RECRUITING

Insula Neuromodulation for Chronic Neuropathic Pain

Conditions

Neuropathic Pain Chronic Pain stereoencephalography deep brain stimulation insula neuromodulation

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

A Staged, Comprehensive Investigation of Insular Neuromodulation for Treatment-refractory, Chronic Neuropathic Pain

Quick Facts

Study Start:2022-11-01

Study Completion:2027-06-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05404581

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 80 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	1. Idiopathic pain syndromes will be excluded. Examples include: 1. Fibromyalgia syndrome 2. temporomandibular joint disorders 3. irritable bowel syndrome 4. chronic headaches 5. interstitial cystitis 6. chronic pelvic pain 7. whiplash-associated disorders 2. Subjects deemed poor candidates by a multidisciplinary team of pain clinicians including specialists in neurosurgery, pain management, and pain psychology: 1. Significant clinician concern(s) about reliability of subject-reported information, such as subject in active process of seeking disability for neuropathic pain 2. 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) 3. Recurrent substance-related legal problems (such as arrests for substance related disorderly conduct) 4. 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). 5. Suspected dementia based on neuropsychological screening or Mini Mental State Exam (MMSE) Score \< 25 3. Subjects with active psychiatric illness will be excluded. For the purpose of this study, active psychiatric illness includes: 1. History of significant psychiatric disorder (e.g., comorbid schizophrenia, bipolar disorder, suicidal ideation/attempts) that could interfere with interpretation of study endpoints. 2. Exhibiting current suicide ideation and/or a history of suicide attempt within past 2 years 3. been hospitalized for the treatment of a psychiatric illness within the past 2 years 4. received transcranial magnetic stimulation for depression treatment 5. received electroconvulsive therapy for depression 6. any presence or history of psychosis 4. Subjects with unstable cardiac status including: 1. Unstable angina pectoris on medication 2. Subjects with documented myocardial infarction within six months of protocol entry 3. Significant congestive heart failure defined with ejection fraction \< 40 4. Subjects with unstable ventricular arrhythmias 5. Subjects with atrial arrhythmias that are not rate-controlled 5. Severe hypertension (diastolic BP \> 100 on medication) 6. Subjects with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc. 7. On medications that increases the bleeding risk, based on the published guidelines41 which are currently recognized by the American Society of Regional Anesthesia and Pain Medicine, American Academy of Pain Medicine and the North American Neuromodulation Society; specifically: 1. Aspirin or another antiplatelet medication (clopidogrel, prasugrel, ticlopidine, abiciximab) for the last 7 days prior to treatment. 2. Oral, subcutaneous or intravenous anticoagulant medications, such as oral vitamin K inhibitors for the last 7 days, non-vitamin K inhibitor oral anticoagulant (dabigatran, apixaban, rivaroxaban) for the last 72 hours. 3. Intravenous or subcutaneous heparin-derived compounds for the last 48 hours. 8. Individuals who are not able or willing to tolerate prolonged hospitalization with continuous video EEG monitoring 9. Subjects participating or have participated in another clinical trial to investigate or treat chronic pain in the last 30 days 10. Subjects with risk factors for intraoperative or postoperative bleeding from a documented coagulopathy or if their serum coagulation studies (platelet count, PT, PTT, and INR) exceed the institutional laboratory limits. 11. Subjects with brain tumors or any significant intracranial mass. 12. Subjects with a history of seizure 13. Any illness that in the investigator's opinion preclude participation in this study 14. Pregnancy or lactation 15. Subjects with a true allergy to opioid medications which would preclude PET imaging 16. Legal incapacity or limited legal capacity 17. Subjects with a deep brain stimulation implant 18. History of hemorrhagic stroke or cerebrovascular event within the past year of treatment exhibiting incomplete resolution

Inclusion Criteria

Exclusion 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.

1. Idiopathic pain syndromes will be excluded. Examples include:
1. Fibromyalgia syndrome
2. temporomandibular joint disorders
3. irritable bowel syndrome
4. chronic headaches
5. interstitial cystitis
6. chronic pelvic pain
7. whiplash-associated disorders
2. Subjects deemed poor candidates by a multidisciplinary team of pain clinicians including specialists in neurosurgery, pain management, and pain psychology:
1. Significant clinician concern(s) about reliability of subject-reported information, such as subject in active process of seeking disability for neuropathic pain
2. 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)
3. Recurrent substance-related legal problems (such as arrests for substance related disorderly conduct)
4. 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).
5. Suspected dementia based on neuropsychological screening or Mini Mental State Exam (MMSE) Score \< 25
3. Subjects with active psychiatric illness will be excluded. For the purpose of this study, active psychiatric illness includes:
1. History of significant psychiatric disorder (e.g., comorbid schizophrenia, bipolar disorder, suicidal ideation/attempts) that could interfere with interpretation of study endpoints.
2. Exhibiting current suicide ideation and/or a history of suicide attempt within past 2 years
3. been hospitalized for the treatment of a psychiatric illness within the past 2 years
4. received transcranial magnetic stimulation for depression treatment
5. received electroconvulsive therapy for depression
6. any presence or history of psychosis
4. Subjects with unstable cardiac status including:
1. Unstable angina pectoris on medication
2. Subjects with documented myocardial infarction within six months of protocol entry
3. Significant congestive heart failure defined with ejection fraction \< 40
4. Subjects with unstable ventricular arrhythmias
5. Subjects with atrial arrhythmias that are not rate-controlled
5. Severe hypertension (diastolic BP \> 100 on medication)
6. Subjects with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc.
7. On medications that increases the bleeding risk, based on the published guidelines41 which are currently recognized by the American Society of Regional Anesthesia and Pain Medicine, American Academy of Pain Medicine and the North American Neuromodulation Society; specifically:
1. Aspirin or another antiplatelet medication (clopidogrel, prasugrel, ticlopidine, abiciximab) for the last 7 days prior to treatment.
2. Oral, subcutaneous or intravenous anticoagulant medications, such as oral vitamin K inhibitors for the last 7 days, non-vitamin K inhibitor oral anticoagulant (dabigatran, apixaban, rivaroxaban) for the last 72 hours.
3. Intravenous or subcutaneous heparin-derived compounds for the last 48 hours.
8. Individuals who are not able or willing to tolerate prolonged hospitalization with continuous video EEG monitoring
9. Subjects participating or have participated in another clinical trial to investigate or treat chronic pain in the last 30 days
10. Subjects with risk factors for intraoperative or postoperative bleeding from a documented coagulopathy or if their serum coagulation studies (platelet count, PT, PTT, and INR) exceed the institutional laboratory limits.
11. Subjects with brain tumors or any significant intracranial mass.
12. Subjects with a history of seizure
13. Any illness that in the investigator's opinion preclude participation in this study
14. Pregnancy or lactation
15. Subjects with a true allergy to opioid medications which would preclude PET imaging
16. Legal incapacity or limited legal capacity
17. Subjects with a deep brain stimulation implant
18. History of hemorrhagic stroke or cerebrovascular event within the past year of treatment exhibiting incomplete resolution

Contacts and Locations

Study Contact

Judy Beenhakker

CONTACT

434-982-1856

jgb3p@hscmail.mcc.virginia.edu

Zak Sturgill

CONTACT

434-243-9986

ffm7rc@virginia.edu

Principal Investigator

Jeff Elias, MD

PRINCIPAL_INVESTIGATOR

University of Virginia

Study Locations (Sites)

University of Virginia

Charlottesville, Virginia, 22903

United States

Collaborators and Investigators

Sponsor: University of Virginia

Jeff Elias, MD, PRINCIPAL_INVESTIGATOR, University of Virginia

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-11-01

Study Completion Date2027-06-30

Study Record Updates

Study Start Date2022-11-01

Study Completion Date2027-06-30

Terms related to this study

Keywords Provided by Researchers

stereoencephalography
deep brain stimulation
insula
neuromodulation

Additional Relevant MeSH Terms

Neuropathic Pain
Chronic Pain