Clinical trial NCT01899170: Towards Individualized Deep Brain Stimulation Treatment of Chronic Neuropathic Pain
Official title: Towards Individualized Deep Brain Stimulation Treatment of Chronic Neuropathic Pain
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Neuralgia
Keywords: deep brain stimulation
multi-coil transcranial magnetic stimulation
PET-imaging
personalized treatment
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Stanford University
name: California Pacific Medical Center Research Institute
First posted: 2013-07-15
Enrollment: 3
Sex: ALL
Minimum age (years): 25
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Pain relief upon deep brain stimulation of the dorsal anterior cingulate cortex.
timeFrame: Assessment after 3 and 12 months of active stimulation
measure: Predictive values of PET imaging and transcranial magnetic stimulation on deep brain stimulation outcome
timeFrame: Assessed upon final evaluation of deep brain stimulation outcome (expected 2 years)
Secondary outcomes:
measure: Effect of deep brain stimulation on cingulate opioid binding and blood flow.
timeFrame: After 3 and 12 months of active deep brain stimulation
measure: Pain relief upon individualized deep brain stimulation
timeFrame: After 3 and 12 months of active deep brain stimulation
Other outcomes:
measure: Effect of transcranial magnetic stimulation on pain ratings, cingulate opioid binding and blood flow
timeFrame: results will be assessed upon final transcranial magnetic stimulation session (last participant/last treatment, average 5 weeks)
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
state: Region Midtjylland
Study officials:
affiliation: Aarhus University Hospital, Department of Neurosurgery
name: Jens Christian H Sørensen, MD,PhD,DMSc
role: PRINCIPAL_INVESTIGATOR
References: