Exploring Regulation and Function of Dopamine D3 Receptors in Alcohol Use Disorders: A [11C]-(+)-PHNO Study
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|ClinicalTrials.gov Identifier: NCT03037060|
Recruitment Status : Recruiting
First Posted : January 31, 2017
Last Update Posted : January 23, 2020
|Condition or disease||Intervention/treatment||Phase|
|Alcohol Use Disorder||Other: [11C]-(+)-PHNO PET scan Other: Alcohol Self-Administration Other: Craving Task Other: MRI scan Other: Neuropsychological Assessment||Not Applicable|
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 (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Exploring Regulation and Function of Dopamine D3 Receptors in Alcohol Use Disorders: A [11C]-(+)-PHNO Study|
|Study Start Date :||December 2016|
|Estimated Primary Completion Date :||September 2020|
|Estimated Study Completion Date :||September 2020|
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
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.
- 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.
- 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).
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03037060
|Contact: Bernard Le Foll, MD PhDemail@example.com|
|Contact: Saima Malik, PhDfirstname.lastname@example.org|
|Centre for Addiction and Mental Health||Recruiting|
|Toronto, Ontario, Canada, M5S2S1|
|Contact: Saima Malik, PhD 416-535-8501 email@example.com|
|Principal Investigator:||Bernard Le Foll, MD, PhD||Centre for Addiction and Mental Health|