Insula Neuromodulation for Chronic Neuropathic Pain

NCT05404581 | Recruiting DMC FDA Device

• 1 other identifier: G200049
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study will comprehensively investigate the insula as a brain target for neuromodulation to treat chronic neuropathic pain.

Conditions

Neuropathic Pain; Chronic Pain

Keywords

stereoencephalography; deep brain stimulation; insula; neuromodulation

Outcome Measures

Primary Outcomes (2)

• Adverse events

  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.

  Entire study period from enrollment through 6 months post DBS implantation

• Pain intensity

  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.

  Baseline, 3 months post DBS stimulation, 3 months post sham stimulation

Study Arms (2)

Control

SHAM COMPARATOR

Subjects who respond favorably to test/trial stimulation of the insula will be implanted with DBS devices. In an outpatient clinical trial, each subject will receive 3 months of active stimulation and 3 months of sham stimulation. The assignment for stimulation will be randomized and blinded to the subject and to the outcome assessors.

Device: neuromodulation

DBS of the insula

ACTIVE COMPARATOR

Subjects who respond favorably to test/trial stimulation of the insula will be implanted with DBS devices. In an outpatient clinical trial, each subject will receive 3 months of active stimulation and 3 months of sham stimulation. The assignment for stimulation will be randomized and blinded to the subject and to the outcome assessors.

Device: neuromodulation

Interventions

neuromodulation DEVICE

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.

Also known as: deep brain stimulation

Control; DBS of the insula

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women, between 18 and 80 years, inclusive
• Subjects who are able and willing to give consent and able to attend all study visits
• 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.
• 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

You may not qualify if:

• Idiopathic pain syndromes will be excluded. Examples include:
• Fibromyalgia syndrome
• temporomandibular joint disorders
• irritable bowel syndrome
• chronic headaches
• interstitial cystitis
• chronic pelvic pain
• whiplash-associated disorders
• Subjects deemed poor candidates by a multidisciplinary team of pain clinicians including specialists in neurosurgery, pain management, and pain psychology:
• Significant clinician concern(s) about reliability of subject-reported information, such as subject in active process of seeking disability for neuropathic pain
• Subjects exhibiting any behavior(s) consistent with ethanol or substance abuse as defined by the criteria outlined in the DSM-V as manifested by one (or more) of the following occurring within a 12 month period: Recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home (such as repeated absences or poor work performance related to substance use; substance-related absences, suspensions, or expulsions from school; or neglect of children or household). Recurrent substance use in situations in which it is physically hazardous (such as driving an automobile or operating a machine when impaired by substance use)
• Recurrent substance-related legal problems (such as arrests for substance related disorderly conduct)
• Continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance (for example, arguments with spouse about consequences of intoxication and physical fights).
• Suspected dementia based on neuropsychological screening or Mini Mental State Exam (MMSE) Score \< 25
• Subjects with active psychiatric illness will be excluded. For the purpose of this study, active psychiatric illness includes:

Sponsors & Collaborators

• University of Virginia: lead
• Boston Scientific Corporation: collaborator

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

Related Publications (1)

• Liu CC, Moosa S, Quigg M, Elias WJ. Anterior insula stimulation increases pain threshold in humans: a pilot study. J Neurosurg. 2021 Apr 2;135(5):1487-1492. doi: 10.3171/2020.10.JNS203323. Print 2021 Nov 1.

  PMID: 33799301 BACKGROUND

MeSH Terms

Conditions

Neuralgia; Chronic Pain

Interventions

Transcutaneous Electric Nerve Stimulation; Deep Brain Stimulation

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; Physical Therapy Modalities; Rehabilitation; Analgesia; Anesthesia and Analgesia; Surgical Procedures, Operative

Study Officials

• Jeff Elias, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Judy Beenhakker

CONTACT

434-982-1856; jgb3p@hscmail.mcc.virginia.edu

Zak Sturgill

CONTACT

434-243-9986; ffm7rc@virginia.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurological Surgery

Model Details: 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.

Study Record Dates

• First Submitted: May 26, 2022
• First Posted: June 3, 2022
• Study Start: November 1, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 29, 2027
• Last Updated: December 10, 2024

Record last verified: 2024-05

Locations

US (1)