Dopamine Release in the Human Brain Following Alcohol Administration

Heavy Drinking Clinical Trial

Official title:

Imaging Alcohol Induced Dopamine Release in the Human Brain: a PET/[11C](+)PHNO Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01638364
• Other study ID #: 041/2012
• Status: Completed
• Phase: Phase 1
• First received: June 28, 2012
• Last updated: July 27, 2015
• Start date: January 2013
• Est. completion date: June 2015

Study information

• Verified date: July 2015
• Source: Centre for Addiction and Mental Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to examine whether there is an increase in dopamine levels in the human striatum following an oral administration of alcohol, as has been evidenced in animal models. This will be a Positron Emission Tomography (PET) study using the radiotracer, [11C]-(+)-PHNO (11C]-( + )-4-propyl- 3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol).

Description:

This will be a within subjects study in 8 heavy drinkers ages 21-45. The within factors will be PET scans following an alcoholic beverage and following a non-alcoholic beverage. Participants will also have a baseline session prior to the scans where they will complete various cognitive tasks and questionnaires. During each PET scan, subjective drug effects as well as heart rate, blood pressure, blood alcohol content and cortisol levels will be collected. The change in PHNO binding potential between the two scan conditions will be the primary outcome measure.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 21 Years to 45 Years

Eligibility

Inclusion Criteria:

• Healthy males and females of any ethnic origin between 21 and 45 years old.

• Reported consumption of at least two heavy drinking episodes (according to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) criterion of 5 drinks for males or 4 for females) in the past 30 days prior to assessment.

• Willing and capable to provide written informed consent

• Good command of the English language

Exclusion Criteria:

• Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnosis of alcohol dependence; receiving treatment for alcohol dependence

• Taking medications or have any medical condition for which alcohol is contraindicated

• Any medical condition requiring immediate investigation or treatment

• Previous head trauma/neurological condition such as clinically significant history of seizure disorder, a history of clinically significant head trauma (i.e., concussion resulting in clinically significant loss of consciousness) or past intracranial surgery

• Beck Depression Inventory score >16

• Current active or past suicidal ideation

• Pregnancy tested by urine and blood screen each PET study day or lactation

• Current DSM-IV diagnosis of any Axis I psychiatric disorder

• Regular use of any therapeutic or recreational psychoactive drug use during the last three months (with the exception of nicotine and alcohol) or other substance use disorder (including nicotine)

• Abnormal body mass (as defined as not within 20% of normal body mass index).

• Current past or anticipated exposure to radiation exceeding 20 mSv in the last year.

• Metal implants or paramagnetic objects within the body which may interfere with the magnetic resonance imaging (MRI).

• Claustrophobia or a history of panic attacks

• Abnormal clinical laboratory findings including serum creatinine greater than 2.0 mg/dl, abnormal liver function tests, elevated serum bilirubin (more than 1.5 times upper limit of normal), or pre-trial electrocardiogram (EKG) results demonstrating clinical significant abnormality

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Heavy Drinking

Intervention

Drug:
• alcoholic beverage
An appropriate amount of 95% USP ethyl alcohol will be mixed in orange juice and tonic water to obtain a drink equivalent to 3-5 standard drinks. The beverage will be consumed over a period of 15 minutes.
• non-alcoholic beverage
This beverage will be a mixture of orange juice and tonic water. The beverage will be consumed over a period of 15 minutes.

Locations

Country	Name	City	State
Canada	Centre for Addiction and Mental Health	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Centre for Addiction and Mental Health

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in PHNO Binding Potential	Following the injection of the positron-emitting radiotracer [11C]-(+)-PHNO, binding of this radiotracer to dopamine receptors (DR) D2/3 will be measured using the PET scanner. As dopamine also binds to DR D2/3, either an increase or decrease in dopamine levels will either decrease or increase PHNO occupancy respectively. [11C]-(+)-PHNO binding potential will be measured on two different conditions (alcoholic beverage vs non-alcoholic beverage) on two separate days.	2 weeks	No
Secondary	Subjective effects of alcohol	During the PET scans, the subjective effects ( Alcohol Urges Scale, Biphasic Alcohol Effects Scale)of alcohol will be assessed at various time points throughout beverage consumption and PET scan.	2 weeks	No
Secondary	Objective effects of alcohol	During the PET scans, the objective effects of alcohol (blood pressure, heart rate, blood alcohol content, blood cortisol levels) will be assessed at various time points throughout the drink consumption and PET scan.	2 weeks	No

External Links

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