Alcohol Use DisorderNCT03037060
Exploring Regulation and Function of Dopamine D3 Receptors in Alcohol Use Disorders: A [11C]-(+)-PHNO Study
A study testing [11C]-(+)-PHNO PET scan, Alcohol Self-Administration and Craving Task in people with Alcohol Use Disorder, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Alcohol Use Disorder
- What is being tested?
- [11C]-(+)-PHNO PET scan, Alcohol Self-Administration and Craving Task
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteCanada
- Study dates
- Dec 2016to Aug 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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).
- Conditions
- Alcohol Use Disorder
- Being tested
- [11C]-(+)-PHNO PET scan, Alcohol Self-Administration, Craving Task, MRI scan, Neuropsychological Assessment
- Keywords
- Alcohol use, problem
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[11C]-(+)-PHNO PET scanOther
PET scan
Alcohol Self-AdministrationOther
Session for assessing motivation for consuming alcohol.
Craving TaskOther
Cue exposure paradigm
MRI scanOther
MRI scan scan to analyze the PET data will be administered.
Neuropsychological AssessmentOther
Cognitive questionnaires administered over course of study.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: [11C]-(+)-PHNO PET scan; Other: Alcohol Self-Administration; Other: Craving Task; Other: MRI scan; Other: Neuropsychological Assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: One PET scan after 2-7 days of abstinence from alcohol; ~2 hours in duration.
Secondary outcomes (2)
Alcohol craving ratings
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).
Measured: Cue paradigm session is expected to take ~1 hour and will occur on the PET day.
Effort to obtain alcohol
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.
Measured: Single self-administration session will occur on its own day with a time commitment of ~6 hours.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2017 (estimated)
- Study startDec 2016
- Primary completionAug 2020
- Study completionAug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alcohol Use DisorderStudies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bernard Le Foll, Centre for Addiction and Mental Health
- Investigators
- Bernard Le Foll, MD, PhD, Principal investigator, Centre for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03037060
- Sponsor's protocol ID
- 052/2016
- Status last verified
- Oct 2020
- First submitted
- 16 Jan 2017
- Last updated
- 29 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploring Regulation and Function of Dopamine D3 Receptors in Alcohol Use Disorders: A [11C]-(+)-PHNO Study
- ClinicalTrials.gov ID
- NCT03037060
- Acronym / sponsor ID
- 052/2016
- Conditions
- Alcohol Use Disorder
- Keywords
- Alcohol use, problem
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Study start
- Dec 2016 (actual)
- Primary completion
- Aug 2020 (actual)
- Study completion
- Aug 2020 (actual)
- First posted
- 31 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Other: [11C]-(+)-PHNO PET scan, Other: Alcohol Self-Administration, Other: Craving Task, Other: MRI scan, Other: Neuropsychological Assessment5 experimental sessions per participant: (1) [11C]-(+)-PHNO PET scan, (2), Alcohol Self-Administration, (3) Craving Task, (4) MRI scan and (5) Neuropsychological Assessment. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [11C]-(+)-PHNO PET scanPET scan | Other | Experimental |
| Alcohol Self-AdministrationSession for assessing motivation for consuming alcohol. | Other | Experimental |
| Craving TaskCue exposure paradigm | Other | Experimental |
| MRI scanMRI scan scan to analyze the PET data will be administered. | Other | Experimental |
| Neuropsychological AssessmentCognitive questionnaires administered over course of study. | Other | Experimental |
Primary outcome
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.
2 secondary outcomes
Alcohol craving ratings
Time frame: 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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2020.
- 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.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bernard Le Foll, MD, PhD principal investigator
Centre for Addiction and Mental Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing [11C]-(+)-PHNO PET scan, Alcohol Self-Administration and Craving Task in people with Alcohol Use Disorder, run by Centre for Addiction and Mental Health at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dopamine D2/D3 receptor occupancy (time frame: One PET scan after 2-7 days of abstinence from alcohol; ~2 hours in duration.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2020.