collaborators
- Boston Scientific Corporation
- Study start
- 20 Nov 2016 (actual)
- Primary completion
- 30 Jun 2018 (actual)
- Study completion
- 30 Jun 2019 (actual)
- First posted
- 3 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic pain is correlated with alterations in the structure and function of the brain, developed according to the phenotype of pain. Still today, the data on functional connectivity (FC), on chronic back pain, in patients with failed back surgery syndrome (FBSS), is limited. The selection process for the ideal candidate for spinal cord stimulation (SCS) is based on results from test and functional variables analysis as well as pain evaluation. In addition to the difficulties in the initial selection of patients and the predictive analysis of the test phase, which undoubtedly impact on the results in the middle and long term, the rate of explants is one of the most important concerns, in the analysis of suitability of implanted candidates. The hypothesis is that the structural and functional quantitative information provided by imaging biomarkers will improve the characterization of the patients compared to the characterization with the current clinical variables alone and this will allow establishing a CDSS that improve the effectiveness of the SCS implantation, optimizing human, economic and psychological resources.
A prospective, consecutive and observational, open-label, single-center study conducted at the Multidisciplinary Pain Management Department of our University Hospital. A total of 69 subjects were initially included in the study. The population split in 3 groups:
- Interventional Group-SCS, included 35 patients with failed back surgery syndrome (FBSS) who were treated with SCS implants.
- Comparator group included 23 patients with patients with chronic low-back pain who were treated with conventional medication (CM) for their pain.
- Control Group included 11 subjects as health controls who volunteered to participate in the study.
MR images were obtained in a 1.5T MR system (Ingenia, Philips, Best, The Netherlands) using an 8-channel head coil.Clinical variables were evaluated at two different time points baseline and 12 months after SCS implantation or conventional medication. An ad hoc database was created to evaluate the different variables involved in pain , including sociodemographic variables (age, gender, level of studies and marital status), clinical variables (anxiety, depression, sleeping hours, resilience, NRS, the Pain Detect Questionnaire (PD-Q)) , and the images obtained from the fMRI.
Detailed description
Primary objective:To develop a predictive model integrated in a clinical decision support system (CDSS) feed by neuroimaging quantitative information objectively extracted from Magnetic Resonance (MR) images, which maximizes the appropriate use and effectiveness of electrical stimulation devices surgically implanted in selected patients with chronic pain.
Exploratory Objectives:
- -Analyze functional and anatomical brain connectivity patterns in patients with chronic pain , to develop a predictive model based on quantitative magnetic resonance neuroimaging which maximizes the effectiveness of neurostimulation devices surgically implanted in patients with chronic pain.
- -Analyze the relationship between neuroimaging biomarkers and the different clinical scales and variables captured from each patient (VAS, Oswestry Disability Index, DN4, Pain Detect, Moss, SF12, coping scale, optimism, resilience and HAD).
Test Device:1.5 Tesla MR system (Philips Healthcare, Best, The Netherlands) Boston Scientific Neuromodulation (BSN) Precision Spectra™ Spinal Cord Stimulation System with Illumina 3D™ Software and 32 contacts.
Device Description: Precision Spectra™ system IPG is a multiple independent current controlled pulse generator, capable of delivering current through 32 contacts. It is powered by a 3D programming software that considers the anatomical position of the leads. Two models of SCS leads will be provided, featuring 8 or 16 contacts with 1.3 mm diameter, 3 mm contact length, and contact spacing of 1, 4 or 6 mm. The use of SCS extensions will be optional to connect the IPG.
fMR description: The MR experiment will be consistent with on-label requirements. The MR procedure will be performed prior to the device implantation to avoid bias. Even more, the Food and Drug Administration (FDA) does not recommend the examination of patients with this kind of devices for security reasons.
Examinations will be performed in a 1'5 Tesla MR system (Philips Healthcare, Best, The Netherlands) at the Quiron Hospital. Decision of magnetic field is based on the quality of the examinations and must rely on label products and approval of company for interaction with implanted system.
A head coil with 8 reception channels will be used. Once the patient has been positioned in the system, initial and fast localization images will be acquired in order to properly plan the MR sequences of the research study.
After planning, a resting-state functional MR (rs-fMR) imaging sequence will be acquired, asking to the patient to be quiet with the eyes closed and thinking in a blue sky. The acquisition parameters will consist of an Echo Planar (EPI) dynamic T2* sequence, full brain coverage with the following parameters: TR=2000 ms; TE=30 ms; voxel size, 1.8 × 1.8 x 3.5 mm; flip angle, 90º; 40 axial slices; acquisition time 5:20 min.
A DTI MR sequence will be acquired in order to analyze white matter microstructure and connectivity by tractography techniques with the following parameters: Spin-Echo Echo Planar Imaging (SE-EPI) sequence, single shot; full brain coverage; 64 gradient directions; b-value, 1300 s/mm2; TR=6200 ms; TE=67 ms; voxel size, 2 x 2 x 2 mm; 60 axial slices; acquisition time 9:40 min.
An additional anatomic sequence will allow overlying structural and functional results and, in addition, obtaining the volumetry values of each brain region. The sequence parameters are: T1-weighted 3D gradient echo sequence (GRE), full brain coverage; TR=11.6 ms; TE=5.69; voxel size, 0.48 x 0.48 x 0.50 mm; flip angle, 8º; 280 axial slices; acquisition time 5:36 min.
After image acquisition, all data sets will be sent to the Imaging Biomarkers Platform of the Biomedical Imaging Research Group (GIBI230) of the La Fe Research Institute.
The fMR images will be aligned in order to correct possible small patient's head movements during examination. For that, the open source SPM8 (Statistical Parametric Mapping, http://www.fil.ion.ucl.ac.uk/spm/) software tool will be used. After movement correction, a temporal correction will be applied optimizing the slice timing. Images will be then normalized to a standardized brain template in order to allow for the study of the oscillations between individuals. After such processes, data will be filtered by a3D-Gaussian kernel in order to increase signal-to-noise ratio (SNR) while minimizing inter-subject differences. Finally, the application of independent component analysis (ICA) algorithms will allow for the extraction of brain activation maps in the subject during the acquisition.
The analysis of the DTI MR data for extracting white matter tracts connectivity will be performed with the open-source FSL software tool (http://www.fmrib.ox.ac.uk/fsl/). An initial Eddy currents correction will be applied to the images, in order to minimize slight images displacements and geometry distortions. The brain will be then segmented using the BET algorithm and brain data of all patients will be normalized to a common template for the group-based analysis. After this process, fractional anisotropy (FA), diffusivity (D) and orientation maps will be obtained .
Once the MR images have been processed, the structural and functional connectivity properties have to be extracted from the regions of interest (ROI). The positioning of these regions will be obtained from the zones involved in the Default Mode Network (DMN). The DMN might take an important role in pain perception and shows a high correlation with the symptoms described by patients, which makes this network useful for the prediction of patient response after the implantation of electrical stimulation, either at a functional or at a structural level.
Since images will be normalized to a common template, the automated area labeling AAL-tool will be used to define the regions of interest of the study, that compound the DMN and are formed by the medial temporal lobe, prefrontal cortex, posterior cingulate, precuneus and the parietal cortex. After measurement the connectivity parameters in these regions, a predictive model will be developed by combining clinical variables (scales and symptoms of each patient) and neuroimaging information. These models will be initially adjusted with a total of 30 patients (training data) and later validated in a group of 30 patients (validation data), obtaining thereafter results of specificity, sensitivity and models precision.
Study design
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Study group-SCS Impanted | Active comparator | Device: SCS implanted with Precision SpectraTM30 patients with chronic pain (at least 6 months) with pre- and post-surgery evaluation (imaging and clinical evaluation) implanted with Precision SpectraTM for the validation study and for the construction of the predictive model. |
| Comparator-chronic pain | No intervention | –20 patients with chronic pain (at least 6 months) with degenerative spine pain. Non-specific low-back pain, nociceptive pain / mixed neuropathic. This will be the comparator group |
| Control-healthy volunteers | No intervention | –10 volunteers without pain or related disease, age less than 25 years, to establish a control group whose pattern is used as a comparator with chronic pain groups. This is the control group |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients presenting pain of more than 6 months in duration
- VAS Score at baseline ≥ 5
- Patients with degenerative spine pain. Non specific low-back pain, nociceptive pain / mixed neuropathic
- Post-operative spine pain, failed back surgery syndrome, mixed pain
- Low consumption of analgesic and adjuvant drugs.
Key exclusion criteria (6 listed)
- Having implanted pacemakers, stimulators or hearing aids incompatible with MR imaging.
- Patients presenting psychiatric illness or significant cognitive deficits.
- Psychological instability.
- History of alcohol and drugs.
- Severe coagulopathy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SCS implanted with Precision SpectraTMAlso: Functional Magnetic Resonance performed after implating SCSAnalyze the relationship between neuroimaging biomarkers and the different clinical scales and variables captured from each patient | Device | Study group-SCS Impanted |
Primary outcome
Clinical decision support system (CDSS) for selection of patients candidates for SCS implant
Time frame: 12 months
to analyze the neuronal circuits involved in FBSS patients in order to extract predictive imaging biomarkers capable of determining the characteristics of patients that predict the success of SCS implants. This information might be used to develop a CDSS to maximize the effectiveness of electrical stimulation devices surgically implanted in patients with chronic pain.
1 secondary outcome
neuronal circuits involved in chronic pain
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2021.
- Background: PubMed 19331797Simpson EL, Duenas A, Holmes MW, Papaioannou D, Chilcott J. Spinal cord stimulation for chronic pain of neuropathic or ischaemic origin: systematic review and economic evaluation. Health Technol Assess. 2009 Mar;13(17):iii, ix-x, 1-154. doi: 10.3310/hta13170.
- Background: PubMed 15109517Turner JA, Loeser JD, Deyo RA, Sanders SB. Spinal cord stimulation for patients with failed back surgery syndrome or complex regional pain syndrome: a systematic review of effectiveness and complications. Pain. 2004 Mar;108(1-2):137-47. doi: 10.1016/j.pain.2003.12.016.
- Background: PubMed 20400714Borsook D, Sava S, Becerra L. The pain imaging revolution: advancing pain into the 21st century. Neuroscientist. 2010 Apr;16(2):171-85. doi: 10.1177/1073858409349902.
- Background: PubMed 11209064Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL. A default mode of brain function. Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):676-82. doi: 10.1073/pnas.98.2.676.
- Background: PubMed 19072897Taylor KS, Seminowicz DA, Davis KD. Two systems of resting state connectivity between the insula and cingulate cortex. Hum Brain Mapp. 2009 Sep;30(9):2731-45. doi: 10.1002/hbm.20705.
- Background: PubMed 22412918Hodaie M, Chen DQ, Quan J, Laperriere N. Tractography delineates microstructural changes in the trigeminal nerve after focal radiosurgery for trigeminal neuralgia. PLoS One. 2012;7(3):e32745. doi: 10.1371/journal.pone.0032745. Epub 2012 Mar 6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing SCS implanted with Precision SpectraTM in people with Failed Back Surgery Syndrome, run by General University Hospital of Valencia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical decision support system (CDSS) for selection of patients candidates for SCS implant (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04735159, which also lists 29 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2021.