Chronic Pain, Neuropathic Pain
Conditions
Keywords
stereoencephalography, deep brain stimulation, insula, neuromodulation
Brief summary
This study will comprehensively investigate the insula as a brain target for neuromodulation to treat chronic neuropathic pain.
Detailed description
In the first stage, 12 subjects with refractory neuropathic pain will be enrolled to an inpatient clinical trial for insular brain mapping with acute stimulation and neurophysiological brain monitoring. Electrodes for stimulation and recording will be implanted stereotactically along the anterior-posterior axis of the insular cortex. 'Responders' to trial stimulation and the optimal region of the insula for pain relief will be identified during this inpatient stage. 'Responder' subjects who have positive analgesic effects from acute insular stimulation during the first stage will continue to the second stage. The second stage, clinical trial is conducted outpatient and will test chronic deep brain stimulation of the insula. The study design is randomized, sham-stimulation-controlled, double-blinded, and cross-over where subjects receive both active and sham stimulation. Furthermore, neurophysiological biomarkers of pain will be investigated by studying changes in neural activity.
Interventions
DEVICEneuromodulation
During the inpatient phase of the study, insular mapping will be performed with electrical stimulation to implanted SEEG electrodes in order to optimize the region for trial stimulation. Subjects who respond favorably to trial stimulation in the hospital, will progress to the outpatient clinical trial phase where a DBS system will be implanted. All subjects will be blindly randomized to 3 months of stimulation and 3 months of sham stimulation.
Sponsors
Boston Scientific Corporation
University of Virginia
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Participants are blinded to stimulator status in the crossover phase of the study. Primary outcomes are determined by an assessor who is blinded to stimulation status.
Intervention model description
Subjects who respond favorably to trial stimulation of the insula will be enrolled in a crossover study of DBS where they will be randomized to 3 months of active stimulation and 3 months of sham stimulation.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Men and women, between 18 and 80 years, inclusive 2. Subjects who are able and willing to give consent and able to attend all study visits 3. The pain is: * chronic with ≥6 month duration * severe is defined as: 'average' NPRS score of ≥ 5 out of 10 at current visit and the subject reports having a similar level of pain for at least the past two months * disabling and has resulted in an inability to work or perform ADLs in the home * medication-refractory to adequate trials of at least 3 prescription medications (including at least one current or past opioid) commonly used for symptomatic relief of pain. An adequate medication trial is defined as a therapeutic dose of each medication without sufficient effect. * treatment-resistant and cannot be treated or has failed procedures including interventional therapies with injections, spinal neuromodulation with medication infusion or stimulation, and neurosurgical ablation surgery. 4. The pain is neuropathic or predominantly neuropathic if mixed components. * Subject suffering from a pure neuropathic pain syndrome will be included if the pain has resulted from a specific injury including trauma, ischemia, hemorrhage, infection, tumor or iatrogenic to either the peripheral (nerve, spinal root, plexus, cranial nerve) or to the central nervous system (spinal cord or brain) Etiologies include: * Poststroke pain * Thalamic pain * Spinal cord injury * Brachial plexus injury or limb avulsion * Peripheral nerve injury or painful neuropathy * Postherpetic neuralgia, Tolosa Hunt syndrome, or cavernous sinus syndromes * Trigeminal neuropathic pain (not trigeminal neuralgia) 5. Insula region must be apparent on MRI so that direct targeting can be performed for SEEG and DBS electrode placement. 6. Able to communicate and report sensations during all stimulation testing 7. Stable prescribed doses of all symptomatic pain medications for 30 days prior to study entry and for the duration of the study. 8. Inclusion and
Exclusion criteria
have been agreed upon by the principal investigator and the pain psychologist, both of whom have interviewed, examined and if appropriate provided psychotherapeutic intervention to the subject.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | Entire study period from enrollment through 6 months post DBS implantation | Adverse event reporting will be collected throughout the study period. This will include neurological assessments by the study team postoperatively using the NIH Stroke Scale, MR imaging of implanted electrodes, comprehensive assessment of mood and cognition by a licensed psychologist, and vigilance for suicide with the asQ Screening Tool. |
| Pain intensity | Baseline, 3 months post DBS stimulation, 3 months post sham stimulation | The primary efficacy outcome measure compares the change in pain intensity, as rated by the blinded subjects using the Numeric Pain Rating Scale (NPRS), between bilateral DBS of the insula and sham stimulation. The NPRS is an 11 point scale where 0 represents no pain and 10 represents the worst possible pain. Clinical pain severity will be assessed daily in the home environment with a 7-day Ecological Momentary Assessment (NPRS rating) aggregated across days. The analysis will focus on DBS-ON Week 12 data relative to the DBS-OFF (Sham) Week 12 data, controlling for Baseline data. |
Countries
United States
Contacts
Primary ContactJudy Beenhakker
Backup ContactZak Sturgill
Outcome results
None listed