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PET Patterns, Biomarkers and Outcome in Burst SCS Treated FBSS Patients (PET-SCS)

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ClinicalTrials.gov Identifier: NCT03419312
Recruitment Status : Recruiting
First Posted : February 1, 2018
Last Update Posted : March 15, 2018
Sponsor:
Collaborators:
Linkoeping University
Boston Children’s Hospital
Information provided by (Responsible Party):
Uppsala University

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).

Condition or disease Intervention/treatment Phase
FBSS Pain, Intractable Low Back Pain Radicular; Neuropathic, Lumbar, Lumbosacral Device: Proclaim™ Elite 5: Burst - Washout - Sham Device: Proclaim™ Elite 5: Sham - Washout - Burst Not Applicable

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
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.

Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:

The stimulation periods with sham stimulation and burst are blinded to all included in the study except SCS nurse 1 who program and reset IPG during study phase 2.

Sham stimulation is achieved by switching of the stimulation equipment in connection with programming prior to the start of the current stimulation period. The programming procedure is identical before burst and sham stimulation periods.

Primary Purpose: Basic Science
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
Actual Study Start Date : February 11, 2018
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019

Arm Intervention/treatment
Experimental: Study sequence A

Proclaim™ Elite 5: Burst - Washout - Sham

  1. 14 days of burst stimulation.
  2. 7 days washout.
  3. 14 days of sham stimulation.
Device: Proclaim™ Elite 5: Burst - Washout - Sham

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.

Other Names:
  • Burst DR
  • Spinal Cord Stimulation

Experimental: Study sequence B

Proclaim™ Elite 5: Sham - Washout - Burst

  1. 14 days of sham stimulation.
  2. 7 days washout.
  3. 14 days of burst stimulation.
Device: Proclaim™ Elite 5: Sham - Washout - Burst

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.

Other Names:
  • Burst DR
  • Spinal Cord Stimulation




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Semiquantitative assessment of protein levels associated with inflammation. [ Time Frame: Measured at day 0 (baseline), day 14, day 21 and day 35. ]
    Level of normalized protein expression (NPX) in plasma, assessed by a multiplex proximity extension assay panel (Olink Bioscience, Uppsala, Sweden).

  2. Back and leg pain [ Time Frame: Measured at visit day 0 (baseline), day 14 and day 35. ]
    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).

  3. General pain [ Time Frame: Measured at day 0 (baseline), day 14 and day 35. ]
    General pain measured by Brief Pain Inventory (BPI) item 3, 4, 5 and 6

  4. Pain inference [ Time Frame: Measured at day 0 (baseline), day 14 and day 35. ]
    Measured by BPI item 9A-9G

  5. Disability [ Time Frame: Measured at day 0 (baseline), day 14 and day 35. ]
    Disability measured by Oswestry Disability Index (ODI).

  6. Pain Catastrophizing [ Time Frame: Measured at day 0 (baseline), day 14 and day 35. ]
    Measured by Pain Catastrophizing Scale (PCS).

  7. Pain Vigilance and Awareness [ Time Frame: Measured at day 0 (baseline), day 14 and day 35. ]
    Measured by the Pain Vigilance and Awareness Questionnaire (PVAQ).

  8. Global Impression of Change [ Time Frame: Measured at day 14 and day 35. ]
    Impression of change in health status assessed by the inventory Patient Global Impression of Change (PGIC).

  9. Depression [ Time Frame: Measured at day 0 (baseline), day 14 and day 35. ]
    Symptoms of depression is assessed by the inventory Patient Health Questionnaire (PHQ-9).

  10. Anxiety [ Time Frame: Measured at day 0 (baseline), day 14 and day 35. ]
    Symptoms of anxiety is assessed by the inventory Generalized Anxiety Disorder Screener (GAD-7).



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Ages Eligible for Study:   18 Years to 59 Years   (Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Gender Eligibility Description:   6 female and 6 male subjects will be included.
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03419312


Contacts
Contact: Terje Kirketeig, MD +46186111110 terje.kirketeig@surgsci.uu.se
Contact: Rolf Karlsten, MD, PhD +46186111110 rolf.karlsten@akademiska.se

Locations
Sweden
Uppsala University Hospital, Uppsala University, Dept. of Surgical Sciences and Dept. of Medicinal Chemistry, Div. of Molecular Imaging. Recruiting
Uppsala, Sweden, 75185
Contact: Rolf Karlsten, MD, PhD    +46186111110    rolf.karlsten@akademiska.se   
Contact: Terje Kirketeig, MD    +46186111110    terje.kirketeig@surgsci.uu.se   
Sub-Investigator: Gunnar Antoni, MD, PhD         
Sub-Investigator: Anders Wåhlstedt, MD         
Sub-Investigator: Mark Lubberink, MD, PhD         
Sub-Investigator: Katarina Landy, MD         
Sub-Investigator: Eva Leljevahl, RN         
Sub-Investigator: Clas Linnman, PhD         
Sub-Investigator: Emmanuel Bäckryd, MD, PhD         
Sub-Investigator: Maria Westerberg, RN         
Sub-Investigator: Marie Essermark, RN         
Sub-Investigator: Torsten Gordh, MD, PhD         
Sponsors and Collaborators
Uppsala University
Linkoeping University
Boston Children’s Hospital
Investigators
Principal Investigator: Rolf Karlsten, MD, PhD rolf.karlsten@akademiska.se

Responsible Party: Uppsala University
ClinicalTrials.gov Identifier: NCT03419312     History of Changes
Other Study ID Numbers: IRB 2017/110/1
First Posted: February 1, 2018    Key Record Dates
Last Update Posted: March 15, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Uppsala University:
Spinal Cord Stimulation
Burst Spinal Cord Stimulation
SCS

Additional relevant MeSH terms:
Back Pain
Low Back Pain
Pain, Intractable
Radiculopathy
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Peripheral Nervous System Diseases
Neuromuscular Diseases