Clinical trial NCT03059563: Dopamine D2/D3 Receptor Upregulation by Varenicline in Methamphetamine Users
Official title: Dopamine D2/D3 Receptor Upregulation by Varenicline in Methamphetamine Users
Conditions: Dopamine D2/3 Receptor Availability
Cognitive Function
Methamphetamine Abuse
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.
Interventions:
description: Varenicline is an FDA-approved medication to facilitate smoking cessation. it is also a promising candidate to enhance dopamine signaling by upregulating dopamine D2/D3 (type 2) receptors in the striatum and improve cognitive function.
name: Varenicline
other_name: Chantix
type: Drug
description: A placebo containing no active ingredients will be used as a control to assess the effects of varenicline on dopamine D2/D3 receptor availability and cognitive function.
name: Placebo
type: Other
Study arms:
design_group_description: A standard dose titration regimen that is used for smoking-cessation will be followed. The pharmacist will prepare capsules of varenicline for each week of study participation. Under observation by a study clinician, participants will receive one capsule containing 0.5 mg VAR each day (0900 h) for 3 days, then one capsule containing 0.5 mg VAR twice daily (0900 h, 2100 h) for 4 days, and finally a capsule containing 1 mg VAR twice daily (0900 h, 2100 h) for the next 2 weeks.
design_group_title: Varenicline
design_group_type: Experimental
design_group_description: The same procedure used for varenicline treatment will be followed. The pharmacist will prepare capsules of placebo for each week of study participation. Under observation by a study clinician, participants will receive one capsule containing placebo each day (0900 h) for 3 days, then one capsule containing placebo twice daily (0900 h, 2100 h) for 4 days, and finally a capsule containing placebo twice daily (0900 h, 2100 h) for the next 2 weeks.
design_group_title: Placebo
design_group_type: Placebo Comparator
Sponsor: University of California, Los Angeles
Collaborators: National Institute on Drug Abuse
Drug name mappings:
name: 酒石酸伐尼克兰
lang: CN
name: Varenicline Tartrate
lang: EN
name: バレニクリン酒石酸塩
lang: JP