Towards Individualized Deep Brain Stimulation Treatment of Chronic Neuropathic Pain

NCT01899170 | Terminated Phase 2 DMC

• 2 other identifiers: 280520132013-002385-39
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Neuralgia

Keywords

deep brain stimulation; multi-coil transcranial magnetic stimulation; PET-imaging; personalized treatment

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (2)

• Effect of deep brain stimulation on cingulate opioid binding and blood flow.

  After 3 and 12 months of active deep brain stimulation

• Pain relief upon individualized deep brain stimulation

  After 3 and 12 months of active deep brain stimulation

Other Outcomes (1)

• Effect of transcranial magnetic stimulation on pain ratings, cingulate opioid binding and blood flow

  results will be assessed upon final transcranial magnetic stimulation session (last participant/last treatment, average 5 weeks)

Study Arms (3)

Sham-DBS

SHAM COMPARATOR

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

Procedure: Deep brain stimulation; Device: Cervel Neurotech, Multi-coil TMS; Drug: 11C-Carfentanil

Active DBS

ACTIVE COMPARATOR

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

Procedure: Deep brain stimulation; Device: Cervel Neurotech, Multi-coil TMS; Drug: 11C-Carfentanil

TMS and PET imaging

EXPERIMENTAL

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; Drug: 11C-Carfentanil

Interventions

Deep brain stimulation PROCEDURE

Implantation of a deep brain stimulation electrode into pain processing brain areas

Active DBS; Sham-DBS

Cervel Neurotech, Multi-coil TMS DEVICE

Non-invasive selective stimulation of deep brain areas using magnetic fields.

Also known as: TMS

Active DBS; Sham-DBS; TMS and PET imaging

11C-Carfentanil DRUG

PET-radioligand for functional brain imaging to assess opioid binding. The compound is a potent synthetic opioid.

Also known as: 11C-Carfentanyl

Active DBS; Sham-DBS; TMS and PET imaging

Eligibility Criteria

• Age: 25 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Aarhus: lead
• Stanford University: collaborator
• California Pacific Medical Center Research Institute: collaborator

Study Sites (1)

Aarhus University Hospital

Aarhus, Central Jutland, 8000, Denmark

Location

MeSH Terms

Conditions

Neuralgia

Interventions

Deep Brain Stimulation; carfentanil

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Surgical Procedures, Operative

Study Officials

• Jens Christian H Sørensen, MD,PhD,DMSc

  Aarhus University Hospital, Department of Neurosurgery

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2013
• First Posted: July 15, 2013
• Study Start: April 1, 2014
• Primary Completion: August 1, 2019
• Study Completion: August 1, 2019
• Last Updated: September 14, 2021

Record last verified: 2013-07

Locations

DK (1)