Clinical trial NCT03419312: PET Patterns, Biomarkers and Outcome in Burst SCS Treated FBSS Patients
Official title: Cerebral PET Patterns, Inflammatory Biomarkers and Outcome in Patients Treated With Burst Spinal Cord Stimulation for Chronic Low Back and Leg Pain: A Randomized Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: FBSS
Pain, Intractable
Low Back Pain
Radicular; Neuropathic, Lumbar, Lumbosacral
Keywords: Spinal Cord Stimulation
Burst Spinal Cord Stimulation
SCS
Lead sponsor: Uppsala University
Sponsor class: OTHER
Collaborators: name: Linkoeping University
name: Boston Children's Hospital
First posted: 2018-02-01
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Patients are randomized to 1 of 2 different treatment sequences:

Sequence A: Active burst stimulation followed by sham stimulation. Sequence B: Sham stimulation followed by burst stimulation. Sham and burst stimulation are separated by 7 days washout.
Primary purpose: BASIC_SCIENCE

Brief summary: The primary aim of this study is to investigate cerebral mechanisms of burst stimulation in Failed Back Surgery Syndrome (FBSS) patients treated with Burst Spinal Cord Stimulation (SCS) for chronic back and leg pain. This study is a single center, prospective, blinded, randomized crossover trial with two 14 days treatment periods and two treatment arms (burst before sham stimulation or sham before burst stimulation).

Detailed description: Background and rationale:

Tonic spinal cord stimulation for chronic primarily neuropathic pain har been used for over 50 years. Tonic stimulation in frequencies from 20 to 70 Hz produces analgesia and paresthesia in the targeted area.

Burst stimulation, a novel spinal cord stimulation pattern, is an intermittent high frequency parenthesis-free therapy. This stimulation pattern consist of 5 spikes with an inter-spike frequency of 500 Hz, delivered at 40 Hz.

Clinical effectiveness and noninferiority of Burst stimulation has been proved. A few studies suggest that Burst stimulation induce different activities in cerebral pathways, compared with tonic stimulation. Patient reported attention to pain assessed by the pain vigilance and awareness questionnaire (PVAQ) seems to differ between burst and tonic spinal cord stimulation. This trial is designed to investigate cerebral mechanisms of burst stimulation, using PET O15-water measured blood flow and tissue perfusion as a proxy for cerebral activity.

Key events in study implementation:

Study phase 1

* Study Inclusion and baseline visit.
* Implantation of spinal cord stimulation system.

Study phase 2:

* Study visit 1(study day 0): Collection of Patient Reported Outcome Measurements (PROM) data, Randomization to study sequence, blood sampling, PET 0, programming of SCS-system.
* Study visit 2 (study day 14): Blood sampling, PET 1, collection of PROM-data, SCS system switched off for washout.
* Study visit 3 (study day 21): Collection of PROM-data, programming of SCS-system, blood sampling.
* Study visit 4 (study day 35): Blood sampling, PET 2, collection of PROM-data, programming of SCS-system.

Eligibility criteria: Inclusion Criteria:

1. Occurrence of chronic pain in the lumbosacral region, as well as unilateral or bilateral leg pain.
2. Prior lumbar surgery in medical history.
3. Diagnosed with neuropathic pain in the lower extremities and graded as probable neuropathic pain or definite neuropathic pain according International Association for the Study of Pain (IASP) criteria.
4. Patient report largely unchanged pain condition last 6 months.
5. Patient has undergone a 7 day SCS trial with epidural burst stimulation with the following results:

   1. At least 75% coverage of the painful area of tonic stimulation before start of burst trial stimulation.
   2. At least 50% reduction in pain intensity, measured via BPI, item 5 from baseline of trial to end of trial period.
6. The patient is ≥ 18 years of age and \< 60 years of age.
7. The patient must willingly participate in all parts of the study, as well as having the ability to complete the entire study plan.
8. Patient must certify that he / she understands the study plan, as well as voluntarily sign informed consent to participate in the study.
9. Must be able to sit still for a minimum of 45 minutes and be able to follow restrictions related to the PET survey.

Exclusion Criteria:

1. The patient has other current pain conditions than back and leg pain after back surgery.
2. The patient is treated with opioids exceeding 80 milligrams of Morphine per day or is considered at risk for development of problematic opioid use.
3. The patient suffers from an untreated depression or anxiety.
4. The patient can not complete the study plan.
5. The patient is unable to read or write Swedish.
6. The patient is currently participates in another clinical trial.
7. A history of previous PET scan or other substantial radiation dose in the last 5 years.
8. The patients is suffering from claustrophobia.
9. Ongoing pregnancy or planned pregnancy during study time.
10. The patient has contraindications for arterial catheterization.
11. The patient is previously treated with spinal cord stimulation.

Primary outcomes:
measure: Change in regional cerebral blood flow measured with 15O-water Positron Emission. Tomography (PET)
timeFrame: PET is performed at study day 0 (baseline), day 14 and day 35.
Secondary outcomes:
measure: Semiquantitative assessment of protein levels associated with inflammation.
timeFrame: Measured at day 0 (baseline), day 14, day 21 and day 35.
measure: Back and leg pain
timeFrame: Measured at visit day 0 (baseline), day 14 and day 35.
measure: General pain
timeFrame: Measured at day 0 (baseline), day 14 and day 35.
measure: Pain inference
timeFrame: Measured at day 0 (baseline), day 14 and day 35.
measure: Disability
timeFrame: Measured at day 0 (baseline), day 14 and day 35.
measure: Pain Catastrophizing
timeFrame: Measured at day 0 (baseline), day 14 and day 35.
measure: Pain Vigilance and Awareness
timeFrame: Measured at day 0 (baseline), day 14 and day 35.
measure: Global Impression of Change
timeFrame: Measured at day 14 and day 35.
measure: Depression
timeFrame: Measured at day 0 (baseline), day 14 and day 35.
measure: Anxiety
timeFrame: Measured at day 0 (baseline), day 14 and day 35.
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Uppsala University Hospital, Uppsala University, Dept. of Surgical Sciences and Dept. of Medicinal Chemistry, Div. of Molecular Imaging.
Study officials:
affiliation: rolf.karlsten@akademiska.se
name: Rolf Karlsten, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: O'Connell NE, Ferraro MC, Gibson W, Rice AS, Vase L, Coyle D, Eccleston C. Implanted spinal neuromodulation interventions for chronic pain in adults. Cochrane Database Syst Rev. 2021 Dec 2;12(12):CD013756. doi: 10.1002/14651858.CD013756.pub2.