TerminatedPhase 1

Dopamine D2/D3 Receptor Upregulation by Varenicline in Methamphetamine Users

Stopped: Global pandemic

United States62 participantsStarted 2018-01-11

Plain-language summary

While deficits in dopamine D2-type receptor availability have been linked to substance use disorders, higher availability associates with better behavioral treatment outcomes for stimulant dependence and resilience to addiction. Varenicline has been shown to upregulate D2-type receptors in drug-naive rats, and could be a useful therapeutic approach for the treatment of addictive disorders in humans. The purpose of the study is to assess the relationship between varenicline, dopamine signaling (specifically, D2-type receptor availability), functional connectivity within corticostriatal circuitry, genetic markers associated with smoking and methamphetamine abuse, and measures of cognitive performance. The investigators hypothesize that varenicline but not placebo will upregulate (increase) striatal dopamine D2-type receptor availability and improve cognition, and that the change in availability will correlate with the change in cognition. The investigators also hypothesize that varenicline but not placebo treatment will repair dysregulated connectivity between the striatum and prefrontal cortex observed in methamphetamine users, and will correlate with the change in cognition. The study design consists of two positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) scans to measure dopamine D2-type receptor availability and functional connectivity between the prefrontal cortex and striatum, two cognitive testing sessions including a battery of tests assessing working memory, declarative memory, sustained attention, inhibitory control, and reward-based decision making. Following eligibility screening, thirty six methamphetamine users will be enrolled and tested/scanned once prior to initiation of varenicline or placebo treatment and then again after completion of treatment.

Who can participate

Age range

18 Years – 60 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * English fluency in order to provide informed consent and complete questionnaires * Age of 18-60 years \[Children younger than 18 years will be excluded because of the potential risk of radiation exposure. Recruitment will be restricted to individuals within the first 5 decades of life to avoid effects of aging on DRD2/3 (dopamine type-2 receptor) BPND (binding potential). * Meeting DSM (Diagnostic and Statistical Manual of Mental Disorders) 5 criteria for stimulant-use disorder * Being within 2 weeks of admission to treatment and \< 2 months abstinent from stimulant use * Vital signs as follows: resting pulse between 50 and 95 beats per minute (bpm), blood pressures between 90-150 mm Hg (millimeter of mercury) systolic and 45-95 mm Hg diastolic * Hematology and chemistry laboratory test results within normal (+/- 10%) limits and normal kidney function (estimated glomerular filtration rate ≥ 90 ml/min/1.73m2) * Baseline ECG (electrocardiogram) demonstrating normal conduction (including QTc \[QT interval\]) 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. Exclusion Criteria: * History or evidence of seizure disorder or brain injury with loss of consciousness \>30 min * Previous adverse reaction to varenicline (VAR) * Neurological disorder that would compromis…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Dopamine D2-type receptor availability

Timeframe: 21 days

Trial details

NCT IDNCT03059563

SponsorUniversity of California, Los Angeles

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2023-09-28

View on ClinicalTrials.gov More Dopamine D2/3 Receptor Availability trials