Alcohol Use DisorderEarly Phase 1Mu KappaNCT05957159
Investigating the Mu:Kappa Opioid Receptor Imbalance in Alcohol Use Disorder
A Early Phase 1 study testing Detoxification Program, PKAB and CFN in people with Alcohol Use Disorder, run by Yale University at 1 site in United States.
Trial summary
The primary objective of this multimodal positron emission tomography (PET) study is to use PET brain imaging to measure both MOR (Mu-Opioid receptors) and KOR (kappa-opioid receptors) in participants with alcohol use disorder (AUD) and to quantify the relationships between MOR and KOR, separately and jointly, to key… Read more about this study
- Who is it for?
- Ages 21 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Alcohol Use Disorder
- What is being tested?
- Detoxification Program, PKAB and CFN
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Nov 2023to 1 Nov 2028
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
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 21 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Participants with AUD will have a current diagnosis of AUD according to DSM-5 criteria (i.e., SCID-5 ascertained diagnosis, confirmed by the Principal Investigators);
- Participants with AUD will meet the following drinking criteria: males will drink > 14 drinks per week and exceed 4 drinks per day at least twice per week; females will drink > 7 drinks per week and exceed 3 drinks per day at least twice per week. They must meet drinking criteria during a consecutive 30-day period within the 90 days prior to intake;
- Participants with AUD will indicate willingness to abstain from alcohol and engage in a quit attempt;
- Healthy subjects will have no current or past diagnosis of AUD or other significant substance use disorder. They will drink less than 5 alcoholic drinks per week with no heavy drinking days (i.e., >4 drinks/day for men; >3 drinks/day for women) in the last 30 days;
- Able to read and write English and to provide voluntary, written informed consent;
- Agree to have blood drawn for genotyping of the OPRM1 which has been shown to impact the [11C]CFN outcome measure, BPND50.
Who cannot join
- Current significant medical condition such as neurological, cardiovascular, endocrine, renal, liver, or thyroid pathology that would impact the integrity of the data (note that elevated liver enzymes for individuals with AUD will not be exclusionary);
- Past or current neurological disorder or disorders affecting the brain including but not limited to multiple sclerosis, history of stroke, brain tumors, traumatic brain injury with loss of consciousness, seizure disorder;
- Current significant psychiatric disorder including severe substance use disorder (other than alcohol or tobacco use disorders*), and past or current psychotic symptoms;
- Regular use in the past 6 months of any prescription, psychoactive or herbal medications (e.g., antidepressants, antipsychotics, anxiolytics) that would impact the integrity of the data (e.g., naltrexone); No subject will be asked to stop taking medication to participate in the study;
- Women who are pregnant or nursing, or fail to use one of the following methods of birth control unless she or her partner is surgically sterile or she is postmenopausal (hormone contraceptives [oral, implant, injection, patch, or ring], contraceptive sponge, double barrier [diaphragm or condom plus spermicide], or IUD;
- Contraindications to MRI such as claustrophobia or metal in their body;
- Subjects whose participation would cause them to exceed yearly radiation limits for research subjects
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Yale University
New Haven, Connecticut, 06519
Kelly Cosgrove, PhD, 203-737-6969, kelly.cosgrove@yale.edu
Kelly Cosgrove, PhD
About this study
The primary objective of this multimodal positron emission tomography (PET) study is to use PET brain imaging to measure both MOR (Mu-Opioid receptors) and KOR (kappa-opioid receptors) in participants with alcohol use disorder (AUD) and to quantify the relationships between MOR and KOR, separately and jointly, to key clinical outcomes (e.g., craving, mood, withdrawal, time to lapse) during a quit attempt.
Read the detailed description
Primary Objective
The primary objective of this multimodal positron emission tomography (PET) study is to use PET brain imaging to measure both MOR (Mu-Opioid receptors) and KOR (kappa-opioid receptors) in participants with alcohol use disorder (AUD) and to quantify the relationships between MOR and KOR, separately and jointly, to key clinical outcomes (e.g., craving, mood, withdrawal, time to lapse) during a quit attempt. Investigators will achieve this goal by completing the following aims:
Aim 1: To determine whether participants with AUD in early abstinence (up to 6 days) have altered MOR and KOR availability compared to healthy subjects. Investigators propose to recruit 50 people with AUD (DSM-5 diagnosis) and 50 age- and sex-matched controls to each participate in one [11C]CFN and one [11C]PKAB PET scan. Participants with AUD will participate either 1) in a medically supervised inpatient unit, the Clinical Neuroscience Research Unit (CNRU), for ~6 days, or 2) will stop drinking on an outpatient basis with daily meetings for ~6 days. Measures of craving (including a cue reactivity task), mood, withdrawal, and drinking outcomes will be collected. Hypothesis: participants with AUD will have significantly higher MOR in ventral striatum, but lower KOR in amygdala and whole striatum compared to control participants.
Aim 2: To relate measures of MOR and KOR availability to clinical outcomes during early and late abstinence. Early abstinence (~6 days) will be followed by an outpatient quit attempt for an additional 3 weeks supported by contingency management. Measures of craving, mood, withdrawal, and drinking outcomes will be collected throughout the study. Hypothesis: Taken one at a time, MOR availability in ventral striatum as well as KOR in the amygdala and whole striatum will each be significantly associated with abstinence-induced craving, mood, withdrawal, and time to lapse in participants with AUD.
Aim 3: To maximize use of neuroimaging data via machine-learning-based clustering to identify biomarkers of the joint (MOR, KOR) dataset that characterize clinical outcomes in AUD during a quit attempt. Primary. The investigators will determine whether clusters of AUD patients based on features of the joint (MOR, KOR) data are significantly associated with distinct clinical outcomes (e.g., time to lapse) during a quit attempt. Secondary. Investigators will test the classification accuracy of our clustering approach. Hypotheses: Clustering of joint (MOR, KOR) data will yield clusters of AUD patients with significantly different clinical responses to a quit attempt. Clusters will be more compact (distinct) than if based on demographics or a single type of PET image, alone. A classification scheme based on (MOR, KOR) data will assign individual patients to pre-defined clusters with high classification accuracy, that is, to the cluster that best reflects their clinical outcomes.
Aim 4: To determine whether MOR and KOR availability normalizes over the course of abstinence. Subjects who do not drop out of the study in the first 3 weeks may return for one [11C]CFN, one [11C]PKAB PET scan, and one MRI during weeks 3-6 of the study. This will allow us to gain information on the changes in the MOR and KOR systems that occur during a quit attempt. Investigators hypothesize a reduction in MOR and increase in KOR within subject in participants who are able to maintain abstinence.
Secondary Objective (if applicable) The secondary objective of this study is to evaluate the predictive ability of the clustering method, i.e., its potential for personalized prediction of individual clinical outcomes. For any 'new' subject not used for the initial clustering, investigators will assign it to a cluster by a K-nearest neighbor approach.
- Conditions
- Alcohol Use Disorder
- Being tested
- Detoxification Program, PKAB, CFN
- Keywords
- Alcohol, Alcohol cessation
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Detoxification ProgramOther
Patients will begin inpatient or outpatient detoxification prior to completing imaging
PKABRadiation
90 PET Imaging Scan using [11C]LY2795050 (AKA [11C]PKAB)
CFNRadiation
90 Pet Imaging Scan using [11C]-Carfentanil
| Study group | Role | What they receive |
|---|---|---|
| Alcohol Use Disorder population completing Detoxification | Experimental | Subjects will be asked to complete both 90 minute [11C]CFN and 90 minute [11C]PKAB PET Imaging after 1-3 days of a detoxification program. Receives: Other: Detoxification Program; Radiation: PKAB; Radiation: CFN |
| Healthy Control population | Experimental | Subjects will be asked to complete both a 90 minute [11C]CFN and a 90 minute [11C]PKAB PET Imaging. Receives: Radiation: PKAB; Radiation: CFN |
What is being measured
The primary outcome is the main question the study is designed to answer.
Regional binding availability and volume of distribution of (Mu-Opioid receptors)
Time activity curves will be extracted from brain regions of interest during [11C]CFN PET Imaging. AUD subjects will be asked to complete this within first 6 days of abstinence. Healthy control subjects will be matched based on sex(Male/Female), smoking status (current/former/nonsmoker), and BMI (kg/m^2)
Measured: Within first 6 days of abstinence
Regional binding availability and volume of distribution of (Mu-Opioid receptors)
Time activity curves will be extracted from brain regions of interest during [11C]CFN PET Imaging. AUD subjects will be asked to complete this 3 -6 weeks into alcohol cessation. Healthy control subjects will be matched based on sex(Male/Female), smoking status (current/former/nonsmoker), and BMI (kg/m^2)
Measured: Between 3 to 6 weeks into alcohol cessation
Regional binding availability and volume of distribution of (Kappa-Opioid receptors)
Time activity curves will be extracted from brain regions of interest during [11C]PKAB PET Imaging. AUD subjects will be asked to complete this within first 6 days of abstinence. Healthy control subjects will be matched based on sex(Male/Female), smoking status (current/former/nonsmoker), and BMI (kg/m^2)
Measured: Within first 6 days of abstinence
Regional binding availability and volume of distribution of (Kappa-Opioid receptors)
Time activity curves will be extracted from brain regions of interest during [11C]PKAB PET Imaging. AUD subjects will be asked to complete this 3 -6 weeks into alcohol cessation. Healthy control subjects will be matched based on sex(Male/Female), smoking status (current/former/nonsmoker), and BMI (kg/m^2)
Measured: Between 3 to 6 weeks into alcohol cessation
Alcohol Cue Reactivity Craving
Investigators will follow the paradigm developed for the NIAAA Human Laboratory Medication Screening Program (HLAB). In the paradigm, participants will be first exposed to a glass of water and then to their typical alcoholic beverage, separated by a 90 second rest period. They will be instructed to not drink but to sniff the beverages for a fixed duration. Immediately after, alcohol craving and beverage liking will be assessed. AUD subjects will be asked to complete this within first 6 days of abstinence. Healthy control subjects will be matched based on sex(Male/Female), smoking status (current/former/nonsmoker), and BMI (kg/m^2)
Measured: Within first 6 days of abstinence
Change in Alcohol Withdrawal
Withdrawal will be assessed using The Clinical Institute Withdrawal Assessment (CIWA-R)64. AUD and Healthy controls will be asked to complete this paper questionnaire up to 1 month prior to CFN and PKAB PET Imaging and once again up to 6 days into alcohol cessation for AUD population
Range: 0- 67, higher scores indicating more symptoms of withdrawal.
Measured: Up to 1 month prior to initial imaging and up to 6 days into alcohol cessation
Change in Alcohol Use
Assessed using the TimeLine Followback (TLFB)62 and BACtrack Skyn; AUD and Healthy controls will be asked to complete this paper questionnaire up to 1 month prior to CFN and PKAB PET Imaging and once again up to 6 days into alcohol cessation for AUD population.
Calendar style open ended.
Minimum 0 alcohol uses in past month -31 sittings of alcohol in past month
Measured: Up to 1 month prior to initial imaging and up to 6 days into alcohol cessation
Change in Alcohol Craving
Craving will be assessed with Alcohol Craving Scale (ACS, adapted from Singleton et al.63),
Range: 47 to 329, higher scores indicate higher craving to alcohol
Measured: Up to 1 month prior to initial imaging and up to 6 days into alcohol cessation
Change in Mood
Mood, anhedonia symptoms will be assessed with the Center for Epidemiologic Studies Depression Scale (CES-D) Range : 0 to 60. Higher scores indicate more symptoms of depression.
Measured: Up to 1 month prior to initial imaging and up to 6 days into alcohol cessation
Secondary outcomes (14)
Baseline Verbal Memory
Cogstate International Shopping List Task - a computerized task to assess verbal learning and memory.
# of correctly recalled items from a grocery list (3 trials). Verbal Recalled item from grocery list after delay (1 trial; higher ~better memory/recall)
Range: up to 0 to 36 errors (per trial), up to 108 errors for all 3 trials.
Measured: Up to 3 months prior to initial imaging or on initial imaging day (depending hospital availability
Baseline Verbal Memory
Cogstate International Shopping List Task - a computerized task to assess verbal learning and memory.
# of correctly recalled items from a grocery list (3 trials). Verbal Recalled item from grocery list after delay (1 trial; higher ~better memory/recall)
Range: 0 to 36 errors (per trial), up to 108 errors for all 3 trials.
Measured: Completed on second PKAB/CFN imaging day (Between 3 to 6 weeks into alcohol cessation)
Baseline Executive Function
: Cogstate Groton Maze Learning Task - a computerized task to assess executive function and spatial problem solving. # of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function.
Range: 0-140 errors per trial, 0- 700 errors for all five trials
Measured: Up to 3 months prior to initial imaging or on initial imaging day (depending hospital availability
Test Executive Function
: Cogstate Groton Maze Learning Task - a computerized task to assess executive function and spatial problem solving. # of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function.
Range: 0-140 errors per trial, 0- 700 errors for all five trials
Measured: Completed on second PKAB/CFN imaging day (Between 3 to 6 weeks into alcohol cessation)
Baseline Visual Processing Speed
Cogstate Detection Task - a computerized task to assess psychomotor function and speed of processing. Visual -motor processing speed: response latency to detect a card flipped over (log10(ms); higher~ worse processing speed).
Range: 0 milliseconds - 30 minute times out.
Measured: Up to 3 months prior to initial imaging or on initial imaging day (depending hospital availability
Test Visual Processing Speed
Cogstate Detection Task - a computerized task to assess psychomotor function and speed of processing. Visual -motor processing speed: response latency to detect a card flipped over (log10(ms); higher~ worse processing speed).
Range: 0 milliseconds - 30 minute times out.
Measured: Completed on second PKAB/CFN imaging day (Between 3 to 6 weeks into alcohol cessation)
Baseline Visual Attention
Identification Task - a computerized task to assess visual attention and vigilance. Response latency to identify card color (log10(ms)higher ~worse attention)
Range: 0 milliseconds - 30 minute times out.
Measured: Up to 3 months prior to initial imaging or on initial imaging day (depending hospital availability
Test Visual Attention
Identification Task - a computerized task to assess visual attention and vigilance. Response latency to identify card color (log10(ms)higher ~worse attention)
Range: 0 milliseconds - 30 minute times out.
Measured: Completed on second PKAB/CFN imaging day (Between 3 to 6 weeks into alcohol cessation)
Baseline Visual Learning
One Card Learning Task - a computerized task to assess visual learning and memory. Visual Learning: % of correctly identified repeat cards (arcsine% correct); higher ~ better learning.
Range: 66-88 cards
Measured: Up to 3 months prior to initial imaging or on initial imaging day (depending hospital availability
Test Visual Learning
One Card Learning Task - a computerized task to assess visual learning and memory. Visual Learning: % of correctly identified repeat cards (arcsine% correct); higher ~ better learning.
Range: 66-88
Measured: Completed on second PKAB/CFN imaging day (Between 3 to 6 weeks into alcohol cessation)
Baseline Working Memory One Back
One Back Task - computerized tasks to assess attention and working memory. Working memory: % of correctly identified cards that matched the card presented either one card previously (arcsine(% correct); Higher~ better working memory
Range: ONB 24-31,
Measured: Up to 3 months prior to initial imaging or on initial imaging day (depending hospital availability
Test Working Memory One Back
One Back Task - computerized tasks to assess attention and working memory. Working memory: % of correctly identified cards that matched the card presented either one card previously (arcsine(% correct); Higher~ better working memory
Range: ONB 24-31
Measured: Completed on second PKAB/CFN imaging day (Between 3 to 6 weeks into alcohol cessation)
Baseline Working Memory Two Back
One Back Task - computerized tasks to assess attention and working memory. Working memory: % of correctly identified cards that matched the card presented either one card previously (arcsine(% correct); Higher~ better working memory
Range: Two Back 24-32
Measured: Up to 3 months prior to initial imaging or on initial imaging day (depending hospital availability
Test Working Memory Two Back
Two Back Task - computerized tasks to assess attention and working memory. Working memory: % of correctly identified cards that matched the card presented either one card previously (arcsine(% correct); Higher~ better working memory
Range: Two Back 24-32
Measured: Completed on second PKAB/CFN imaging day (Between 3 to 6 weeks into alcohol cessation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2023
- Study start7 Nov 2023
- Primary completion1 Aug 2028 (estimated)
- Study completion1 Nov 2028 (estimated)
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 Yale UniversityThe 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- All subjects will be asked to complete both PKAB and CFN PET Imaging scans, AUD subset will participate in a detoxification program
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Principal investigator, Kelly Cosgrove, Yale University
- Investigators
- Kelly Cosgrove, PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05957159
- Sponsor's protocol ID
- 2000035344
- Other IDs
- 1R01AA030528-01A1
- Acronym
- Mu Kappa
- Status last verified
- Sep 2026
- First submitted
- 15 Jun 2023
- Last updated
- 9 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Mu:Kappa Opioid Receptor Imbalance in Alcohol Use Disorder
- ClinicalTrials.gov ID
- NCT05957159
- Acronym / sponsor ID
- Mu Kappa / 2000035344
- Conditions
- Alcohol Use Disorder
- Keywords
- Alcohol, Alcohol cessation
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- 7 Nov 2023 (actual)
- Primary completion
- 1 Aug 2028 (estimated)
- Study completion
- 1 Nov 2028 (estimated)
- First posted
- 24 Jul 2023 (actual)
- 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.
The primary objective of this multimodal positron emission tomography (PET) study is to use PET brain imaging to measure both MOR (Mu-Opioid receptors) and KOR (kappa-opioid receptors) in participants with alcohol use disorder (AUD) and to quantify the relationships between MOR and KOR, separately and jointly, to key clinical outcomes (e.g., craving, mood, withdrawal, time to lapse) during a quit attempt.
Detailed description
Primary Objective
The primary objective of this multimodal positron emission tomography (PET) study is to use PET brain imaging to measure both MOR (Mu-Opioid receptors) and KOR (kappa-opioid receptors) in participants with alcohol use disorder (AUD) and to quantify the relationships between MOR and KOR, separately and jointly, to key clinical outcomes (e.g., craving, mood, withdrawal, time to lapse) during a quit attempt. Investigators will achieve this goal by completing the following aims:
Aim 1: To determine whether participants with AUD in early abstinence (up to 6 days) have altered MOR and KOR availability compared to healthy subjects. Investigators propose to recruit 50 people with AUD (DSM-5 diagnosis) and 50 age- and sex-matched controls to each participate in one [11C]CFN and one [11C]PKAB PET scan. Participants with AUD will participate either 1) in a medically supervised inpatient unit, the Clinical Neuroscience Research Unit (CNRU), for ~6 days, or 2) will stop drinking on an outpatient basis with daily meetings for ~6 days. Measures of craving (including a cue reactivity task), mood, withdrawal, and drinking outcomes will be collected. Hypothesis: participants with AUD will have significantly higher MOR in ventral striatum, but lower KOR in amygdala and whole striatum compared to control participants.
Aim 2: To relate measures of MOR and KOR availability to clinical outcomes during early and late abstinence. Early abstinence (~6 days) will be followed by an outpatient quit attempt for an additional 3 weeks supported by contingency management. Measures of craving, mood, withdrawal, and drinking outcomes will be collected throughout the study. Hypothesis: Taken one at a time, MOR availability in ventral striatum as well as KOR in the amygdala and whole striatum will each be significantly associated with abstinence-induced craving, mood, withdrawal, and time to lapse in participants with AUD.
Aim 3: To maximize use of neuroimaging data via machine-learning-based clustering to identify biomarkers of the joint (MOR, KOR) dataset that characterize clinical outcomes in AUD during a quit attempt. Primary. The investigators will determine whether clusters of AUD patients based on features of the joint (MOR, KOR) data are significantly associated with distinct clinical outcomes (e.g., time to lapse) during a quit attempt. Secondary. Investigators will test the classification accuracy of our clustering approach. Hypotheses: Clustering of joint (MOR, KOR) data will yield clusters of AUD patients with significantly different clinical responses to a quit attempt. Clusters will be more compact (distinct) than if based on demographics or a single type of PET image, alone. A classification scheme based on (MOR, KOR) data will assign individual patients to pre-defined clusters with high classification accuracy, that is, to the cluster that best reflects their clinical outcomes.
Aim 4: To determine whether MOR and KOR availability normalizes over the course of abstinence. Subjects who do not drop out of the study in the first 3 weeks may return for one [11C]CFN, one [11C]PKAB PET scan, and one MRI during weeks 3-6 of the study. This will allow us to gain information on the changes in the MOR and KOR systems that occur during a quit attempt. Investigators hypothesize a reduction in MOR and increase in KOR within subject in participants who are able to maintain abstinence.
Secondary Objective (if applicable) The secondary objective of this study is to evaluate the predictive ability of the clustering method, i.e., its potential for personalized prediction of individual clinical outcomes. For any 'new' subject not used for the initial clustering, investigators will assign it to a cluster by a K-nearest neighbor approach.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- All subjects will be asked to complete both PKAB and CFN PET Imaging scans, AUD subset will participate in a detoxification program
| Arm | Type | Receives |
|---|---|---|
| Alcohol Use Disorder population completing Detoxification | Experimental | Other: Detoxification Program, Radiation: PKAB, Radiation: CFNSubjects will be asked to complete both 90 minute [11C]CFN and 90 minute [11C]PKAB PET Imaging after 1-3 days of a detoxification program. |
| Healthy Control population | Experimental | Radiation: PKAB, Radiation: CFNSubjects will be asked to complete both a 90 minute [11C]CFN and a 90 minute [11C]PKAB PET Imaging. |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Participants with AUD will have a current diagnosis of AUD according to DSM-5 criteria (i.e., SCID-5 ascertained diagnosis, confirmed by the Principal Investigators);
- Participants with AUD will meet the following drinking criteria: males will drink > 14 drinks per week and exceed 4 drinks per day at least twice per week; females will drink > 7 drinks per week and exceed 3 drinks per day at least twice per week. They must meet drinking criteria during a consecutive 30-day period within the 90 days prior to intake;
- Participants with AUD will indicate willingness to abstain from alcohol and engage in a quit attempt;
- Healthy subjects will have no current or past diagnosis of AUD or other significant substance use disorder. They will drink less than 5 alcoholic drinks per week with no heavy drinking days (i.e., >4 drinks/day for men; >3 drinks/day for women) in the last 30 days;
- Able to read and write English and to provide voluntary, written informed consent;
Key exclusion criteria (7 listed)
- Current significant medical condition such as neurological, cardiovascular, endocrine, renal, liver, or thyroid pathology that would impact the integrity of the data (note that elevated liver enzymes for individuals with AUD will not be exclusionary);
- Past or current neurological disorder or disorders affecting the brain including but not limited to multiple sclerosis, history of stroke, brain tumors, traumatic brain injury with loss of consciousness, seizure disorder;
- Current significant psychiatric disorder including severe substance use disorder (other than alcohol or tobacco use disorders*), and past or current psychotic symptoms;
- Regular use in the past 6 months of any prescription, psychoactive or herbal medications (e.g., antidepressants, antipsychotics, anxiolytics) that would impact the integrity of the data (e.g., naltrexone); No subject will be asked to stop taking medication to participate in the study;
- Women who are pregnant or nursing, or fail to use one of the following methods of birth control unless she or her partner is surgically sterile or she is postmenopausal (hormone contraceptives [oral, implant, injection, patch, or ring], contraceptive sponge, double barrier [diaphragm or condom plus spermicide], or IUD;
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 |
|---|---|---|
| Detoxification ProgramPatients will begin inpatient or outpatient detoxification prior to completing imaging | Other | Alcohol Use Disorder population completing Detoxification |
| PKAB90 PET Imaging Scan using [11C]LY2795050 (AKA [11C]PKAB) | Radiation | Alcohol Use Disorder population completing Detoxification, Healthy Control population |
| CFN90 Pet Imaging Scan using [11C]-Carfentanil | Radiation | Alcohol Use Disorder population completing Detoxification, Healthy Control population |
Primary outcome
Regional binding availability and volume of distribution of (Mu-Opioid receptors)
Time frame: Within first 6 days of abstinence
Time activity curves will be extracted from brain regions of interest during [11C]CFN PET Imaging. AUD subjects will be asked to complete this within first 6 days of abstinence. Healthy control subjects will be matched based on sex(Male/Female), smoking status (current/former/nonsmoker), and BMI (kg/m^2)
Regional binding availability and volume of distribution of (Mu-Opioid receptors)
Time frame: Between 3 to 6 weeks into alcohol cessation
Time activity curves will be extracted from brain regions of interest during [11C]CFN PET Imaging. AUD subjects will be asked to complete this 3 -6 weeks into alcohol cessation. Healthy control subjects will be matched based on sex(Male/Female), smoking status (current/former/nonsmoker), and BMI (kg/m^2)
Regional binding availability and volume of distribution of (Kappa-Opioid receptors)
Time frame: Within first 6 days of abstinence
Time activity curves will be extracted from brain regions of interest during [11C]PKAB PET Imaging. AUD subjects will be asked to complete this within first 6 days of abstinence. Healthy control subjects will be matched based on sex(Male/Female), smoking status (current/former/nonsmoker), and BMI (kg/m^2)
Regional binding availability and volume of distribution of (Kappa-Opioid receptors)
Time frame: Between 3 to 6 weeks into alcohol cessation
Time activity curves will be extracted from brain regions of interest during [11C]PKAB PET Imaging. AUD subjects will be asked to complete this 3 -6 weeks into alcohol cessation. Healthy control subjects will be matched based on sex(Male/Female), smoking status (current/former/nonsmoker), and BMI (kg/m^2)
Alcohol Cue Reactivity Craving
Time frame: Within first 6 days of abstinence
Investigators will follow the paradigm developed for the NIAAA Human Laboratory Medication Screening Program (HLAB). In the paradigm, participants will be first exposed to a glass of water and then to their typical alcoholic beverage, separated by a 90 second rest period. They will be instructed to not drink but to sniff the beverages for a fixed duration. Immediately after, alcohol craving and beverage liking will be assessed. AUD subjects will be asked to complete this within first 6 days of abstinence. Healthy control subjects will be matched based on sex(Male/Female), smoking status (current/former/nonsmoker), and BMI (kg/m^2)
Change in Alcohol Withdrawal
Time frame: Up to 1 month prior to initial imaging and up to 6 days into alcohol cessation
Withdrawal will be assessed using The Clinical Institute Withdrawal Assessment (CIWA-R)64. AUD and Healthy controls will be asked to complete this paper questionnaire up to 1 month prior to CFN and PKAB PET Imaging and once again up to 6 days into alcohol cessation for AUD population Range: 0- 67, higher scores indicating more symptoms of withdrawal.
Change in Alcohol Use
Time frame: Up to 1 month prior to initial imaging and up to 6 days into alcohol cessation
Assessed using the TimeLine Followback (TLFB)62 and BACtrack Skyn; AUD and Healthy controls will be asked to complete this paper questionnaire up to 1 month prior to CFN and PKAB PET Imaging and once again up to 6 days into alcohol cessation for AUD population. Calendar style open ended. Minimum 0 alcohol uses in past month -31 sittings of alcohol in past month
Change in Alcohol Craving
Time frame: Up to 1 month prior to initial imaging and up to 6 days into alcohol cessation
Craving will be assessed with Alcohol Craving Scale (ACS, adapted from Singleton et al.63), Range: 47 to 329, higher scores indicate higher craving to alcohol
Change in Mood
Time frame: Up to 1 month prior to initial imaging and up to 6 days into alcohol cessation
Mood, anhedonia symptoms will be assessed with the Center for Epidemiologic Studies Depression Scale (CES-D) Range : 0 to 60. Higher scores indicate more symptoms of depression.
14 secondary outcomes
Baseline Verbal Memory
Time frame: Up to 3 months prior to initial imaging or on initial imaging day (depending hospital availability
Baseline Verbal Memory
Time frame: Completed on second PKAB/CFN imaging day (Between 3 to 6 weeks into alcohol cessation)
Baseline Executive Function
Time frame: Up to 3 months prior to initial imaging or on initial imaging day (depending hospital availability
Test Executive Function
Time frame: Completed on second PKAB/CFN imaging day (Between 3 to 6 weeks into alcohol cessation)
Baseline Visual Processing Speed
Time frame: Up to 3 months prior to initial imaging or on initial imaging day (depending hospital availability
Test Visual Processing Speed
Time frame: Completed on second PKAB/CFN imaging day (Between 3 to 6 weeks into alcohol cessation)
Baseline Visual Attention
Time frame: Up to 3 months prior to initial imaging or on initial imaging day (depending hospital availability
Test Visual Attention
Time frame: Completed on second PKAB/CFN imaging day (Between 3 to 6 weeks into alcohol cessation)
Baseline Visual Learning
Time frame: Up to 3 months prior to initial imaging or on initial imaging day (depending hospital availability
Test Visual Learning
Time frame: Completed on second PKAB/CFN imaging day (Between 3 to 6 weeks into alcohol cessation)
Baseline Working Memory One Back
Time frame: Up to 3 months prior to initial imaging or on initial imaging day (depending hospital availability
Test Working Memory One Back
Time frame: Completed on second PKAB/CFN imaging day (Between 3 to 6 weeks into alcohol cessation)
Baseline Working Memory Two Back
Time frame: Up to 3 months prior to initial imaging or on initial imaging day (depending hospital availability
Test Working Memory Two Back
Time frame: Completed on second PKAB/CFN imaging day (Between 3 to 6 weeks into alcohol cessation)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2026.
- 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.
Kelly Cosgrove, PhD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Detoxification Program, PKAB and CFN in people with Alcohol Use Disorder, run by Yale University at 1 site in United States.
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 7 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: looking for participants now, as of the sponsor's last update on 9 Sep 2026. 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 United States. 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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marc Grasso (2037375083, marc.grasso@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Regional binding availability and volume of distribution of (Mu-Opioid receptors) (time frame: Within first 6 days of abstinence). The study lists 9 primary outcomes in all. 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 9 Sep 2026.