Imaging Mitochondrial Complex-I in Alcohol Use Disorder

Imaging Mitochondrial Complex-I With [F-18]BCPP-EF Positron Emission Tomography (PET) in Alcohol Use Disorder (AUD)

Studies proposed in this application will image mitochondrial Complex-I (MCI-I) and cerebral glucose metabolism (CGM) in alcohol use disorder (AUD) and matched healthy controls

Study Overview

• Status: Recruiting
• Conditions: Alcohol Use Disorder (AUD); Healthy Controls Group - Age and Sex-matched
• Intervention / Treatment: Drug: [F-18]BCPP-EF; Drug: [F-18]FDG

Detailed Description

This study uses [18F]BCPP-EF and [18F]FDG positron emission tomography (PET) to image mitochondrial complex I and cerebral glucose metabolism (CGM) in subjects with alcohol use disorder (AUD) and healthy controls (HC). Correlating PET outcome measures with relapse to alcohol in this study will clarify the mechanisms by which abnormal brain energetics modulate addictive behaviors.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Rajesh Narendran; Phone Number: 412-647-5176; Email: narendranr@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh
      • Contact: Principal Investigator; Phone Number: 412-647-5176; Email: narendranr@upmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Alcohol use disorders (AUD)

1. Males or females between 18 and 55 years old
2. fulfill DSM-5 criteria for alcohol use disorder
3. History of NIAAA heavy drinking (for males, routinely consuming more than 4 drinks on any day or more than 14 drinks per week; for females, routinely consuming more than 3 drinks on any day or more than 7 drinks per week) in the past 30 days
4. No other major DSM-5 psychiatric disorders including schizophrenia, schizoaffective disorder, bipolar disorder, developmental disorders, or current depressive disorders (unless they are related to alcohol intoxication, withdrawal, or an alcohol- induced mood disorder).
5. No other DSM-5 substance use disorders including opioids, cocaine, amphetamines, sedative-hypnotics, hallucinogens, and inhalants. Subjects with moderate and severe DSM-5 cannabis and tobacco use disorder will also be excluded;
6. Subjects not currently on psychotropic or medical medications that can influence binding to MC-I (e.g., metformin) or CGM (e.g., insulin, GLP-1 agonists), or increase the risks associated with an arterial line (e.g., warfarin, clopidogrel, aspirin, naproxen, ibuprofen, etc.).
7. No medical disorders that can influence the PET outcome measures (for example, MC-I binding is altered in Parkinson's disease, mild or major neurocognitive disorders, and mitochondrial disorders; CGM is altered in diabetes, severe hyperlipidemia, hypertension, obesity), increase the risks associated with blood sampling (anemia), or placement of an arterial line (history of deep vein thrombosis, pulmonary embolism, thrombocytopenia or thrombocytosis) for PET
8. Not currently pregnant or breast-feeding
9. Not currently employed as a radiation worker; or has participated in a radiation-related research protocol within the previous year such that the total cumulative annual radiation dose (i.e., from participation in the previous radioactive drug study [studies] and this study) would exceed the radiation dose limits specified in the FDA regulations (i.e., 21 CFR 361.1) that govern the research use of radiotracers
10. No medical or psychiatric contraindications to undergo an MRI scan (such as ferromagnetic tattoos/piercings, implants, medical equipment, history of gunshot, and claustrophobia).

Healthy controls (HC)

1. Males or females between 18 and 55 years old
2. No current or past DSM-5 psychiatric or substance use disorders other than tobacco use disorder
3. No history of heavy drinking as defined using NIAAA criteria in the past year
4. 5 to 10 above.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PET; Positron Emission Tomography Scans	Drug: [F-18]BCPP-EF; Radiotracer to measure binding to mitochondria complex -I; Drug: [F-18]FDG; Radiotracer to measure cerebral glucose metabolism

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dorsolateral prefrontal cortex [F-18]BCPP-EF VT	VT is the volume of distribution expressed relative to total plasma radioligand concentration, mL/cm3	Baseline scan (time 0)
Orbitofrontal cortex [F-18]BCPP-EF VT	VT is the volume of distribution expressed relative to total plasma radioligand concentration in mL/cm3	Baseline scan (time 0)
Medial Prefrontal Cortex [F-18]BCPP-EF VT	VT is the volume of distribution expressed relative to total plasma radioligand concentration, mL/cm3	Baseline scan (time 0)
Dorsolateral prefrontal cortex [F-18]FDG SUVR	SUVR is the standardized uptake value ratio with whole brain activity as a reference region, unitless	Baseline scan (time 0)
Orbitofrontal cortex [F-18]FDG SUVR	SUVR is the standardized uptake value ratio with whole brain activity as a reference region, unitless	Baseline scan (time 0)
Medial Prefrontal Cortex [F-18]FDG SUVR	SUVR is the standardized uptake value ratio with whole brain activity as a reference region, unitless	Baseline scan (time 0)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse to alcohol severity measure	Total number of ETG-negative urines (0 to 16)	during 8-week follow up
Penn Alcohol Craving Scale (PACS)	Mean weekly PACS scores (range 0 to 30; higher scores indicate more craving)	during 8-week follow up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Categorical relapse to alcohol	Abstained v Relapsed v Drop-out	8-week follow up
TIme to relapse	in weeks (0 to 8)	during 8 week follow up
Perceived Stress Scale (PSS)	Mean weekly PSS scores (0 to 40; higher scores indicate more stress)	during 8-week follow up
Prefrontal Cortical Thickness	MRI-derived cortical thickness measure derived using FreeSurfer, in mm	Baseline scan (time 0)

Collaborators and Investigators

• Sponsor: Rajesh Narendran
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Rajesh Narendran, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): December 31, 2032
• Study Completion (Estimated): December 31, 2032

Study Registration Dates

• First Submitted: September 11, 2026
• First Submitted That Met QC Criteria: September 11, 2026
• First Posted (Actual): September 17, 2026

Study Record Updates

• Last Update Posted (Actual): September 17, 2026
• Last Update Submitted That Met QC Criteria: September 11, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: PET; Alcohol use disorder; [F-18]FDG; [F-18]BCPP-EF
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Alcoholism
• Other Study ID Numbers: STUDY24030081; R01AA031453-01A1 (Other Grant/Funding Number: NIAAA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All individual participant data that underlie the results reported in the publication or upon study completion will be shared after de-identification via NIAAA Data Archive
• IPD Sharing Time Frame: Upon publication or study completion Data will be available as long as it is archived as per NIAAA Data Archive policy
• IPD Sharing Access Criteria: Aavailable as per NIAAA Data Archive policy
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No