Investigating the Mu:Kappa Opioid Receptor Imbalance in Alcohol Use Disorder

NCT05957159 | Recruiting Early Phase 1 FDA Drug

• 2 other identifiers: 20000353441R01AA030528-01A1
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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 clinical outcomes (e.g., craving, mood, withdrawal, time to lapse) during a quit attempt.

Conditions

Alcohol Use Disorder

Keywords

Alcohol; Alcohol cessation

Outcome Measures

Primary Outcomes (9)

• 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)

  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)

  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)

  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)

  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)

  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.

  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

  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

  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.

  Up to 1 month prior to initial imaging and up to 6 days into alcohol cessation

Secondary Outcomes (14)

• Baseline Verbal Memory

  Up to 3 months prior to initial imaging or on initial imaging day (depending hospital availability

• Baseline Verbal Memory

  Completed on second PKAB/CFN imaging day (Between 3 to 6 weeks into alcohol cessation)

• Baseline Executive Function

  Up to 3 months prior to initial imaging or on initial imaging day (depending hospital availability

• Test Executive Function

  Completed on second PKAB/CFN imaging day (Between 3 to 6 weeks into alcohol cessation)

• Baseline Visual Processing Speed

  Up to 3 months prior to initial imaging or on initial imaging day (depending hospital availability

Study Arms (2)

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.

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.

Radiation: PKAB; Radiation: CFN

Interventions

Detoxification Program OTHER

Patients will begin inpatient or outpatient detoxification prior to completing imaging

Alcohol Use Disorder population completing Detoxification

PKAB RADIATION

90 PET Imaging Scan using \[11C\]LY2795050 (AKA \[11C\]PKAB)

Alcohol Use Disorder population completing Detoxification; Healthy Control population

CFN RADIATION

90 Pet Imaging Scan using \[11C\]-Carfentanil

Alcohol Use Disorder population completing Detoxification; Healthy Control population

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06519, United States

RECRUITING

MeSH Terms

Conditions

Alcoholism

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Kelly Cosgrove, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marc Grasso

CONTACT

2037375083; marc.grasso@yale.edu

Kelly Cosgrove, PhD

CONTACT

2037376969; kelly.cosgrove@yale.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Model Details: All subjects will be asked to complete both PKAB and CFN PET Imaging scans, AUD subset will participate in a detoxification program

Study Record Dates

• First Submitted: June 15, 2023
• First Posted: July 24, 2023
• Study Start: November 7, 2023
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: April 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)