Clinical trial NCT04085406: DBS of the SCC for the Treatment of Medically Refractory CLBP
Official title: Deep Brain Stimulation of the Subgenual Cingulate Cortex for the Treatment of Medically Refractory Chronic Low Back Pain
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Chronic Low-back Pain
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2019-09-11
Enrollment: 16
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change of at least 50% in pain scores on the visual analog scale (VAS) compared to baseline.
timeFrame: 12 months - the end of the crossover period
measure: Change in at least 50% in pain scores on the Pain Anxiety Symptoms Scale -- Short Form 20 (PASS SF-20) compared to baseline.
timeFrame: 12 months - the end of the crossover period
measure: At least 10% of study participants to experience one or more significant adverse events (SAEs)
timeFrame: 18 months - the end of the study
Secondary outcomes:
measure: Change in dose and/or frequency of opioid analgesic medication use in oral morphine equivalents.
timeFrame: 12 months - the end of the crossover period
measure: 50% improvement in McGill Pain Questionnaire (MPQ)
timeFrame: 12 months - the end of the crossover period
measure: Change in Short-Form 36 (SF-36) quality of life questionnaire score.
timeFrame: 12 months - the end of the crossover period
measure: Change in EuroQol 5-Domain (EQ-5D) Score
timeFrame: 12 months - the end of the crossover period
measure: Change in Montreal Cognitive Assessment Score (MoCA)
timeFrame: 12 months - the end of the crossover period
measure: Change in the Hamilton Depression Rating Scale (HAM-D)
timeFrame: 12 months - the end of the crossover period
measure: Change in the Oswestry Disability Index (ODI)
timeFrame: 12 months - the end of the crossover period
measure: Change in the NIH Toolbox Pain Interference Computer Adaptive Test (CAT)
timeFrame: 12 months - the end of the crossover period
measure: Change in the PROMIS Pain Intensity Scale 3a
timeFrame: 12 months - the end of the crossover period
measure: Change in the PROMIS Pain Behavior CAT
timeFrame: 12 months - the end of the crossover period
measure: Change in the NIH Toolbox Positive Affect CAT
timeFrame: 12 months - the end of the crossover period
measure: Change in the NIH Toolbox Sadness CAT
timeFrame: 12 months - the end of the crossover period
measure: Change in the NIH Toolbox General Life Satisfaction CAT
timeFrame: 12 months - the end of the crossover period
measure: Change in the NIH Toolbox Perceived Stress Fixed Form (FF)
timeFrame: 12 months - the end of the crossover period
measure: Change in the PROMIS Prescription Pain Medication Misuse CAT
timeFrame: 12 months - the end of the crossover period
measure: Change in the NIH Toolbox Locomotion
timeFrame: 12 months - the end of the crossover period
measure: Change in the NIH Pain Intensity Survey
timeFrame: 12 months - the end of the crossover period
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: UCLA Department of Neurosurgery
name: Ausaf Bari, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: