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

October 27, 2020 updated by: Bernard Le Foll, Centre for Addiction and Mental Health
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Alcohol dependence is a devastating illness with social and medical costs estimated to be 180 billion dollars annually in the US. In the clinical treatment of alcoholism, reducing alcohol consumption in heavy drinkers is a major clinical challenge. As such, there has been much emphasis in both clinical and preclinical research to identify the substrates that mediate craving, excessive drinking and addiction. Identifying the neurobiological mechanisms of alcohol dependence may lead to the development of new and better treatment strategies. Preclinical studies indicate that the D3 receptor is involved in alcohol-cue response and in the motivation to drink alcohol. However, there is currently no data available in human subjects exploring the relationship between D3 and those behavioral responses in subjects with alcohol use disorders.

Aim #1: To measure the [11C]-(+)-PHNO PET binding levels in the brains of subjects with alcohol use disorders.

Aim #2: To determine the relationship between D3 receptor binding and alcohol cue induced craving and motivation to self-administer alcohol in the laboratory.

To achieve designated goals, the investigators will recruit 25 male and female subjects who are non-treatment seekers. After a period of abstinence from alcohol, participants will come to the Centre for Addiction of Mental Health for a [11C]-(+)-PHNO PET scan. Participants will also have additional sessions during which other alcohol-related measures will be assessed (i.e. alcohol cue induced craving and motivation to self-administer alcohol in the laboratory).

Study Type

Interventional

Enrollment (Actual)

17

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5S2S1
        • Centre for Addiction and Mental Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
PET scan
Other: Alcohol Self-Administration
Session for assessing motivation for consuming alcohol.
Other: Craving Task
Cue exposure paradigm
Other: MRI scan
MRI scan scan to analyze the PET data will be administered.
Other: Neuropsychological Assessment
Cognitive questionnaires administered over course of study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dopamine D2/D3 receptor occupancy
Time Frame: One PET scan after 2-7 days of abstinence from alcohol; ~2 hours in duration.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Alcohol craving ratings
Time Frame: Cue paradigm session is expected to take ~1 hour and will occur on the PET day.
Participants' ratings for alcohol craving acquired during the validated Cue-Induced Craving Paradigm (using the Alcohol Urge Questionnaire: 8 items on a 11-point Likert scale) will be correlated to dopamine receptor occupancy (outcome 1).
Cue paradigm session is expected to take ~1 hour and will occur on the PET day.
Effort to obtain alcohol
Time Frame: Single self-administration session will occur on its own day with a time commitment of ~6 hours.
Laboratory alcohol self-administration paradigm in which participants press a button to intravenously self-administer small doses of alcohol will be used to assess amount of effort expended to obtain alcohol ("break point"). The # of button presses required to obtain the alcohol will increase as per the Progressive Ratio schedule. Regression analysis between effort and [11C]-(+)-PHNO binding (outcome 1) will be applied.
Single self-administration session will occur on its own day with a time commitment of ~6 hours.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre for Addiction and Mental Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2016

Primary Completion (Actual)

August 1, 2020

Study Completion (Actual)

August 1, 2020

Study Registration Dates

First Submitted

January 16, 2017

First Submitted That Met QC Criteria

January 27, 2017

First Posted (Estimate)

January 31, 2017

Study Record Updates

Last Update Posted (Actual)

October 29, 2020

Last Update Submitted That Met QC Criteria

October 27, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 052/2016

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Alcohol Use Disorder

Clinical Trials on [11C]-(+)-PHNO PET scan

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Bahamas

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe