Relapse Prevention in Stimulant Use Disorder
试验速览
- 阶段
- 早期 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Stimulant use 1 month after leaving inpatient treatment (self-report)
研究概览
简要总结
The purpose of this study is to assess the relationship between bupropion, stimulant use and relapse, ADHD (Attention Deficit Hyperactivity Disorder), and measures of mood, drug craving, and inhibitory control in individuals enrolled in inpatient treatment for stimulant-use disorder with and without ADHD.
The experimenters hypothesize that Bupropion and Contrave (Bupropion/Naltrexone) will increase inhibitory control and decrease drug craving and depressive symptoms in recently abstinent stimulant users in inpatient treatment with effects greater than those seen in recently abstinent stimulant users completing inpatient treatment as usual. An additional hypothesis is that relapse rates after leaving inpatient treatment in the group receiving bupropion will be lower than those of the group completing inpatient treatment as usual.
The study design consists of four assessments of drug craving, inhibitory control, impulsive choice, and mood (depression and anxiety). The timepoints for these assessments include: A. baseline after entering treatment B. 2 weeks after starting drug C. 8 weeks after starting drug, and D. 1 month after leaving treatment. Following eligibility screening, 60 stimulant users will be enrolled in one of 3 groups. Group 1 Bupropion Active Group: 20 subjects will receive bupropion for 8 weeks during inpatient treatment. Group 2 Contrave Active Group: 20 subjects will receive Contrave for 8 weeks during inpatient treatment. Group 3 Control Group: 20 subjects enrolled in inpatient treatment will complete treatment as usual as well as the four assessments (A-D) described above but will not receive drug (convenience control). Half of the subjects in each group will be diagnosed with ADHD and half will not, for a total of 10 subjects per group with ADHD.
详细描述
- Participants will be recruited from the Clare Foundation (CLARE|MATRIX), where they will be residing in a residential substance use disorder program. Potential participants recently admitted with stimulant use disorder will be given a flyer/research information sheet describing the study when they are admitted to the study. Interested parties will sign their name on the sheet to indicate their interest, and will meet with a UCLA research associate at Clare to discuss details of the protocol and undergo initial screening following verbal consent. Initial screening involves a one page screening sheet and discussing the information sheet with the research associate at Clare.
- If participants remain eligible following initial screening, they will enroll in the study and the UCLA research associate will set up an in person screening to sign the informed consent form and undergo additional screening. After completing informed consent and going through the informed consent quiz, a Nurse Practitioner or physician will take a medical history, take a personal and family health profile, perform a physical examination (History & Physical). Participants who provide written consent will complete questionnaires about their mood, medical, psychiatric and drug use history, personality and life experiences. The screening visit will also include a psychiatric diagnostic interview (MINI International Neuropsychiatric Interview M.I.N.I) completed by a trained diagnostician. Participants will also give a urine sample to determine what drugs they have recently used, a breath sample to determine the carbon monoxide levels in their system. Participants will travel to UCLA to give a blood sample to assess complete blood count, metabolic panel, screening for infectious diseases (Hepatitis B and C, HIV, syphilis) and tests of kidney function and receive an ECG (electrocardiogram). After all screening procedures have been completed, a study physician will collect and review ECG and laboratory tests to determine eligibility.
- After completing all screening procedures, eligible participants will complete the following baseline assessments:
A) Visit 1:
i. Prior to completing cognitive tasks behavioral testing, participants will will have their blood drawn by a London laboratory phlebotomist or will visit the Clinical and Translational Research Center (CTRC), where a registered nurse will draw approximately 40mL of blood. Blood samples will be assayed for genetic markers associated with smoking and stimulant use. The purpose of the genetic analysis is to examine the relationship between genetic polymorphisms, treatment outcomes, circulating study drug, and measures of cognitive function.
The DNA (deoxyribonucleic acid) samples acquired from this protocol will be added to a larger database of DNA samples collected from participants in London Laboratory protocols. DNA samples will be stored for future use other than the aims and goals of this study. Participants will not receive their results because our laboratory is only qualified for genetic analyses associated with research purposes and is not certified for clinical assessment of genetic information.
This blood sample will also be used to determine follicular and luteal phase in female participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
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
- •English fluency (in order to provide informed consent and complete questionnaires)
- •Age of 18-65 years inclusive
- •Meeting DSM 5 criteria for Stimulant-use disorder
- •Being 2-8 weeks abstinent from drugs of abuse other than nicotine (in cigarettes)
- •Vital signs as follows: resting pulse between 50 and 95 bpm, blood pressures between 90-150 mm Hg systolic and 45-95 mm Hg diastolic (inclusive)
- •Hematology and chemistry laboratory test results within normal (+/- 20%) limits and/or indicative of normal kidney function (estimated glomerular filtration rate ≥ 90 ml/min/1.73 m2) and/or not indicative of active disorder or infection.
- •Baseline ECG demonstrating normal conduction (including QTc) without clinically significant arrhythmias
- •Absence of clinically significant contraindications for participation, in the judgment of the admitting physician and the principal investigator, assessed by a medical history and physical examination.
- •Entering into and remaining in treatment voluntarily.
排除标准
- •Age of <18 or >65 years.
- •Current or past history of seizure disorder, including alcohol- or stimulant-related seizure, or significant family history of idiopathic seizure disorder or conditions that increase seizure risk (arteriovenous malformation, severe head injury, CNS tumor, CNS infection, stroke, anorexia nervosa or bulimia (current or prior diagnosis), and current use of drugs that lower seizure threshold
- •Current severe substance use disorder assessed by the MINI on any psychoactive substance (e.g., opioids) other than methamphetamine, cocaine or nicotine, or have physiological dependence on alcohol or a sedative-hypnotic (e.g., a benzodiazepine) requiring medical detoxification, or undergoing abrupt discontinuation of ethanol or sedatives including anticonvulsants, barbiturates, or benzodiazepines
- •Prior therapy with any opiate-substitutes (methadone, LAAM, buprenorphine) within 2 months of enrollment.
- •Previous adverse reaction to Bupropion or Naltrexone.
- •Current use of a. Bupropion, Naltrexone, opiates or opiate-substitutes, stimulants b.Any medications that directly affect dopaminergic or serotonergic neurotransmission in brain (i.e., SNRI, MAO-I, TCA) c. Any neuroleptic agent d. Systemic corticosteroids, Xanthines (i.e., theophylline) e. Sympathomimetics f. Antiretrovirals (i.e., nelfinavir, ritonavir and efavirenz) g. Linezolid or IV methylene blue h. Warfarin
- •MAO-I use in the 2 weeks before enrollment
- •Disease or injury preventing use of both eyes and ability to complete computer tasks assessing cognitive function (e.g. glaucoma, colorblindness)
- •Brain injury with loss of consciousness >30 min
- •Pre-existing psychotic disorders, bipolar disorder, organic brain disorder, or dementia as assessed by the MINI interview, or medical disorder, any of which require an excluded medication (e.g., antidepressant, neuroleptic, systemic corticosteroid, xanthine) or which would make medication compliance difficult.
- •Electroconvulsive therapy within the 90 days before screening.
- •Current suicidal ideation or plan, as assessed by the MINI
- •Untreated or unstable medical illness including, but not limited to endocrine, autoimmune, renal, hepatic, active infectious disease (like active tuberculosis and active syphilis), diabetes or use of insulin, neurological disorders (including, but not limited to Parkinson's disease, dementia.), uncontrolled hypertension (See NIDA Guidelines on Hypertension in the Operations Manual), significant heart disease (including but not limited to angina, any ECG/cardiovascular abnormality e.g., QTc interval prolongation > 450 milliseconds in men or 480 milliseconds in women or myocardial infarction within one year of enrollment).
- •Pregnancy or lactation [Note: Female participants must be either postmenopausal or using a reliable form of contraception (e.g., abstinence, oral contraceptive pills, intrauterine device, sterilization, condoms or spermicide). Women must have negative urine tests for pregnancy at study entry and at every weekly session]
- •Diagnosis of adult (i.e., 21 years or older) asthma, or chronic obstructive pulmonary disease (COPD), including those with a history of acute asthma within the 2 years before enrollment, and current or recent (past 3 months) treatment with theophylline, or have an FEV1 <70 %.
- •Currently receiving HIV treatment with antiviral and/or non-antiviral therapy since these drugs may increase the bupropion levels. The following list of HIV treatment/medications may be used: Norvir, Reyataz, Truvada, Videx, Viread, Androgel and Trizovir. Note: Any HIV medication not on this list should be approved by the medical monitor.
- •Neurological disorder that would compromise informed consent or complicate data interpretation (e.g., organic brain disease or dementia).
- •Any condition that, as deemed by the investigators and study physician, would compromise safe participation.
- •Meeting the definition of "prisoner" status, as defined by 45 CFR 46.303(c). This will be determined by UCLA research associates in collaboration with counselors at the Clare Matrix to confirm legal issues. Initial eligibility will be determined upon entry into the treatment center based on information given by the subject when entering treatment and the criteria added to the screening sheet.
研究组 & 干预措施
Contrave
Participants will receive daily weight loss medication, Contrave, at a dose of 360 mg (Naltrexone HCl 32mg, Bupropion HCl 360mg). The dose will be titrated: 8 mg/90 mg on Week 1, 16 mg/180 mg on Week 2, 24 mg/270 mg on Week 3 and 32 mg/360 mg on Week 4. Dosing will continue for a total of 4 weeks during inpatient treatment, and thereafter for another month, with compliance monitored by smartphone.
干预措施: Contrave 8Mg-90Mg Extended-Release Tablet (Drug)
Bupropion
Participants will receive daily extended-release oral bupropion (Wellbutrin XL) at a dose of 450 mg. The dose will be titrated: 150 mg on Days 1 and 2, 300 mg on Days 3 and 4, and 450 mg on Day 5. Dosing will continue for a total of 4 weeks during inpatient treatment, and thereafter for another month, with compliance monitored by smartphone. A reduction to 300 mg will permitted to alleviate medication-related adverse effects if they occur.
干预措施: Bupropion (Drug)
结局指标
主要结局
Stimulant use 1 month after leaving inpatient treatment (self-report)
时间窗: 84 days
Stimulant use 1 month after leaving inpatient treatment, assessed via self-report. toxicology
Stimulant use 1 month after leaving inpatient treatment (urine toxicology)
时间窗: 84 days
Stimulant use 1 month after leaving inpatient treatment, assessed via urine sample.
次要结局
- Sustained attention(84 days)
- Working memory(84 days)
- Declarative memory(84 days)
- Inhibitory control - stop signal task(84 days)
- Inhibitory control - reversal learning(84 days)
- Reward-based decision-making(84 days)
- Decision making under risk and ambiguity(84 days)
- Loss Aversion(84 days)
研究者
Edythe London
Professor of Psychiatry and Biobehavioral Sciences and Molecular and Medical Pharmacology
University of California, Los Angeles