Relapse Prevention in Stimulant Use Disorder

• Status: Not yet recruiting
• Trial end date: 2023-01-11
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, Los Angeles
• Treatments: Bupropion; Bupropion hydrochloride, naltrexone hydrochoride drug combination; Naltrexone

Criteria

Inclusion Criteria:

1. English fluency (in order to provide informed consent and complete questionnaires)

2. Age of 18-65 years inclusive

3. Meeting DSM 5 criteria for Stimulant-use disorder

4. Being 2-8 weeks abstinent from drugs of abuse other than nicotine (in cigarettes)

5. 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)

6. 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.

7. Baseline ECG demonstrating normal conduction (including QTc) without clinically significant arrhythmias

8. 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.

9. Entering into and remaining in treatment voluntarily.

Exclusion Criteria:

1. Age of <18 or >65 years.

2. 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

3. 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

4. Prior therapy with any opiate-substitutes (methadone, LAAM, buprenorphine) within 2 months of enrollment.

5. Previous adverse reaction to Bupropion or Naltrexone.

6. 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

7. MAO-I use in the 2 weeks before enrollment

8. Disease or injury preventing use of both eyes and ability to complete computer tasks assessing cognitive function (e.g. glaucoma, colorblindness)

9. Brain injury with loss of consciousness >30 min

10. 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.

11. Electroconvulsive therapy within the 90 days before screening.

12. Current suicidal ideation or plan, as assessed by the MINI

13. 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).

14. 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]

15. 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 %.

16. 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.

17. Neurological disorder that would compromise informed consent or complicate data interpretation (e.g., organic brain disease or dementia).

18. Any condition that, as deemed by the investigators and study physician, would compromise safe participation.

19. 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.