A Pilot Study of Transcranial Magnetic Stimulation for Treatment of Methamphetamine Use Disorders
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Retention in the Study
研究概览
简要总结
This is a pilot study to test the feasibility of a recruitment strategy and study protocol to examine the effects of a dual target transcranial magnetic stimulation treatment in methamphetamine use disorder. The study will test intermittent theta burst stimulation (TBS) targeting the dorsolateral prefrontal cortex (DLPFC) combined with continuous TBS targeting the medial prefrontal cortex (MPFC) in people with methamphetamine use disorder (MAUD) who are engaged in psychosocial treatment. We will randomize the order in which these treatments are delivered at each treatment session, but all subjects will receive both treatments. Intermittent TBS targeting the DLPFC is approved by the Food and Drug Administration for major depressive disorder, and continuous TBS targeting the MPFC has been studied in cocaine use disorder. We will administer this dual target TBS daily for 2 weeks, followed by three times weekly for 2 weeks, and monitor depressive symptoms, anxiety, sleep, craving, quality of life, and methamphetamine use for three months. Changes in functional connectivity of brain circuits will be evaluated with functional magnetic resonance imaging (fMRI) before and after treatment. We expect to observe changes in connectivity between the DLPFC, MPFC, and other regions implicated in addiction and impulsivity. Furthermore, we will evaluate if baseline differences in functional connectivity can be used to predict response. Psychological tests focusing on state impulsivity and risk taking will be administered, and we expect to observe reductions in these characteristics after treatment. We will test this protocol in 20 patients recruited from clinical care settings at University of Iowa Hospitals and Clinics, University of New Mexico Health System, and University of Utah Health to illustrate the feasibility of recruitment and completing the protocol, to support an external funding proposal.
详细描述
Overview: This is a two-arm randomized controlled trial. Participants with MAUD will receive 16 sessions of dual-target theta burst stimulation to the DLPFC and MPFC over 4 weeks. Participants will be randomized to whether they receive stimulation to the DLPFC or MPFC first, but both sites will be stimulated at each treatment. We will follow outcomes for 12 weeks. Outcomes include treatment retention, craving, self-reported MA or stimulant use, urine drug screen results, depressive symptoms, anxiety symptoms, sleep quality, quality of life, response inhibition, and functional connectivity. Magnetic resonance imaging (MRI) to measure functional connectivity and a flanker task to measure response inhibition will be completed at baseline and four weeks. More detail is provided in the outcome measures section. Subjects will also complete the Big Five Inventory at baseline, a measure of personality characteristics, to explore how these relate to outcomes including retention in treatment and the study.
MR Image Acquisition: MRI will be completed at baseline and after the last TMS session. The MRI sessions will be conducted using research dedicated MRI scanners at each site. Anatomical images will include volumetric T1 and T2 weighted images with a 1.0 mm isotropic spatial resolution. Resting state fMRI will be performed to collect 20 minutes worth of data.
Statistical Analysis:
Retention in the Study and Psychosocial Treatment: We will describe the proportion of subjects who complete the 4-week TMS treatment period and complete each subsequent monthly follow-up visit, depending on randomization group. We will use Kaplan-Meier curves to describe retention in the study and in psychosocial treatment, and log-rank tests to compare them. If non-retention is common enough, we will use Cox regression to explore baseline measures as predictors of retention. We anticipate that multivariate analysis will not be feasible with the sample size.
Symptoms and Impulse Control Measures: Primary analyses for other measures will focus on changes over the 4-week TMS treatment period. Changes in symptoms evaluated weekly or biweekly (e.g. craving, depression, affect, anxiety, sleep) will be assessed using generalized linear mixed models with appropriate distributions. We anticipate a Poisson distribution for days of MA or other stimulant use and will use a binomial distribution with a logit link to evaluate changes in positive urine drug screens. Randomization group by time interactions will be the primary variables of interest to assess the differences between slopes of change between groups during treatment. Paired t-tests or Wilcoxon signed-rank tests will be used to evaluate changes in measures completed at baseline and after 4 weeks of treatment. We will compare measures at baseline and 4 weeks to those at 8 weeks and 12 weeks similarly, but in separate analyses since decay in effects may occur after TMS ends.
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
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with an active methamphetamine use disorder
- •Is engaged in psychosocial treatment or articulates a plan to engage in psychosocial treatment for methamphetamine use disorder during the study period
- •Age 18 to 60 years
- •Able to consent for treatment and research participation
- •English-speaking
- •Receiving care from UIHC's Addiction Medicine service. This includes patients in the Crisis Stabilization Unit, seen by the inpatient consultation service, enrolling in partial hospitalization or intensive outpatient treatment, or seen in the outpatient Addiction Medicine clinics.
排除标准
- •Age less than 18 years
- •Patients that are excluded during TMS assessment including: patients with epilepsy or seizure disorder, patients with implanted ferromagnetic equipment in their face or skull near the stimulation target.
- •Current medical treatment with clozapine or stimulants.
- •Current diagnosis of bipolar disorder, schizoaffective disorder, schizophrenia, that is deemed by research team psychiatrists not to have been drug-induced. Psychotic disorder not associated with drug use per the MINI International Neuropsychiatric Interview. Psychosis NOS, in remission, or drug-induced psychotic episodes are not exclusion criteria since these may be related to methamphetamine misuse.
- •Lacks the mental capacity to provide informed consent (i.e. not able to demonstrate understanding of the risks and benefits of participation)
- •Has a court appointed guardian.
- •Unstable medical illness.
- •Current diagnosis of neurological disorder or neurocognitive disorder.
- •Prior neurosurgical procedure.
- •History of seizure.
- •History of ECT treatment within the past three months.
- •History of any previous TMS treatment.
- •Known inability to complete the protocol, as assessed by asking them if they are able to make it to all visits for this study without assistance.
- •MRI Exclusion criteria:
- •Implanted device including pacemaker, coronary stent, defibrillator, or neurostimulation device that is not MRI-compatible
- •Metal in body including bullets, shrapnel, metal slivers
- •Claustrophobia
- •Uncontrolled high blood pressure
- •Atrial fibrillation
- •Significant heart disease
- •Hemodynamic instability
- •Kidney disease
研究组 & 干预措施
DPFC first
Participants in this arm will undergo all study procedures including consent; pre-, during, and post-psychological assessments; pre- and post- MRI and fMRI; 16 treatments of dual target TMS over a 4-week period; and substance use-related assessments to include substance use, withdrawal symptoms, and cravings to use. This arm will receive the dorsolateral prefrontal cortex stimulation first.
干预措施: Transcranial Magnetic Stimulation--DPFC first, MPFC second (Device)
MPFC first
Participants in this arm will undergo all study procedures including consent; pre-, during, and post-psychological assessments; pre- and post- MRI and fMRI; 16 treatments of dual target TMS over a 4-week period; and substance use-related assessments to include substance use, withdrawal symptoms, and cravings to use. This arm will receive the medial prefrontal cortex stimulation first.
干预措施: Transcranial Magnetic Stimulation--MPFC first, DPFC second (Device)
结局指标
主要结局
Retention in the Study
时间窗: Baseline to 12 weeks (continuous)
Time to study dropout (to assess feasibility and tolerability of the protocol)
Retention in Psychosocial Treatment
时间窗: Baseline to 18 days (continuous--assessed weekly)
Time to discontinuation of psychosocial treatment
次要结局
- Flanker Inhibitor Control and Attention Test, Age 12+(Baseline, 4 weeks)
- Functional Connectivity of the Dorsolateral Prefrontal Cortex and Anterior Insula(Baseline, 4 weeks)
- Functional Connectivity Dorsolateral Prefrontal Cortex and Anterior Cingulate Cortex(Baseline, 4 weeks)
- Functional Connectivity of the Medial Prefrontal Cortex and Ventral Striatum (Nucleus Accumbens)(Baseline, 4 weeks)
- Kirby Delay Discounting Questionnaire, 27 Item(Baseline, 4 weeks)
- Number of Days of Stimulant Use in the Past Week (Estimated Change Per Day)(Baseline, 1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, 12 weeks)
- Urine Drug Screen Positive for Stimulant(Baseline, 1 week, 2 weeks, 3 weeks, 4 weeks)
- Brief Substance Craving Scale (Estimated Change in Score Per Day)(12 weeks)
- Brief Addiction Monitor Use Subscale (Estimated Change in Score Per Day)(Baseline, 4 weeks, 8 weeks, 12 weeks)
- Brief Addiction Monitor Risk Factors Subscale (Estimated Change in Score Per Day)(Baseline, 4 weeks, 8 weeks, 12 weeks)
- Brief Addiction Monitor Protective Factors Subscale (Estimated Change in Score Per Day)(Baseline, 4 weeks, 8 weeks, 12 weeks)
- Brief Addiction Monitor Satisfaction With Progress Toward Achieving Recovery Goals (Estimated Change Per Day)(Baseline, 4 weeks, 8 weeks, 12 weeks)
- Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Estimated Change in Score Per Day)(Baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks)
- Patient Health Questionnaire--8 Item Scale (Estimated Change in Score Per Day)(Baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks)
- Generalized Anxiety Disorder 7-item Scale (Estimated Change Per Day)(Baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks)
- Assessment of Recovery Capital (Estimated Change Per Day)(Baseline, 4 weeks, 8 weeks, 12 weeks)
- Positive and Negative Affect Scale Positive Affect Score (Estimated Change Per Day)(Baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks)
- Positive and Negative Affect Scale Negative Affect Score (Estimated Change Per Day)(Baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks)
- Pittsburgh Sleep Quality Index (Estimated Change Per Day)(Baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks)
- Difficulties in Emotion Regulation Scale--Short Form (Estimated Change Per Day)(Baseline, 4 weeks)
- UPPS-P Impulsive Behavior Scale, 59-item Revised Version (Estimated Change Per Day)(Baseline, 4 weeks)
研究者
Ryan M. Carnahan
Professor
University of Iowa