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

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ClinicalTrials.gov Identifier: NCT01899170
Recruitment Status : Suspended (Device for multi coil TMS no longer supported)
First Posted : July 15, 2013
Last Update Posted : August 23, 2016
Sponsor:
Collaborators:
Stanford University
California Pacific Medical Center Research Institute
Information provided by (Responsible Party):
University of Aarhus

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.

Condition or disease Intervention/treatment Phase
Neuralgia Procedure: Deep brain stimulation Device: Cervel Neurotech, Multi-coil TMS Drug: 11C-Carfentanil Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Towards Individualized Deep Brain Stimulation Treatment of Chronic Neuropathic Pain
Study Start Date : April 2014
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2022

Arm Intervention/treatment
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 Name: TMS

Drug: 11C-Carfentanil
PET-radioligand for functional brain imaging to assess opioid binding. The compound is a potent synthetic opioid.
Other Name: 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 Name: TMS

Drug: 11C-Carfentanil
PET-radioligand for functional brain imaging to assess opioid binding. The compound is a potent synthetic opioid.
Other Name: 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 Name: TMS

Drug: 11C-Carfentanil
PET-radioligand for functional brain imaging to assess opioid binding. The compound is a potent synthetic opioid.
Other Name: 11C-Carfentanyl




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.


Other Outcome Measures:
  1. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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


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): NCT01899170


Locations
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Denmark
Aarhus University Hospital
Aarhus, Region Midtjylland, Denmark, 8000
Sponsors and Collaborators
University of Aarhus
Stanford University
California Pacific Medical Center Research Institute
Investigators
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Principal Investigator: Jens Christian H Sørensen, MD,PhD,DMSc Aarhus University Hospital, Department of Neurosurgery

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Responsible Party: University of Aarhus
ClinicalTrials.gov Identifier: NCT01899170     History of Changes
Other Study ID Numbers: 28052013
2013-002385-39 ( EudraCT Number )
First Posted: July 15, 2013    Key Record Dates
Last Update Posted: August 23, 2016
Last Verified: July 2013

Keywords provided by University of Aarhus:
deep brain stimulation
multi-coil transcranial magnetic stimulation
PET-imaging
personalized treatment

Additional relevant MeSH terms:
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Neuralgia
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Pain
Neurologic Manifestations
Signs and Symptoms
Carfentanil
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents