Vanderbilt Integrated Community TMS for Opioid Recovery
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Determining the effects of active left-DLPFC targeted iTBS compared to sham on craving and opioid use in 100 people with OUD through the Opioid Craving Scale.
研究概览
简要总结
The main purpose of this study is to learn how stimulating a region in the brain influences craving and opioid use. The brain will be stimulated using TMS. Participants may choose to receive brain imaging (magnetic resonance imaging, MRI) as part of this study. The MRI will be used to identify areas in the brain that to stimulate and to measure brain changes as a result of TMS.
Participants will be asked to attend a total of 12 visits over about 5 months. Each visit will last between 1-2 hours with breaks. The study will involve interviews, questionnaires, computer tasks, TMS, and optional MRIs.
There are minor risks associated with this study. Answering some of the study questionnaires may cause stress or fatigue. The physical risks of TMS are low. Participants may experience mild pain or headache during or after receiving TMS. These symptoms may extend to adjacent areas of the face. The discomfort may be associated with twitching or movement of these areas during stimulation. This is generally transient and can be treated with over-the-counter pain medication. To minimize any risk of hearing loss during TMS, participants wear earplugs for the entire procedure. An evaluation of the participant's medical history will also be completed to ensure that it will be safe for participants to receive TMS. There is no direct benefit to participants from being in this study. However, participation may help others in the future as a result of knowledge gained from the research. The physical risks of the optional MRI are minimal, and a health questionnaire will be filled out before to determine if it is safe for participants to complete the MRI.
Confidentiality:
All efforts, within reason, will be made to keep personal information in participants' research records confidential but total confidentiality cannot be guaranteed. Documents containing identifiable subject information, like this consent form, will be stored in locked filing cabinets located in the Departments of Psychiatry and Radiology at Vanderbilt. Electronic files containing identifiable information will be stored on password protected systems at Vanderbilt. If a Week 10, 12, or 20 study visit is conducted over video-conferencing, links to the video-call will be sent only to the research participant and approved staff. Video-calls will take place in private locations where the risk of someone hearing or seeing the research visit is minimized. Subjects will be assigned a numeric code that will be used to label all research data, including brain imaging scans. Only Dr. Ward and approved research staff will have access to this data. Only de-identified data will be stored on this server.
Disclosures that participants consent to in this document are not protected. This includes putting research data in the medical record or sharing research data for this study or future research. Disclosures that participants make are also not protected.
Privacy:
Any samples and information about participants may be made available to others to use for research. To protect privacy, participant's name's will not be released. Participants will not receive any benefit as a result of the tests done on samples. These tests may help us or other researchers learn more about the causes, risks, treatments, or how to prevent this and other health problems.
Study Results:
Participant's individual study results will not be shared with them. The final results of the study will potentially be published in the scientific literature.
详细描述
Opioid Use Disorder is a Public Health Crisis with a High Risk of Relapse Worldwide, opioid use disorder (OUD) affects >16 million people annually, and >300 people/day die from overdose. Buprenorphine is an effective medication for OUD that reduces use, relapse, and mortality. However, within 6 months of starting buprenorphine, only 50% continue treatment and 91% will relapse. The 3-month period following buprenorphine initiation is highest risk for treatment discontinuation and relapse. Those who discontinue treatment have high risk of relapse and overdose. Thus, personalized interventions in the period following buprenorphine initiation may improve retention and reduce relapse. The strongest predictor of relapse is craving, defined as a "strong desire for drugs,". Following buprenorphine initiation, craving remains the top predictor of relapse. Relapse occurs when the urge to use (i.e., craving) is outweighed by the ability to resist that urge (i.e. inhibitory control). Higher inhibitory control is associated with less craving and less relapse. After an acute period of abstinence, individuals with OUD continue to struggle with craving, poor inhibitory control, depression, pain, and sleep disturbance, even with buprenorphine treatment. Both patients (The Voice of the Patient: A Series of Reports From the US Food and Drug Administration's (FDA's) Patient-Focused Drug Development Initiative: Opioid Use Disorder 2018) and experts have called for novel, symptom-specific interventions that enable personalized treatment of these refractory symptoms of OUD. Craving and inhibitory control can be readily measured and quantified using broadly available behavioral tasks (e.g., cue reactivity, go/no-go) and are targets for intervention.
Substance Use Disorder Symptoms are Linked to Brain Circuit Dysfunction The brain correlates of craving and inhibitory control are well-established in frontal-striatal circuitry, and it is well-known that individuals with substance use disorders have dysfunction in these circuits. Craving and impaired inhibitory control have been linked to decreased functional connectivity between the dorsolateral prefrontal cortex (DLPFC) and dorsal striatum. Therefore, modulating connectivity in this circuit may serve as effective interventions to treat substance use disorders.
iTBS is an FDA-Approved Treatment for Depression with Promising Applications for OUD. Repetitive transcranial magnetic stimulation (rTMS) is a form of non-invasive brain stimulation that uses electromagnetic fields to temporarily change neuronal patterns of connectivity in brain networks. When international safety guidelines are followed, rTMS is a safe and well-tolerated intervention in individuals with and without psychiatric illness. rTMS is also a versatile research tool whose stimulation parameters can be changed. Depending on the parameters, rTMS can increase or decrease brain activity. Specifically, intermittent theta burst stimulation (iTBS) tends to increase brain activity, while continuous theta burst stimulation (cTBS) tends to decrease brain activity.
rTMS is FDA-approved for the treatment of major depressive disorder, obsessive-compulsive disorder, and smoking cessation. rTMS has also shown promising results in research studies as a potential treatment for substance use disorders. Multiple systematic reviews have observed that rTMS reduces substance use and craving across substance use disorders, including OUD.
In studies of rTMS for OUD, the majority of trials have applied high frequency (10-20 Hz) rTMS or iTBS to the L DLPFC and observed significant reductions in craving and opioid use. It is hypothesized that applying high frequency (10-20 Hz) rTMS or iTBS to the L DLPFC will increase DLPFC activation and increase connectivity between the DLPFC and dorsal striatum, thereby improving inhibitory control and reducing craving and opioid use. In preliminary data for this proposal, a single session of iTBS applied to the L DLPFC in individuals with OUD receiving medication for OUD significantly reduced craving (n=30, p<.03).
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
- Single (Participant)
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
- •Age between 18-65 years
- •Diagnosis of OUD according to DSM-5 criteria and confirmed by SCID (First et al. 2015)
- •Meets either of the following criteria: (1) reports opioid craving of 2 or greater on a 0-10 scale, or (2) has returned to opioid use at least once within the past 12 months.
- •Currently Prescribed Buprenorphine for the treatment of opioid use disorder
- •Must be able to read, speak and understand English
- •Must be judged by study staff to be capable of completing the study procedures
- •Participants will be in stable outpatient psychiatric treatment and psychiatrically stable.
排除标准
- •DSM-5 intellectual disability
- •Substance use disorder (other than opioid, nicotine, or cannabis) within the past three months
- •Current, active suicidal ideation with intent or plan
- •Positive urine drug screen for illicit substance use that can increase seizure risk (cocaine, benzodiazepines, amphetamine, methamphetamine)
- •History of psychosis in the past 3 months or diagnosis of a primary psychotic disorder
- •Any history of a progressive or genetic neurologic disorder (e.g. Parkinson's disease, multiple sclerosis, tuberous sclerosis, Alzheimer's Disease) or acquired neurological disease (e.g. stroke, traumatic brain injury, tumor), including intracranial lesions
- •History of head trauma resulting in any loss of consciousness (>15 minutes) or neurological sequelae
- •Current history of poorly controlled headaches including chronic medication for migraine prevention
- •History of fainting spells of unknown or undetermined etiology that might constitute seizures
- •History of seizures, diagnosis of epilepsy, or immediate (1st degree relative) family history epilepsy with the exception of a single seizure of benign etiology (e.g. febrile seizures) in the judgment of a board-certified neurologist
- •Chronic (particularly) uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.)
- •Any metal in the brain or skull (excluding dental fillings) or elsewhere in the body unless cleared by the responsible covering MD (e.g. MRI compatible joint replacement)
- •Any devices such as pacemaker, medication pump, nerve stimulator, TENS unit, ventriculo-peritoneal shunt unless cleared by the responsible covering MD
- •All female participants of child-bearing age will be required to have a pregnancy test; any participant who is pregnant or planning to become pregnant will not be enrolled in the study
- •Medications will be reviewed by the responsible covering physician and a decision about inclusion will be made based on the participant's past medical history, drug dose, history of recent medication changes or duration of treatment, and use of CNS active drugs. The published TMS guidelines review of medications to be considered with rTMS will be taken into consideration given their described effects on cortical excitability measures.
- •Participants who, in the investigator's opinion, might not be suitable for the study or would be unable to tolerate the study visit
研究组 & 干预措施
L DLPFC-Targeted iTBS
8 weekly sessions of L DLPFC-targeted iTBS.
干预措施: Device: Repetitive Transcranial Magnetic Stimulation (rTMS) (Device)
L DLPFC-Targeted Sham TMS
8 weekly sessions of L DLPFC-targeted sham TMS.
干预措施: Device: Repetitive Transcranial Magnetic Stimulation (rTMS) (Device)
结局指标
主要结局
Determining the effects of active left-DLPFC targeted iTBS compared to sham on craving and opioid use in 100 people with OUD through the Opioid Craving Scale.
时间窗: From the start of the study (screening visit) to the 20 week follow-up visit.
The primary outcome is to determine the effects of active left-DLPFC targeted iTBS compared to sham on craving in 100 people with OUD. Specifically, this study seeks to provide evidence that L DLFPC-targeted iTBS leads to reduced craving use in individuals with OUD. Participants' craving and drug use will be assessed prior to receiving iTBS, during iTBS intervention and following the end of iTBS (10, 12 and 20 weeks). Craving will be measured using the Visual Analogue Scale (VAS) on the Opioid Craving Scale (OCS).
Assessing Changes in Opioid Craving Following L DLPFC-Targeted iTBS Administration through the Visual Analog Scale, Self-Reports, and changes in cue reactivity, as measured during an MRI.
时间窗: From the start of the study (screening visit) to the 20 week follow-up visit.
Aim 1: Determine the effects of an FDA-approved protocol (active L DLPFC-targeted iTBS compared to sham) on craving and opioid use in people with OUD (n=100). Hypothesis: Active DLFPC-targeted iTBS will reduce craving and opioid use in people with OUD. This will be assessed by analyzing responses on a Visual Analog Scale where participants rate their craving for opioids on a scale of 1-10 during each visit. Craving will also be assessed using the cue reactivity task in an MRI to observe changes in brain connectivity during a cue-reactivity task where participants view images of opiods while periodically ranking their craving.
次要结局
- Determining if left DLPFC functional connectivity change is associated with change in craving on the OCS (n=50) through resting state MRI imaging.(From the start of the study (screening visit) to the 20 week follow-up visit.)
研究者
Heather Burrell Ward
Principle Investigator
Vanderbilt University Medical Center