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

September 13, 2021 updated by: University of Aarhus
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
3

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • Region Midtjylland
      • Aarhus, Region Midtjylland, Denmark, 8000
        • Aarhus University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

25 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
SHAM_COMPARATOR: Sham-DBS
Only patients. Inactive deep brain stimulation for the initial three months following implantation.
Procedure: Deep brain stimulation
Implantation of a deep brain stimulation electrode into pain processing brain areas
Device: Cervel Neurotech, Multi-coil TMS
Non-invasive selective stimulation of deep brain areas using magnetic fields.
Other Names:
  • TMS
Drug: 11C-Carfentanil
PET-radioligand for functional brain imaging to assess opioid binding. The compound is a potent synthetic opioid.
Other Names:
  • 11C-Carfentanyl
ACTIVE_COMPARATOR: Active DBS
Only patients. Active deep brain stimulation for the initial three months following surgery.
Procedure: Deep brain stimulation
Implantation of a deep brain stimulation electrode into pain processing brain areas
Device: Cervel Neurotech, Multi-coil TMS
Non-invasive selective stimulation of deep brain areas using magnetic fields.
Other Names:
  • TMS
Drug: 11C-Carfentanil
PET-radioligand for functional brain imaging to assess opioid binding. The compound is a potent synthetic opioid.
Other Names:
  • 11C-Carfentanyl
EXPERIMENTAL: TMS and PET imaging
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.
Device: Cervel Neurotech, Multi-coil TMS
Non-invasive selective stimulation of deep brain areas using magnetic fields.
Other Names:
  • TMS
Drug: 11C-Carfentanil
PET-radioligand for functional brain imaging to assess opioid binding. The compound is a potent synthetic opioid.
Other Names:
  • 11C-Carfentanyl

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pain relief upon deep brain stimulation of the dorsal anterior cingulate cortex.
Time Frame: Assessment after 3 and 12 months of active stimulation
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.
Assessment after 3 and 12 months of active stimulation
Predictive values of PET imaging and transcranial magnetic stimulation on deep brain stimulation outcome
Time Frame: Assessed upon final evaluation of deep brain stimulation outcome (expected 2 years)
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.
Assessed upon final evaluation of deep brain stimulation outcome (expected 2 years)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Effect of deep brain stimulation on cingulate opioid binding and blood flow.
Time Frame: After 3 and 12 months of active deep brain stimulation
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.
After 3 and 12 months of active deep brain stimulation
Pain relief upon individualized deep brain stimulation
Time Frame: After 3 and 12 months of active 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.
After 3 and 12 months of active deep brain stimulation

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Effect of transcranial magnetic stimulation on pain ratings, cingulate opioid binding and blood flow
Time Frame: results will be assessed upon final transcranial magnetic stimulation session (last participant/last treatment, average 5 weeks)
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.
results will be assessed upon final transcranial magnetic stimulation session (last participant/last treatment, average 5 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Aarhus

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Stanford University
California Pacific Medical Center Research Institute

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jens Christian H Sørensen, MD,PhD,DMSc, Aarhus University Hospital, Department of Neurosurgery

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2014

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2019

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 3, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 10, 2013

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 15, 2013

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 14, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 13, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 28052013
  • 2013-002385-39 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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