Understanding the Mechanistic, Neurophysiological, and Antinociceptive Effects of Transcutaneous Auricular Neurostimulation for Treatment of Chronic Pain
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Clinical opioid withdrawal scale (COWS)
研究概览
简要总结
The purpose of the study is to find out how a stimulation device worn on the ear works. This device is thought to stimulate nerves in the area around the ear to change the signals in the brain. The device has been shown to reduce pain and to reduce the symptoms of withdrawal. The investigator will also investigate changes in the way each participant perceive sensations of pressure and heat. The participant will be asked to reduce the amount of pain medication that they take. Then, the participant will spend several days and nights in the Clinical Research Center at UTMB (University of Texas Medical Branch) in Galveston. During that time, the participant will be monitored for withdrawal symptoms and will receive either active (e.g., "real") brain stimulation or sham (e.g., "fake") brain stimulation for two days (four hours each day). At two times over the course of the study (before and after ear stimulation treatment), the participant will complete questionnaires about their pain score and how they are feeling, sensory testing, and will undergo magnetic resonance imaging (MRI) of their brain. The investigator will collect the following information from the participant's medical record: age, gender, medication history, medical diagnoses, recent vital signs, past doctor visits or hospital stays, and results of urine drug tests. Participation in this study will last approximately four days, and the participant will stay in the Clinical Research Center.
详细描述
Rationale and Aims
The current project will build on the previous tAN (transcutaneous auricular neurostimulation) research and clinical studies on chronic pain and opioid withdrawal, ultimately providing a "neural blueprint" of how tAN therapy can mitigate pain and opioid withdrawal symptoms. The investigators will conduct a clinical mechanistic trial of tAN in chronic pain patients tapering from therapeutic opioids. The study will accomplish the following Aim and address the following hypotheses:
Aim: Establish the functional MRI (fMRI) neurophysiological signature specifically underlying tAN-based analgesia in chronic pain participants undergoing an opioid taper.
Hypothesis 1: Chronic pain participants who receive tAN stimulation will demonstrate increased fMRI signal activation in vagal afferents within the brainstem compared to sham treatment.
Hypothesis 2: Chronic pain participants who receive tAN will demonstrate decreased fMRI signal activation in the cortical and subcortical pain network compared to sham treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The placement of either active or sham tAN device will be done by dedicated and unblinded study personnel. These study personnel will administer active tAN or sham tAN stimulation and have no additional involvement with participants or data collection. No other study staff members at UTMB who interact with participants or collect data will know which type of stimulation the participants received. Participants will additionally remain unaware (e.g., masked) of which type of tAN they are receiving until after study completion.
Active or sham auricular stimulation will be conducted using the FDA-cleared tAN device (Sparrow®) manufactured by Spark Biomedical (Dallas, TX). The tAN devices are portable, wearable systems with two channels of stimulation (auricular vagus and auricular trigeminal).
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females between 18 and 65 years of age
- •Participant is able to provide informed consent and function at an intellectual level sufficient for study requirements
- •Presence of pain on more than half of the days in the last six months
- •Must have proof of prescribed medication by either showing a prescription bottle with the individual's name or the presence of a prescription on the Prescription Drug Monitoring Program (PDMP)
- •Willingness to taper opioid dose by at least 10%
- •Patient or provider requests opioid dose reduction or discontinuation.
- •Urine Drug Screen (UDS) must be positive for their prescribed opioid
- •Urine Drug Test must be negative for illicit drugs, benzodiazepines, and nonprescribed opioids
- •Must agree to use nicotine patches and/or gum instead of smoking or vaping in the UTMB facilities
排除标准
- •Currently receiving treatment for cancer
- •Participant has a history of epileptic seizures
- •Participant has a history of neurological diseases or traumatic brain injury
- •Participant has abnormal ear anatomy or current ear infection present
- •Participant has presence of devices, e.g., pacemakers, cochlear prosthesis, neurostimulators
- •Currently receiving a prescription benzodiazepine medication
- •Current prescription opioid dose >50 MME/day
- •Current abuse of illicit drugs or alcohol (nicotine use is acceptable).
- •Surgery within the previous month
- •Report of suicide attempt or psychiatric hospitalization in the past 10 years.
- •Current suicidal ideation with specific plan or intent
- •Women of childbearing potential not using adequate contraception as per investigator judgment or not willing to comply with contraception for the duration of the study
- •Females who are pregnant or lactating
- •Participant has any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial
研究组 & 干预措施
tAN stimulation - active
Active or sham auricular stimulation will be conducted using the FDA-cleared tAN device (Sparrow®) manufactured by Spark Biomedical (Dallas, TX). The tAN devices are portable, wearable systems with two channels of stimulation (auricular vagus and auricular trigeminal). Two individual stimulation frequencies will be set: 15 Hz at cymba concha (Region1/Channel 1; vagal innervation) and 100 Hz adjacently anterior to the tragus (Region 2/Channel 2; trigeminal innervation). The pulse duration will be set at 250 µs for all participants. The stimulation intensities (mA) will be set at 1.0 and 1.4 (for Regions 1 and 2, respectively) based on values observed in previous clinical studies. If the participant states that the stimulation intensity is discomforting or unperceivable, the study personnel will gradually decrease/increase the intensity until a comfortable stimulation intensity is achieved
干预措施: transcutaneous Auricular neurostimulation - Active (Device)
tAN stimulation - sham
Active or sham auricular stimulation will be conducted using the FDA-cleared tAN device (Sparrow®) manufactured by Spark Biomedical (Dallas, TX). The tAN devices are portable, wearable systems with two channels of stimulation (auricular vagus and auricular trigeminal). Two individual stimulation frequencies will be set: 15 Hz at cymba concha (Region1/Channel 1; vagal innervation) and 100 Hz adjacently anterior to the tragus (Region 2/Channel 2; trigeminal innervation). The pulse duration will be set at 250 µs for all participants. The stimulation intensities (mA) will be set at 1.0 and 1.4 (for Regions 1 and 2, respectively) based on values observed in previous clinical studies. If the participant states that the stimulation intensity is discomforting or unperceivable, the study personnel will gradually decrease/increase the intensity until a comfortable stimulation intensity is achieved.
干预措施: transcutaneous auricular neurostimulation - Sham (Device)
结局指标
主要结局
Clinical opioid withdrawal scale (COWS)
时间窗: day 1 and day 4
Examination and scoring of symptoms of opioid withdrawal. score range is 1-36 with 1-2 mild, 3-24 moderate, and 25-36 severe withdrawal symptoms measured pre-treatment (day 1) and post-treatment (day4
次要结局
- Pain, enjoyment, and general activity (PEG3)(day 1 and day 4)
- Patient Health Questionnaire (PHQ9)(day 1 and day 4)
- Patient reported outcome measurement anxiety (PROMIS-A): questionnaire(day 1 and day4)
- Patient reported outcome measurement depression (PROMIS-D): questionnaire(day 1 and day4)
研究者
Wilkes, Denise
Professor
The University of Texas Medical Branch, Galveston