An Early Phase 1 interventional study of Baseline [C-11]NOP-1A PET scan and Hydrocortisone in Alcohol Use Disorder, sponsored by Rajesh Narendran. Recruiting at 1 site in United States. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-06-03.
Sponsored by Rajesh Narendran · Early Phase 1, Interventional, and Basic science
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.
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.
Heavy drinking alcohol use disorder subjects (AUD)
Healthy Control subjects (HC)
\[C-11\]NOP-1A
Radiation: Baseline [C-11]NOP-1A PET scan · Drug: Hydrocortisone · Radiation: Post-hydrocortisone [C-11]NOP-1A PET scan
Radiotracer
Intravenous, 1 mg/Kg
Radiotracer
Amygdala DELTA VT
VT is the volume of distribution expressed relative to total plasma radioligand concentration; DELTA VT is the change from baseline to post-hydrocortisone
Time frame: Baseline/pre hydrocortisone, and 3-hours post hydrocortisone
Total number of negative ETG tests
Represents level of abstinence in contingency management
Time frame: over 8-week follow-up
Midbrain DELTA VT
VT is the volume of distribution expressed relative to total plasma radioligand
Time frame: Baseline/pre hydrocortisone and 3-hours post hydrocortisone
Ventral striatum DELTA VT
VT is the volume of distribution expressed relative to total plasma radioligand
Time frame: Baseline/pre hydrocortisone and 3-hours post hydrocortisone
Orbitofrontal Cortex DELTA VT
VT is the volume of distribution expressed relative to total plasma radioligand
Time frame: Baseline/pre hydrocortisone and 3-hours post hydrocortisone
Relapse to alcohol
Abstained; Relapsed; Drop-out
Time frame: over 8-weeks follow up
Relapse to alcohol severity (self-reported)
Heavy drinking days/week and Abstinent days/week
Time frame: over 8- week follow up
Perceived Stress Scale
mean and peak scores during follow-up
Time frame: over 8-week follow up
Penn Alcohol Craving Scale
mean and peak score during follow up
Time frame: over 8-week follow up
Plasma cortisol
Plasma cortisol measured in blood
Time frame: Baseline/pre hydrocortisone and post-hydrocortisone
Plan to share: Yes — All individual participant data that underlie the results reported in the publication or upon study completion will be shared after de-identification via the NIAAA Data Archive
Supporting information: Study protocol
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Rajesh Narendran