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Towards Individualized Deep Brain Stimulation Treatment of Chronic Neuropathic Pain (DBSforPain)

Primary Purpose

Neuralgia

Status
Terminated
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Deep brain stimulation
Cervel Neurotech, Multi-coil TMS
11C-Carfentanil
Sponsored by
University of Aarhus
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuralgia focused on measuring deep brain stimulation, multi-coil transcranial magnetic stimulation, PET-imaging, personalized treatment

Eligibility Criteria

25 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

General inclusion criteria (case and control):

  • No gender criteria
  • Age > 25 years.
  • Legal competency.
  • Ability to comply with the proposed protocol schedule.
  • Stability of chronic medical diseases.
  • A negative validated pregnancy test for fertile female participants prior to project enrolment.
  • Use of validated anti-conception for fertile female participants

Case-specific inclusion criteria:

  • Well-defined neuropathic pain [21].
  • Chronic and stable pain condition. Numerical Rating Scale score > 5.
  • Documented resistance to, or poor tolerance of pharmacological treatments. Unless contraindicated, the treatment must have included opiate derivatives, tri-cyclic antidepressants and anti-epileptic drugs.

Exclusion Criteria:

General exclusion criteria:

  • Pregnancy or nursing.
  • Cognitive impairment.
  • Alcohol or drug abuse
  • Severe psychiatric disorders.
  • Allergies towards compounds used in the trial, such as PET tracers, Capsaicin, etc. Other significant medical allergies.
  • Severe medical disorders
  • Neurodegenerative disorders
  • Severe cerebrovascular diseases and risk-factors, malignant hypertension, vascular abnormalities.
  • Prior intracranial surgery
  • Cardiac pacemaker or other implanted electronic medical devices
  • Coagulopathy (excl. drug induced)
  • Structural brain abnormalities
  • Epilepsy or prior isolated seizure.
  • Severe obesity
  • Severe claustrophobia
  • Magnetic metallic implants
  • Other conditions that may contraindicate deep brain stimulation surgery, full anesthesia, transcranial magnetic stimulation, PET/CT imaging (specifically the use of carfentanil) or magnetic resonance imaging. This will be evaluated according to specific investigational product specifications and clinical guidelines.

Control specific exclusion criteria:

- Chronic pain syndrome

Sites / Locations

  • Aarhus University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Sham Comparator

Active Comparator

Experimental

Arm Label

Sham-DBS

Active DBS

TMS and PET imaging

Arm Description

Only patients. Inactive deep brain stimulation for the initial three months following implantation.

Only patients. Active deep brain stimulation for the initial three months following surgery.

This experiment includes all participants (cases and controls). Each subject will undergo both active and sham stimulation (cross-over) with Cervel Neurotech Multi-coil TMS and related test/re-test PET imaging with 11C-Carfentanil. Only patients will proceed into deep brain stimulation experiments.

Outcomes

Primary Outcome Measures

Pain relief upon deep brain stimulation of the dorsal anterior cingulate cortex.
We will measure the changes in pain ratings upon deep brain stimulation of the dorsal anterior cingulate gyrus. Results will be based on the numerical rating scale and validated questionnaires. We will compare active and sham stimulation and changes upon activation of initial sham-stimulation.
Predictive values of PET imaging and transcranial magnetic stimulation on deep brain stimulation outcome
Individuals will be classified according to PET activity/no-activity and positive/null-negative outcome of transcranial magnetic stimulation. We will correlate the effect of deep brian stimulation to these categories and evaluate their predictive values.

Secondary Outcome Measures

Effect of deep brain stimulation on cingulate opioid binding and blood flow.
We will do test/re-test PET imaging before and after deep brain stimulation surgery to assess the effect of this treatment on cingulate opioid binding and blood flow. We will utilize 11C-Carfentanil and 15O-water PET, respectively.
Pain relief upon individualized deep brain stimulation
Patients that derive no benefit from initial deep brain stimulation treatment of the dorsal anterior cingulate, will be offered deep brain stimulation of another expectedly efficacious brain area. The choice of target will be based of PET images and magnetic stimulation testing. Results of deep brain stimulation will be based on the numerical rating scale and validated pain questionnaires.

Full Information

First Posted
July 3, 2013
Last Updated
September 13, 2021
Sponsor
University of Aarhus
Collaborators
Stanford University, California Pacific Medical Center Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT01899170
Brief Title
Towards Individualized Deep Brain Stimulation Treatment of Chronic Neuropathic Pain
Acronym
DBSforPain
Official Title
Towards Individualized Deep Brain Stimulation Treatment of Chronic Neuropathic Pain
Study Type
Interventional

2. Study Status

Record Verification Date
July 2013
Overall Recruitment Status
Terminated
Why Stopped
Device for multi coil TMS no longer supported
Study Start Date
April 1, 2014 (Actual)
Primary Completion Date
August 1, 2019 (Actual)
Study Completion Date
August 1, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Aarhus
Collaborators
Stanford University, California Pacific Medical Center Research Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Chronic neuropathic pain affects millions of individuals worldwide. It causes marked reduction of health, utility and quality of life and represents a considerable economic burden to society due to loss of work capacity and large treatment expenses. The proposed project will explore new and rational methods for deep brain stimulation treatment of patients with severe chronic neuropathic pain, resistant to conventional treatment. Deep brain stimulation is a neurosurgical procedure in which a small stimulating electrode is implanted into deep brain areas. Furthermore, we will utilize new positron emission tomography neuroimaging and a new prototyped technology, called targeted transcranial magnetic stimulation, to predict the outcome of deep brain stimulation and localize brain regions with maximum symptom relief for each patient. This will optimize the selection of patients for deep brain stimulation and provide a rational customized choice of brain target for each patient, without surgical intervention. Novel techniques will be validated on healthy volunteers and at the same time provide new insights into the mechanisms underlying brain stimulation and pain perception. The project has great clinical impact, potential for innovative development and industrial spin-out, facilitates exchange for Danish research talents and senior researchers with Stanford University and California Pacific Medical Research Institute in San Francisco, and unites world leading experts in pain research and clinical treatment to achieve its goals.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuralgia
Keywords
deep brain stimulation, multi-coil transcranial magnetic stimulation, PET-imaging, personalized treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sham-DBS
Arm Type
Sham Comparator
Arm Description
Only patients. Inactive deep brain stimulation for the initial three months following implantation.
Arm Title
Active DBS
Arm Type
Active Comparator
Arm Description
Only patients. Active deep brain stimulation for the initial three months following surgery.
Arm Title
TMS and PET imaging
Arm Type
Experimental
Arm Description
This experiment includes all participants (cases and controls). Each subject will undergo both active and sham stimulation (cross-over) with Cervel Neurotech Multi-coil TMS and related test/re-test PET imaging with 11C-Carfentanil. Only patients will proceed into deep brain stimulation experiments.
Intervention Type
Procedure
Intervention Name(s)
Deep brain stimulation
Intervention Description
Implantation of a deep brain stimulation electrode into pain processing brain areas
Intervention Type
Device
Intervention Name(s)
Cervel Neurotech, Multi-coil TMS
Other Intervention Name(s)
TMS
Intervention Description
Non-invasive selective stimulation of deep brain areas using magnetic fields.
Intervention Type
Drug
Intervention Name(s)
11C-Carfentanil
Other Intervention Name(s)
11C-Carfentanyl
Intervention Description
PET-radioligand for functional brain imaging to assess opioid binding. The compound is a potent synthetic opioid.
Primary Outcome Measure Information:
Title
Pain relief upon deep brain stimulation of the dorsal anterior cingulate cortex.
Description
We will measure the changes in pain ratings upon deep brain stimulation of the dorsal anterior cingulate gyrus. Results will be based on the numerical rating scale and validated questionnaires. We will compare active and sham stimulation and changes upon activation of initial sham-stimulation.
Time Frame
Assessment after 3 and 12 months of active stimulation
Title
Predictive values of PET imaging and transcranial magnetic stimulation on deep brain stimulation outcome
Description
Individuals will be classified according to PET activity/no-activity and positive/null-negative outcome of transcranial magnetic stimulation. We will correlate the effect of deep brian stimulation to these categories and evaluate their predictive values.
Time Frame
Assessed upon final evaluation of deep brain stimulation outcome (expected 2 years)
Secondary Outcome Measure Information:
Title
Effect of deep brain stimulation on cingulate opioid binding and blood flow.
Description
We will do test/re-test PET imaging before and after deep brain stimulation surgery to assess the effect of this treatment on cingulate opioid binding and blood flow. We will utilize 11C-Carfentanil and 15O-water PET, respectively.
Time Frame
After 3 and 12 months of active deep brain stimulation
Title
Pain relief upon individualized deep brain stimulation
Description
Patients that derive no benefit from initial deep brain stimulation treatment of the dorsal anterior cingulate, will be offered deep brain stimulation of another expectedly efficacious brain area. The choice of target will be based of PET images and magnetic stimulation testing. Results of deep brain stimulation will be based on the numerical rating scale and validated pain questionnaires.
Time Frame
After 3 and 12 months of active deep brain stimulation
Other Pre-specified Outcome Measures:
Title
Effect of transcranial magnetic stimulation on pain ratings, cingulate opioid binding and blood flow
Description
We will do test/re-test PET imaging with transcranial magnetic stimulation in between. We will evaluate quantitative effects on 1) pain ratings using the numerical rating scale, 2) cingulate opioid binding using 11C-carfentanil PET and 3) cingulate blood flow using 15O-water PET. Results will be compared for sham stimulation and active stimulation in each individual, and also between cases and controls.
Time Frame
results will be assessed upon final transcranial magnetic stimulation session (last participant/last treatment, average 5 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: General inclusion criteria (case and control): No gender criteria Age > 25 years. Legal competency. Ability to comply with the proposed protocol schedule. Stability of chronic medical diseases. A negative validated pregnancy test for fertile female participants prior to project enrolment. Use of validated anti-conception for fertile female participants Case-specific inclusion criteria: Well-defined neuropathic pain [21]. Chronic and stable pain condition. Numerical Rating Scale score > 5. Documented resistance to, or poor tolerance of pharmacological treatments. Unless contraindicated, the treatment must have included opiate derivatives, tri-cyclic antidepressants and anti-epileptic drugs. Exclusion Criteria: General exclusion criteria: Pregnancy or nursing. Cognitive impairment. Alcohol or drug abuse Severe psychiatric disorders. Allergies towards compounds used in the trial, such as PET tracers, Capsaicin, etc. Other significant medical allergies. Severe medical disorders Neurodegenerative disorders Severe cerebrovascular diseases and risk-factors, malignant hypertension, vascular abnormalities. Prior intracranial surgery Cardiac pacemaker or other implanted electronic medical devices Coagulopathy (excl. drug induced) Structural brain abnormalities Epilepsy or prior isolated seizure. Severe obesity Severe claustrophobia Magnetic metallic implants Other conditions that may contraindicate deep brain stimulation surgery, full anesthesia, transcranial magnetic stimulation, PET/CT imaging (specifically the use of carfentanil) or magnetic resonance imaging. This will be evaluated according to specific investigational product specifications and clinical guidelines. Control specific exclusion criteria: - Chronic pain syndrome
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jens Christian H Sørensen, MD,PhD,DMSc
Organizational Affiliation
Aarhus University Hospital, Department of Neurosurgery
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aarhus University Hospital
City
Aarhus
State/Province
Region Midtjylland
ZIP/Postal Code
8000
Country
Denmark

12. IPD Sharing Statement

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Towards Individualized Deep Brain Stimulation Treatment of Chronic Neuropathic Pain

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