Imaging CRF X NOP Interactions in Alcohol Use Disorder

Purpose

This positron emission tomography imaging study uses [C-11]NOP-1A and hydrocortisone to image stress-modulating proteins in heavy drinking alcohol use disorder (AUD) subjects and healthy controls (HC). It will also characterize the role of these stress-regulating proteins in a relapse to alcohol.

Condition

  • Alcohol Use Disorder

Eligibility

Eligible Ages
Between 18 Years and 55 Years
Eligible Sex
All
Accepts Healthy Volunteers
Yes

Criteria

Heavy drinking alcohol use disorder subjects (AUD)

1. Males or females between 18 and 55 years old

2. fulfill DSM-5 criteria for moderate or severe ( > or = 4 criteria) alcohol use
disorder

3. fulfill both NIAAA heavy drinking91 (consuming for males > or = 5 drinks on any day;
for females > or = 4 drinks on any day) and WHO high-risk/very high-risk drinking
level criteria66 (for males > or = 30 drinks/week; for females > or = 20
drinks/week) in the past four weeks prior to enrollment

4. No lifetime DSM-5 psychiatric disorders, including schizophrenia, schizoaffective
disorder, bipolar disorder, or developmental disorders.

5. No comorbid current DSM-5 depressive or anxiety disorders

6. No other current DSM-5 substance use disorders, including opioids, cocaine,
amphetamines, sedative-hypnotics, hallucinogens, and inhalants. Subjects with
current moderate and severe DSM-5 cannabis use disorder will also be excluded

7. Not currently on psychotropic medications that can directly (e.g., buprenorphine) or
indirectly influence binding to NOP (e.g., medications that alter dopamine, GABA,
glutamate, etc.) or modify alcohol consumption patterns (e.g., naltrexone,
acamprosate, disulfiram);

8. No regular use of medical medications that can potentially interact with
hydrocortisone (other corticosteroids, mifepristone, etc.) or increase the risks
associated with arterial line removal (warfarin, clopidogrel, aspirin, naproxen,
ibuprofen, etc.)

9. No clinically significant medical or neurological illnesses, including a history of
immune compromise, HPA-axis dysfunction, Cushing's syndrome, glaucoma, morbid
obesity, severe hyperglycemia, and hyperlipidemia, all of which are
contraindications for hydrocortisone

10. No history of anemia or history of deep vein thrombosis, pulmonary embolism,
thrombocytopenia or thrombocytosis

11. Not currently pregnant or breast-feeding

12. No history of complicated alcohol withdrawal symptoms such as seizures, alcoholic
hallucinosis, delirium tremens, or required admission to an inpatient detox program
to prevent such symptoms

13. 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 previous radioactive
drug 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

14. No metallic objects in the body that are contraindicated for MRI.

Healthy Control subjects (HC)

1. Males or females between 18 and 55 years old

2. No DSM-5 psychiatric or substance use disorders other than tobacco use disorder

3. No NIAAA heavy drinking in the past year (> or = 5 drinks on any day or more than 14
drinks per week for males; > or = 4 drinks on any day or more than 7 drinks per week
for females)

4. 7 to 14 above.

Study Design

Phase
Early Phase 1
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Intervention Model Description
Alcohol use disorder and controls will receive the same intervention
Primary Purpose
Basic Science
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
PET
[C-11]NOP-1A
  • Radiation: Baseline [C-11]NOP-1A PET scan
    Radiotracer
  • Drug: Hydrocortisone
    Intravenous, 1 mg/Kg
  • Radiation: Post-hydrocortisone [C-11]NOP-1A PET scan
    Radiotracer

Recruiting Locations

University of Pittsburgh
Pittsburgh, Pennsylvania 15213

More Details

Status
Recruiting
Sponsor
Rajesh Narendran

Study Contact

Rajesh Narendran
412-647-5176
narendranr@upmc.edu

Detailed Description

Hydrocortisone administration leads to a 10 to 15% increase in [11C]NOP-1A VT in brain regions, including the amygdala. Increased NOP measured in response to cortisol, and by extension, corticotrophin-releasing factor (CRF), in this paradigm reflects an individual's ability to enhance N/OFQ transmission during stress. Here, the investigators propose to use this novel imaging paradigm to compare hydrocortisone-induced increases in [11C]NOP-1A binding (DVT) in the amygdala (and secondary reward regions) in heavy drinking AUD subjects Vs. HC. The hypothesis that hydrocortisone-induced increases in [11C]NOP-1A binding (DVT) will be larger in heavy drinking AUD relative to HC (aim 1), and this will predict relapse to alcohol (aim 2). Such a result will support the presence of a hyperactive NOP receptor system in response to increases in cortisol/CRF during conditions such as stress, chronic pain, etc., promoting relapse in heavy drinking AUD subjects.