Clinical trial NCT02650362: STructural And FunCTional Brain Alterations by HIgh FrequenCy Spinal Cord Stimulation
Official title: STructural And FunCTional Brain Alterations by HIgh FrequenCy Spinal Cord Stimulation: a Combined Voxel-based Morphometry and Resting State Functional Connectivity Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Failed Back Surgery Syndrome
Keywords: spinal cord stimulation
resting state functional magnetic resonance
voxel-based magnetic resonance morphometry
Lead sponsor: Universitair Ziekenhuis Brussel
Sponsor class: OTHER
Collaborators: name: Nevro
First posted: 2016-01-08
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is an interventional prospective observatory single center trial, investigating the supraspinal effects of long term paresthesia-free high frequency SCS in FBSS patients with back and leg pain completed with resting state functional magnetic resonance (rs fMRI) and voxel-based magnetic resonance morphometry (VBM).

Detailed description: When patient meets all inclusion criteria and no exclusion criteria, a neuroimaging protocol will be obtained at baseline, prior to trial implantation of SCS.

Normal trial period will be respected based on the reimbursement rules in Belgium (4 weeks). When the patient is eligible for implantation of the definitive SCS system (more than 50% pain reduction and/or more than 50% reduction in pain medication), patient will undergo surgery for definitive implantation.

After stabilisation of the stimulation parameters at least for more than 1 month, the second session of neuroimaging will occur (T1). Minimal one month later (2 months after implantation of definitive SCS system) the patient will undergo the last session of neuroimaging (T2). The MRI protocol will occur after stabilisation of the stimulation parameters at least for more than 1 month. During the whole period, patients will fill in a VAS diary and at time of neuroimaging T1 and T2 a Likert-scale in order to evaluate the satisfaction grade of the patient. Additionally, patients will also wear 1 month before neuroimaging an Actiwatch, measuring sleep patterns and filling in questionnaires at baseline, T1 and T2 (Pittsburgh Sleep Quality Index (PSQI).

Eligibility criteria: Inclusion Criteria:

* Subject is at least 18 years old.
* Subject is able and willing to comply with the follow-up schedule and protocol
* Diagnosis of FBSS with predominant back pain (visual analogue scale (VAS) \> 5).
* Cognitive and language functioning enabling coherent communication between the examiner and the subject;
* Failed conservative treatments for pain including but not limited to pharmacological therapy and physical therapy
* Stable neurologic function in the past 30 days
* In the opinion of the Investigator, the subject is psychologically appropriate for the implantation for an active implantable medical device
* Subject is able to provide written informed consent
* Subject speaks Dutch or French.

Exclusion Criteria:

* Female subject of childbearing potential is pregnant/nursing, or plans to become pregnant during the course of the trial
* Subject has had radiofrequency treatment of an intended target DRG within the past 3 months
* Subject currently has an active implantable device including ICD, pacemaker, spinal cord stimulator, deep brain stimulator or intrathecal drug pump
* Subject is unable to operate the device or has no relative available.
* Subjects with indwelling devices that may pose an increased risk of infection
* Subject currently has an active infection
* Subject has, in the opinion of the Investigator, a medical comorbidity that contraindicates placement of an active medical device
* Subject has participated in another clinical investigation within 30 days
* Subject has a coagulation disorder or uses anticoagulants that, in the opinion of the investigator, precludes participation
* Subject has been diagnosed with cancer in the past 2 years
* Life expectancy \< 6 months
* Imaging (MRI, CT, x-ray) findings within the last 12 months that, in the Investigator's opinion, contraindicates lead placement
* Existing extreme fear for entering MRI
* General contraindication for MRI (pacemaker, etc...)
* Age male/female patient \<18 years

Primary outcomes:
measure: Grey Mater Volume assessed by Voxel-based morphometry analysis (based on MRI images)
timeFrame: The change between baseline and 1 month after definitive implantation (T1) and the change between baseline and 2 months after definitive implantation (T2).
measure: Functional connectivity analysis using in-house developed software (based on MRI images)
timeFrame: The change between baseline and 1 month after definitive implantation (T1) and the change between baseline and 2 months after definitive implantation (T2).
Secondary outcomes:
measure: Visual Analogue Scale (VAS) pain diary
timeFrame: Three times every day (morning, afternoon and evening), starting 1 week before baseline measurements up to 2 months until study completion
measure: Objective sleep quality will be measured using the Actiwatch spectrum plus (Respironics)
timeFrame: The change between baseline and 1 month after definitive implantation (T1) and the change between baseline and 2 months after definitive implantation (T2).
measure: Subjective sleep quality will be measured by the Pittsburgh Sleep Quality Index (PSQI)
timeFrame: The change between baseline and 1 month after definitive implantation (T1) and the change between baseline and 2 months after definitive implantation (T2).
measure: Pain catastrophizing is assessed by the Pain Catastrophizing Scale (PCS)
timeFrame: The change between baseline and 1 month after definitive implantation (T1) and the change between baseline and 2 months after definitive implantation (T2).
measure: Likert-scale in order to evaluate the satisfaction grade of the patient.
timeFrame: The change between baseline and 1 month after definitive implantation (T1) and the change between baseline and 2 months after definitive implantation (T2).
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: UZ Brussel
state: Vlaams Brabant
Study officials:
References:
citation: Al-Kaisy A, Palmisani S, Smith T, Harris S, Pang D. The use of 10-kilohertz spinal cord stimulation in a cohort of patients with chronic neuropathic limb pain refractory to medical management. Neuromodulation. 2015 Jan;18(1):18-23; discussion 23. doi: 10.1111/ner.12237. Epub 2014 Sep 25.
citation: Deer T, Pope J, Hayek S, Narouze S, Patil P, Foreman R, Sharan A, Levy R. Neurostimulation for the treatment of axial back pain: a review of mechanisms, techniques, outcomes, and future advances. Neuromodulation. 2014 Oct;17 Suppl 2:52-68. doi: 10.1111/j.1525-1403.2012.00530.x.
citation: Al-Kaisy A, Van Buyten JP, Smet I, Palmisani S, Pang D, Smith T. Sustained effectiveness of 10 kHz high-frequency spinal cord stimulation for patients with chronic, low back pain: 24-month results of a prospective multicenter study. Pain Med. 2014 Mar;15(3):347-54. doi: 10.1111/pme.12294. Epub 2013 Dec 5.
citation: Rasche D, Siebert S, Stippich C, Kress B, Nennig E, Sartor K, Tronnier VM. [Spinal cord stimulation in Failed-Back-Surgery-Syndrome. Preliminary study for the evaluation of therapy by functional magnetic resonance imaging (fMRI)]. Schmerz. 2005 Nov;19(6):497-500, 502-5. doi: 10.1007/s00482-005-0388-9. German.
citation: Stancak A, Kozak J, Vrba I, Tintera J, Vrana J, Polacek H, Stancak M. Functional magnetic resonance imaging of cerebral activation during spinal cord stimulation in failed back surgery syndrome patients. Eur J Pain. 2008 Feb;12(2):137-48. doi: 10.1016/j.ejpain.2007.03.003. Epub 2007 Oct 30.
citation: Moens M, Sunaert S, Marien P, Brouns R, De Smedt A, Droogmans S, Van Schuerbeek P, Peeters R, Poelaert J, Nuttin B. Spinal cord stimulation modulates cerebral function: an fMRI study. Neuroradiology. 2012 Dec;54(12):1399-407. doi: 10.1007/s00234-012-1087-8. Epub 2012 Sep 2.
citation: Moens M, Droogmans S, Spapen H, De Smedt A, Brouns R, Van Schuerbeek P, Luypaert R, Poelaert J, Nuttin B. Feasibility of cerebral magnetic resonance imaging in patients with externalised spinal cord stimulator. Clin Neurol Neurosurg. 2012 Feb;114(2):135-41. doi: 10.1016/j.clineuro.2011.09.013. Epub 2011 Oct 22.
citation: Moens M, Marien P, Brouns R, Poelaert J, De Smedt A, Buyl R, Droogmans S, Van Schuerbeek P, Sunaert S, Nuttin B. Spinal cord stimulation modulates cerebral neurobiology: a proton magnetic resonance spectroscopy study. Neuroradiology. 2013 Aug;55(8):1039-1047. doi: 10.1007/s00234-013-1200-7. Epub 2013 May 12.