Exploring Regulation and Function of Dopamine D3 Receptors in Alcohol Use Disorders: A [11C]-(+)-PHNO Study

NCT03037060 | Completed

• 1 other identifier: 052/2016
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

There is a need to better understand the mechanisms underlying alcohol use and dependence in order to advance the clinical treatment of alcohol dependence. Here, the investigators will use Positron Emission Tomography to determine if there is an up-regulation of D3 receptors in the brains of subjects with alcohol use disorders. The investigators will also investigate the relationship between D3 binding and major phenotypes associated with alcohol use disorders, namely: alcohol cue induced craving and motivation to self-administer alcohol in the laboratory.

Conditions

Alcohol Use Disorder

Keywords

Alcohol use, problem

Outcome Measures

Primary Outcomes (1)

• Dopamine D2/D3 receptor occupancy

  Dopamine D2/D3 receptor occupancy in the brains of individuals with Alcohol Use Disorders will be quantified using \[11C\]-(+)-PHNO Positron Emission Tomography (PET). \[11C\]-(+)-PHNO binding levels will be used to infer receptor occupancy.

  One PET scan after 2-7 days of abstinence from alcohol; ~2 hours in duration.

Secondary Outcomes (2)

• Alcohol craving ratings

  Cue paradigm session is expected to take ~1 hour and will occur on the PET day.

• Effort to obtain alcohol

  Single self-administration session will occur on its own day with a time commitment of ~6 hours.

Study Arms (1)

Experimental

EXPERIMENTAL

5 experimental sessions per participant: (1) \[11C\]-(+)-PHNO PET scan, (2), Alcohol Self-Administration, (3) Craving Task, (4) MRI scan and (5) Neuropsychological Assessment.

Other: [11C]-(+)-PHNO PET scan; Other: Alcohol Self-Administration; Other: Craving Task; Other: MRI scan; Other: Neuropsychological Assessment

Interventions

[11C]-(+)-PHNO PET scan OTHER

PET scan

Experimental

Alcohol Self-Administration OTHER

Session for assessing motivation for consuming alcohol.

Experimental

Craving Task OTHER

Cue exposure paradigm

Experimental

MRI scan OTHER

MRI scan scan to analyze the PET data will be administered.

Experimental

Neuropsychological Assessment OTHER

Cognitive questionnaires administered over course of study.

Experimental

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects will meet diagnostic criteria for alcohol use disorder (mild through severe).
• Willing to abstain from drugs and alcohol prior to study visits
• A negative urine screen for illicit psychoactive drug use
• Willing and capable to provide written informed consent
• Willing to participate in cue exposure and intravenous alcohol administration sessions
• Male and female adults (at least 19 years old)

You may not qualify if:

• DSM diagnosis of drug dependence other than alcohol
• Any severe Axis I disorder aside from alcohol use disorder
• Any medical condition requiring immediate investigation
• History of seizures, past or current neurological illness or serious head trauma
• Suicidal ideation
• Pregnancy tested by urine or blood screen or lactation
• Current past or anticipated exposure to radiation exceeding permissible limits as set by the CAMH PET Centre
• Metal implants or paramagnetic objects within the body which may interfere with the MRI
• Claustrophobia or a history of panic attacks
• Any other problem that, in the investigators' opinion, would preclude participation in trial (i.e., complicated withdrawal).
• Currently seeking treatment or attempting to reduce/quit drinking
• History of negative responses to venipuncture procedures (e.g., fainting/vasovagal response)
• Medications or medical disorders for which alcohol consumption is contraindicated

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M5S2S1, Canada

Location

Related Links

• Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching hospital, fully affiliated with the University of Toronto, and a PAHO/WHO Collaborating Centre.

MeSH Terms

Conditions

Alcoholism

Interventions

Ethanol; Magnetic Resonance Spectroscopy; Neuropsychological Tests

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Alcohols; Organic Chemicals; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Psychological Tests; Behavioral Disciplines and Activities

Study Officials

• Bernard Le Foll, MD, PhD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, MD, PhD, CCFP

Study Record Dates

• First Submitted: January 16, 2017
• First Posted: January 31, 2017
• Study Start: December 1, 2016
• Primary Completion: August 1, 2020
• Study Completion: August 1, 2020
• Last Updated: October 29, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)