NCT05957159 · Yale University
Investigating the Mu:Kappa Opioid Receptor Imbalance in Alcohol Use Disorder
(Mu Kappa)
What this study is about
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.
View original scientific description
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.
Interventions
OTHER
Detoxification Program
Patients will begin inpatient or outpatient detoxification prior to completing imaging
RADIATION
PKAB
90 PET Imaging Scan using \[11C\]LY2795050 (AKA \[11C\]PKAB)
RADIATION
CFN
90 Pet Imaging Scan using \[11C\]-Carfentanil
Primary outcome measures
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- 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.
Exclusion criteria
- 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
Where
- New Haven, Connecticut
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
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Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Apr 1, 2025 · Source of record for eligibility and locations