Towards Individualized Deep Brain Stimulation Treatment of Chronic Neuropathic Pain

Neuralgia Clinical Trial

— DBSforPain  

Official title:

Towards Individualized Deep Brain Stimulation Treatment of Chronic Neuropathic Pain

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01899170
• Other study ID #: 28052013
• Secondary ID: 2013-002385-39
• Status: Terminated
• Phase: Phase 2
• Start date: April 1, 2014
• Est. completion date: August 1, 2019

Study information

• Verified date: July 2013
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: August 1, 2019
• Est. primary completion date: August 1, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Neuralgia

Intervention

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.

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

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus	Region Midtjylland

Sponsors (3)

Lead Sponsor	Collaborator
University of Aarhus	California Pacific Medical Center Research Institute, Stanford University

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Effect of transcranial magnetic stimulation on pain ratings, cingulate opioid binding and blood flow	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)
Primary	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.	Assessment after 3 and 12 months of active stimulation
Primary	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.	Assessed upon final evaluation of deep brain stimulation outcome (expected 2 years)
Secondary	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.	After 3 and 12 months of active deep brain stimulation
Secondary	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.	After 3 and 12 months of active deep brain stimulation