Relapse Prevention in Stimulant Use Disorder

NCT04553263 | Withdrawn Early Phase 1 FDA Drug

• 1 other identifier: 20-001075
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Stimulant Use; Relapse; Cognitive Function; ADHD

Keywords

Stimulant Abuse; Relapse Prevention; ADHD; Contrave; Bupropion

Outcome Measures

Primary Outcomes (2)

• Stimulant use 1 month after leaving inpatient treatment (self-report)

  Stimulant use 1 month after leaving inpatient treatment, assessed via self-report. toxicology

  84 days

• Stimulant use 1 month after leaving inpatient treatment (urine toxicology)

  Stimulant use 1 month after leaving inpatient treatment, assessed via urine sample.

  84 days

Secondary Outcomes (8)

• 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

Other Outcomes (3)

• Personality - impulsivity

  84 days

• Personality - novelty seeking

  84 days

• Personality - reward dependence

  84 days

Study Arms (3)

Contrave

EXPERIMENTAL

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.

Drug: Contrave 8Mg-90Mg Extended-Release Tablet

Bupropion

EXPERIMENTAL

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.

Drug: Bupropion

Treatment As Usual

NO INTERVENTION

Participants will complete inpatient treatment as usual and will not receive any medication. This arm serves as a TAU control to compare outcomes versus Bupropion and Contrave arms.

Interventions

Contrave 8Mg-90Mg Extended-Release Tablet DRUG

Naltrexone HCl/Bupropion HCl is an FDA-approved weight-loss medication with efficacy via the mesolimbic dopamine system to reduce hunger and help control cravings.

Also known as: Naltrexone HCl/Bupropion HCl 8 Mg-90 Mg

Contrave

Bupropion DRUG

Bupropion is FDA-approved and marketed both as an antidepressant agent (Wellbutrin®) and treatment for smoking cessation (Zyban®) and has shown efficacy in reducing symptoms of depression and drug craving in stimulant users. it is also a promising candidate to improve cognition function.

Also known as: Wellbutrin, Zyban

Bupropion

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 %.

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

University of California Los Angeles

Los Angeles, California, 90024, United States

Location

MeSH Terms

Conditions

Recurrence; Attention Deficit Disorder with Hyperactivity

Interventions

bupropion hydrochloride, naltrexone hydrochoride drug combination; Bupropion

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propiophenones; Ketones; Organic Chemicals

Study Officials

• Edythe D London, Ph.D.

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry and Biobehavioral Sciences and Molecular and Medical Pharmacology

Study Record Dates

• First Submitted: June 3, 2020
• First Posted: September 17, 2020
• Study Start: June 11, 2023
• Primary Completion: January 11, 2025
• Study Completion: January 11, 2025
• Last Updated: September 22, 2023

Record last verified: 2023-09

Locations

US (1)