DBS of the SCC for the Treatment of Medically Refractory CLBP

Официальное название

Deep Brain Stimulation of the Subgenual Cingulate Cortex for the Treatment of Medically Refractory Chronic Low Back Pain

Обзор

The purpose of this study is to evaluate the feasibility and preliminary efficacy of deep brain stimulation of the subgenual cingulate cortex for the treatment of chronic medically-refractory low back pain using a randomized double-blind crossover design.

Подробное описание

Chronic low back pain (CLBP) is one of the most ubiquitous and intractable problems in medicine and a significant source of patient suffering and disability, leading to opioid misuse and addiction. Previous neuromodulatory therapies for CLBP have focused primarily on spinal etiologies and intra-spinal mechanisms of pain transmission. However, existing pharmacological and neuromodulatory therapies have not been successful in treating CLBP. This project aims to address critical gaps and the unmet therapeutic needs of CLBP patients by using the Abbott Infinity DBS System; a next generation DBS device with directional steering capability implanted bilaterally in the subgenual cingulate cortex (SCC) to engage networks known to mediate the affective component of CLBP. The objective is to (1) Assess the preliminary efficacy of DBS of the SCC in the treatment of medically refractory CLBP; (2) Demonstrate the safety and feasibility of SCC DBS for CLBP; and (3) Develop diffusion tensor imaging (DTI)-based blueprints of response to SCC DBS for CLBP. The overall impact of this proof-of-concept pilot trial includes validation of the concept that suffering from CLBP results from pathological activity in affective brain networks, that these networks can be accurately engaged using a next-generation directional DBS device in a safe and feasible manner, and the discover of neuroimaging biomarkers of response to SCC DBS for CLBP.

Вмешательства

• Устройство Deep Brain Stimulation of the Subgenus Cingulate Cortex
  The Abbott Infinity DBS device will be surgically implanted in the bilateral subgenual cingulate cortex to provide electrical stimulation to this region.

Первичные конечные точки

• Change of at least 50% in pain scores on the visual analog scale (VAS) compared to baseline. [Срок оценки: 12 months - the end of the crossover period]
• Change in at least 50% in pain scores on the Pain Anxiety Symptoms Scale -- Short Form 20 (PASS SF-20) compared to baseline. [Срок оценки: 12 months - the end of the crossover period]
• At least 10% of study participants to experience one or more significant adverse events (SAEs) [Срок оценки: 18 months - the end of the study]

Вторичные конечные точки (12)

• Change in dose and/or frequency of opioid analgesic medication use in oral morphine equivalents. [Срок оценки: 12 months - the end of the crossover period]
• 50% improvement in McGill Pain Questionnaire (MPQ) [Срок оценки: 12 months - the end of the crossover period]
• Change in Short-Form 36 (SF-36) quality of life questionnaire score. [Срок оценки: 12 months - the end of the crossover period]
• Change in EuroQol 5-Domain (EQ-5D) Score [Срок оценки: 12 months - the end of the crossover period]
• Change in Montreal Cognitive Assessment Score (MoCA) [Срок оценки: 12 months - the end of the crossover period]
• Change in the Hamilton Depression Rating Scale (HAM-D) [Срок оценки: 12 months - the end of the crossover period]
• Change in the Oswestry Disability Index (ODI) [Срок оценки: 12 months - the end of the crossover period]
• Change in the NIH Toolbox Pain Interference Computer Adaptive Test (CAT) [Срок оценки: 12 months - the end of the crossover period]
• Change in the PROMIS Pain Intensity Scale 3a [Срок оценки: 12 months - the end of the crossover period]
• Change in the PROMIS Pain Behavior CAT [Срок оценки: 12 months - the end of the crossover period]
• Change in the NIH Toolbox Positive Affect CAT [Срок оценки: 12 months - the end of the crossover period]
• Change in the NIH Toolbox Sadness CAT [Срок оценки: 12 months - the end of the crossover period]

Критерии участия

Критерии включения

• Pain secondary to failed back surgery syndrome (FBSS) as defined by persistent low back pain despite prior surgical interventions.
• Self-reported average back pain intensity of greater than 8 out of 10 on the Visual Analog Scale (VAS) documented over greater than 2 years.
• Failure to achieve at least 50% pain relief from a trial of spinal cord stimulation (SCS) or less than 50% pain relief after 3 months of SCS therapy or patient refuses/rejects SCS trial
• Failure to achieve at least 50% pain relief in response to at least 4 weeks of physical therapy.
• Failure to achieve at least 50% pain relief in response to at least 2 percutaneous spinal pain procedures.
• Failure to achieve at least 50% pain relief in response to 3 months of opioid therapy (at least 20 MEQ/day) or inability to increase or tolerate opioid therapy due to dose-limiting side effects).
• Failure to achieve at least 50% pain relief in response to a 3-month trial of at least one other class of pain medication in addition to opioid therapy or inability to tolerate increasing doses of non-opioid pain medications due to dose-limiting side effects.
• Lack of a surgically correctible etiology for the pain as determined by 2 independent neurosurgeons
• Age greater than 40 years of age.
• Ability to give informed consent in accordance with institutional policies and participate in the 1.5-year follow-up, involving assessments and stimulator adjustments.
• Willingness to share unexpected neurological or psychiatric symptoms with study clinicians.

Критерии исключения

• Significant neurocognitive impairment (MoCA < 26).
• Age > 75 years.
• History of implant-related infection.
• History of bleeding disorder or immune-compromise.
• Psychiatric comorbidity other than depression or generalized anxiety disorder, as determined by MINI International Neuropsychiatric Interview.
• Patients with neurological diagnoses that may reduce the response to or increase the risk of DBS including neurodegenerative conditions, severe movement disorders, demyelinating disorders, syringomyelia, epilepsy or history of seizures, history of CNS tumors (spinal and/or cranial), history of serious head injury with loss of consciousness, history of stroke, surgically reversible peripheral pain syndromes including surgically correctable radiculopathy, and severe peripheral neuropathy.
• Patients who have undergone spine surgery within the previous 3 months.
• Major medical co-morbidities increasing the risk of surgery including uncontrolled hypertension, severe diabetes, major organ system failure, history of hemorrhagic stroke, need for chronic anticoagulation, active infection, immunocompromised state or malignancy with < 5 years life expectancy.
• Individuals with a currently implanted SCS device.
• Individuals with a life expectancy less than 1 year due to any cause.
• Individuals involved in an injury claim under current litigation.
• Individuals with a pending or approved worker's compensation claim.
• Patient living greater than 100 miles from UCLA.
• Suicide attempt in the last two years and/or presence of a suicide plan (an answer of Yes to Question C4 in Section C- Suicidality of MINI International Neuropsychiatric Interview).
• Alcohol or illicit substance use disorder (other than nicotine) within the last 6 months, unstable remission of substance abuse, or chart evidence that co-morbid substance use disorder could account for lack of treatment response.
• Uncontrolled medical condition including cardiovascular problems and diabetes.
• Pregnant or planning to become pregnant.
• Use of warfarin or other blood thinners.
• Significant structural abnormality on preoperative brain MRI.
• Contraindications to MRIs or the need for recurrent body MRIs.
• Presence of cardiac pacemakers/defibrillators, implanted medication pumps, intra-cardiac lines, any intracranial implants (e.g., aneurysm clip, shunt, cochlear implant, electrodes) or other implanted stimulators.
• History of prior cranial neurosurgery.
• Patients unable to discontinue any existing therapeutic diathermy.
• Individuals who are concomitantly participating in another clinical study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 2 центра

• University of California Los Angeles — Los Angeles
• University of Texas Southwestern Medical Center — Dallas

Идентификаторы

NCT: NCT04085406 · UH3NS113661 · UH3NS113661

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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