Back to results

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

Primary Purpose

FBSS, Pain, Intractable, Low Back Pain

Status

Unknown status

Phase

Not Applicable

Locations

Sweden

Study Type

Interventional

Intervention

Proclaim™ Elite 5: Burst - Washout - Sham

Proclaim™ Elite 5: Sham - Washout - Burst

About this trial

This is an interventional basic science trial for FBSS focused on measuring Spinal Cord Stimulation, Burst Spinal Cord Stimulation, SCS

Eligibility Criteria

18 Years - 59 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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:
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.
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.

Exclusion Criteria:

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.
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.

Sites / Locations

Uppsala University Hospital, Uppsala University, Dept. of Surgical Sciences and Dept. of Medicinal Chemistry, Div. of Molecular Imaging.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Study sequence A

Study sequence B

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).

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).

General pain

General pain measured by Brief Pain Inventory (BPI) item 3, 4, 5 and 6

Pain inference

Measured by BPI item 9A-9G

Disability

Disability measured by Oswestry Disability Index (ODI).

Pain Catastrophizing

Measured by Pain Catastrophizing Scale (PCS).

Pain Vigilance and Awareness

Measured by the Pain Vigilance and Awareness Questionnaire (PVAQ).

Global Impression of Change

Impression of change in health status assessed by the inventory Patient Global Impression of Change (PGIC).

Depression

Symptoms of depression is assessed by the inventory Patient Health Questionnaire (PHQ-9).

Anxiety

Symptoms of anxiety is assessed by the inventory Generalized Anxiety Disorder Screener (GAD-7).

Full Information

NCT ID

NCT03419312

First Posted

November 27, 2017

Last Updated

April 7, 2020

Sponsor

Uppsala University

Collaborators

Linkoeping University, Boston Children's Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03419312

Brief Title

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

Acronym

PET-SCS

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

2. Study Status

Record Verification Date

April 2020

Overall Recruitment Status

Unknown status

Study Start Date

February 11, 2018 (Actual)

Primary Completion Date

June 2021 (Anticipated)

Study Completion Date

June 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Uppsala University

Collaborators

Linkoeping University, Boston Children's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

FBSS, Pain, Intractable, Low Back Pain, Radicular; Neuropathic, Lumbar, Lumbosacral

Keywords

Spinal Cord Stimulation, Burst Spinal Cord Stimulation, SCS

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

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

ParticipantInvestigatorOutcomes 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.

Allocation

Randomized

Enrollment

12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Study sequence A

Arm Type

Experimental

Arm Description

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

Arm Title

Study sequence B

Arm Type

Experimental

Arm Description

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

Intervention Type

Device

Intervention Name(s)

Proclaim™ Elite 5: Burst - Washout - Sham

Other Intervention Name(s)

Burst DR, Spinal Cord Stimulation

Intervention Description

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.

Intervention Type

Device

Intervention Name(s)

Proclaim™ Elite 5: Sham - Washout - Burst

Other Intervention Name(s)

Burst DR, Spinal Cord Stimulation

Intervention Description

Primary Outcome Measure Information:

Title

Change in regional cerebral blood flow measured with 15O-water Positron Emission. Tomography (PET)

Description

Time Frame

PET is performed at study day 0 (baseline), day 14 and day 35.

Secondary Outcome Measure Information:

Title

Semiquantitative assessment of protein levels associated with inflammation.

Description

Level of normalized protein expression (NPX) in plasma, assessed by a multiplex proximity extension assay panel (Olink Bioscience, Uppsala, Sweden).

Time Frame

Measured at day 0 (baseline), day 14, day 21 and day 35.

Title

Back and leg pain

Description

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).

Time Frame

Measured at visit day 0 (baseline), day 14 and day 35.

Title

General pain

Description

General pain measured by Brief Pain Inventory (BPI) item 3, 4, 5 and 6

Time Frame

Measured at day 0 (baseline), day 14 and day 35.

Title

Pain inference

Description

Measured by BPI item 9A-9G

Time Frame

Measured at day 0 (baseline), day 14 and day 35.

Title

Disability

Description

Disability measured by Oswestry Disability Index (ODI).

Time Frame

Measured at day 0 (baseline), day 14 and day 35.

Title

Pain Catastrophizing

Description

Measured by Pain Catastrophizing Scale (PCS).

Time Frame

Measured at day 0 (baseline), day 14 and day 35.

Title

Pain Vigilance and Awareness

Description

Measured by the Pain Vigilance and Awareness Questionnaire (PVAQ).

Time Frame

Measured at day 0 (baseline), day 14 and day 35.

Title

Global Impression of Change

Description

Impression of change in health status assessed by the inventory Patient Global Impression of Change (PGIC).

Time Frame

Measured at day 14 and day 35.

Title

Depression

Description

Symptoms of depression is assessed by the inventory Patient Health Questionnaire (PHQ-9).

Time Frame

Measured at day 0 (baseline), day 14 and day 35.

Title

Anxiety

Description

Symptoms of anxiety is assessed by the inventory Generalized Anxiety Disorder Screener (GAD-7).

Time Frame

Measured at day 0 (baseline), day 14 and day 35.

10. Eligibility

Sex

All

Gender Based

Yes

Gender Eligibility Description

6 female and 6 male subjects will be included.

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

59 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. 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. Exclusion Criteria: 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. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Rolf Karlsten, MD, PhD

Organizational Affiliation

rolf.karlsten@akademiska.se

Official's Role

Principal Investigator

Facility Information:

Facility Name

Uppsala University Hospital, Uppsala University, Dept. of Surgical Sciences and Dept. of Medicinal Chemistry, Div. of Molecular Imaging.

City

Uppsala

ZIP/Postal Code

75185

Country

Sweden

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

34854473

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.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs