FBSSPET-SCSNCT03419312
PET Patterns, Biomarkers and Outcome in Burst SCS Treated FBSS Patients
A study of FBSS and Pain, Intractable, run by Uppsala University at 1 site in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 59 years
- Conditions the study is for
- FBSS, Pain, Intractable, Low Back Pain
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteSweden
- Study dates
- 11 Feb 2018to Jun 2021
- 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 18 to 59 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Occurrence of chronic pain in the lumbosacral region, as well as unilateral or bilateral leg pain.
- Prior lumbar surgery in medical history.
- 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.
- Patient report largely unchanged pain condition last 6 months.
- Patient has undergone a 7 day SCS trial with epidural burst stimulation with the following results:
- At least 75% coverage of the painful area of tonic stimulation before start of burst trial stimulation.
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- At least 50% reduction in pain intensity, measured via BPI, item 5 from baseline of trial to end of trial period.
- The patient is ≥ 18 years of age and < 60 years of age.
- The patient must willingly participate in all parts of the study, as well as having the ability to complete the entire study plan.
- Patient must certify that he / she understands the study plan, as well as voluntarily sign informed consent to participate in the study.
- Must be able to sit still for a minimum of 45 minutes and be able to follow restrictions related to the PET survey.
Who cannot join
- The patient has other current pain conditions than back and leg pain after back surgery.
- The patient is treated with opioids exceeding 80 milligrams of Morphine per day or is considered at risk for development of problematic opioid use.
- The patient suffers from an untreated depression or anxiety.
- The patient can not complete the study plan.
- The patient is unable to read or write Swedish.
- The patient is currently participates in another clinical trial.
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- A history of previous PET scan or other substantial radiation dose in the last 5 years.
- The patients is suffering from claustrophobia.
- Ongoing pregnancy or planned pregnancy during study time.
- The patient has contraindications for arterial catheterization.
- The patient is previously treated with spinal cord stimulation.
Trial locations and contacts
1 site in 1 country.
Sweden1 site
Uppsala University Hospital, Uppsala University, Dept. of Surgical Sciences and Dept. of Medicinal Chemistry, Div. of Molecular Imaging.
Uppsala, 75185
About this study
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
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).
Read the 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.
- Being tested
- Proclaim™ Elite 5: Burst - Washout - Sham, Proclaim™ Elite 5: Sham - Washout - Burst
- Keywords
- Spinal Cord Stimulation, Burst Spinal Cord Stimulation, SCS
- Medical subject headings
- Pain, Intractable, Low Back Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Proclaim™ Elite 5: Burst - Washout - ShamDevice
Also called Burst DR, Spinal Cord Stimulation
All implanted hardware manufactured by S:t Jude Medical/Abbot:
Implantable Pulse Generator (IPG): Proclaim™ Elite 5 IPG, model 3660. Electrode: Octrode percutaneous lead, 60 cm, model 3161. Anchor: Long lead anchor, model 1106.
Proclaim™ Elite 5: Sham - Washout - BurstDevice
Also called Burst DR, Spinal Cord Stimulation
All implanted hardware manufactured by S:t Jude Medical/Abbot:
Implantable Pulse Generator (IPG): Proclaim™ Elite 5 IPG, model 3660. Electrode: Octrode percutaneous lead, 60 cm, model 3161. Anchor: Long lead anchor, model 1106.
| Study group | Role | What they receive |
|---|---|---|
| Study sequence A | Experimental | Proclaim™ Elite 5: Burst - Washout - Sham
1. 14 days of burst stimulation.
2. 7 days washout.
3. 14 days of sham stimulation. Receives: Device: Proclaim™ Elite 5: Burst - Washout - Sham |
| Study sequence B | Experimental | Proclaim™ Elite 5: Sham - Washout - Burst
1. 14 days of sham stimulation.
2. 7 days washout.
3. 14 days of burst stimulation. Receives: Device: Proclaim™ Elite 5: Sham - Washout - Burst |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in regional cerebral blood flow measured with 15O-water Positron Emission. Tomography (PET)
35 Volume of Interest (VOI) will be applied to each PET scan using the PVElab software. Cerebral blood flow (CBF) and perfusable tissue fraction (PTF) will be calculated for each VOI at each scan. Same tests will be done at voxel level with the Statistical Parameter Mapping Software (SPM12), to identify areas with changed CBF or PTF that do not correspond to VOI in the template.
Measured: PET is performed at study day 0 (baseline), day 14 and day 35.
Secondary outcomes (10)
Semiquantitative assessment of protein levels associated with inflammation.
Level of normalized protein expression (NPX) in plasma, assessed by a multiplex proximity extension assay panel (Olink Bioscience, Uppsala, Sweden).
Measured: Measured at day 0 (baseline), day 14, day 21 and day 35.
Back and leg pain
Measured using a 100mm Visual Analog Scale (VAS) for back and leg pain, respectively. Scale range: 0 mm indicates no pain (minimum), 100 mm indicates worst imaginable pain (maximum).
Measured: Measured at visit day 0 (baseline), day 14 and day 35.
General pain
General pain measured by Brief Pain Inventory (BPI) item 3, 4, 5 and 6
Measured: Measured at day 0 (baseline), day 14 and day 35.
Pain inference
Measured by BPI item 9A-9G
Measured: Measured at day 0 (baseline), day 14 and day 35.
Disability
Disability measured by Oswestry Disability Index (ODI).
Measured: Measured at day 0 (baseline), day 14 and day 35.
Pain Catastrophizing
Measured by Pain Catastrophizing Scale (PCS).
Measured: Measured at day 0 (baseline), day 14 and day 35.
Pain Vigilance and Awareness
Measured by the Pain Vigilance and Awareness Questionnaire (PVAQ).
Measured: Measured at day 0 (baseline), day 14 and day 35.
Global Impression of Change
Impression of change in health status assessed by the inventory Patient Global Impression of Change (PGIC).
Measured: Measured at day 14 and day 35.
Depression
Symptoms of depression is assessed by the inventory Patient Health Questionnaire (PHQ-9).
Measured: Measured at day 0 (baseline), day 14 and day 35.
Anxiety
Symptoms of anxiety is assessed by the inventory Generalized Anxiety Disorder Screener (GAD-7).
Measured: Measured at day 0 (baseline), day 14 and day 35.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2018
- Study start11 Feb 2018
- Primary completionJun 2021 (estimated)
- Study completionJun 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for FBSSStudies of the same condition, open and under way.
- More trials run by Uppsala UniversityThe sponsor's other registered studies.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Uppsala University
- Sponsor type
- University, hospital or other
- Collaborators
- Linkoeping University, Boston Children's Hospital
- Responsible party
- Sponsor
- Investigators
- Rolf Karlsten, MD, PhD, Principal investigator, rolf.karlsten@akademiska.se
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03419312
- Sponsor's protocol ID
- IRB 2017/110/1
- Acronym
- PET-SCS
- Status last verified
- Apr 2020
- First submitted
- 27 Nov 2017
- Last updated
- 8 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 34854473
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03419312
- Acronym / sponsor ID
- PET-SCS / IRB 2017/110/1
- Keywords
- Spinal Cord Stimulation, Burst Spinal Cord Stimulation, SCS
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Uppsala UniversityUniversity, hospital or other
- Collaborators
- Linkoeping University, Boston Children's Hospital
- Study start
- 11 Feb 2018 (actual)
- Primary completion
- Jun 2021 (estimated)
- Study completion
- Jun 2021 (estimated)
- First posted
- 1 Feb 2018 (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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Study sequence A | Experimental | Device: Proclaim™ Elite 5: Burst - Washout - ShamProclaim™ Elite 5: Burst - Washout - Sham 1. 14 days of burst stimulation. 2. 7 days washout. 3. 14 days of sham stimulation. |
| Study sequence B | Experimental | Device: Proclaim™ Elite 5: Sham - Washout - BurstProclaim™ Elite 5: Sham - Washout - Burst 1. 14 days of sham stimulation. 2. 7 days washout. 3. 14 days of burst stimulation. |
Who may qualify
- Ages
- 18 to 59 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Occurrence of chronic pain in the lumbosacral region, as well as unilateral or bilateral leg pain.
- Prior lumbar surgery in medical history.
- 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.
- Patient report largely unchanged pain condition last 6 months.
- Patient has undergone a 7 day SCS trial with epidural burst stimulation with the following results:
Key exclusion criteria (11 listed)
- The patient has other current pain conditions than back and leg pain after back surgery.
- The patient is treated with opioids exceeding 80 milligrams of Morphine per day or is considered at risk for development of problematic opioid use.
- The patient suffers from an untreated depression or anxiety.
- The patient can not complete the study plan.
- The patient is unable to read or write Swedish.
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 |
|---|---|---|
| Proclaim™ Elite 5: Burst - Washout - ShamAlso: Burst DR, Spinal Cord StimulationAll implanted hardware manufactured by S:t Jude Medical/Abbot: Implantable Pulse Generator (IPG): Proclaim™ Elite 5 IPG, model 3660. Electrode: Octrode percutaneous lead, 60 cm, model 3161. Anchor: Long lead anchor, model 1106. | Device | Study sequence A |
| Proclaim™ Elite 5: Sham - Washout - BurstAlso: Burst DR, Spinal Cord StimulationAll implanted hardware manufactured by S:t Jude Medical/Abbot: Implantable Pulse Generator (IPG): Proclaim™ Elite 5 IPG, model 3660. Electrode: Octrode percutaneous lead, 60 cm, model 3161. Anchor: Long lead anchor, model 1106. | Device | Study sequence B |
Primary outcome
Change in regional cerebral blood flow measured with 15O-water Positron Emission. Tomography (PET)
Time frame: PET is performed at study day 0 (baseline), day 14 and day 35.
35 Volume of Interest (VOI) will be applied to each PET scan using the PVElab software. Cerebral blood flow (CBF) and perfusable tissue fraction (PTF) will be calculated for each VOI at each scan. Same tests will be done at voxel level with the Statistical Parameter Mapping Software (SPM12), to identify areas with changed CBF or PTF that do not correspond to VOI in the template.
10 secondary outcomes
Semiquantitative assessment of protein levels associated with inflammation.
Time frame: Measured at day 0 (baseline), day 14, day 21 and day 35.
Back and leg pain
Time frame: Measured at visit day 0 (baseline), day 14 and day 35.
General pain
Time frame: Measured at day 0 (baseline), day 14 and day 35.
Pain inference
Time frame: Measured at day 0 (baseline), day 14 and day 35.
Disability
Time frame: Measured at day 0 (baseline), day 14 and day 35.
Pain Catastrophizing
Time frame: Measured at day 0 (baseline), day 14 and day 35.
Pain Vigilance and Awareness
Time frame: Measured at day 0 (baseline), day 14 and day 35.
Global Impression of Change
Time frame: Measured at day 14 and day 35.
Depression
Time frame: Measured at day 0 (baseline), day 14 and day 35.
Anxiety
Time frame: Measured at day 0 (baseline), day 14 and day 35.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2020.
- Derived from this study: PubMed 34854473O'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.
- Individual participant dataSharing planned: Undecided
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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.
Rolf Karlsten, MD, PhD principal investigator
rolf.karlsten@akademiska.se
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study of FBSS and Pain, Intractable, run by Uppsala University at 1 site in Sweden.
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 11 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 8 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Results are not available in the source record.
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?
Change in regional cerebral blood flow measured with 15O-water Positron Emission. Tomography (PET) (time frame: PET is performed at study day 0 (baseline), day 14 and day 35.). 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 NCT03419312, which also lists 1 linked publication.
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 8 Apr 2020.