[18F]NOS Imaging for Alcoholism

(AUD Trial)

Overseen By Jacob Dubroff, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Pennsylvania

Must not be taking: Narcotics, Antibiotics, Anti-inflammatories, Corticosteroids

Disqualifiers: HIV, Serious psychiatric illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

90 Participants Needed

Trial Summary

What is the purpose of this trial?

Study to enroll up to 90 individuals, those with an alcohol use disorder (AUD) (up to n=60) and non-dependent healthy volunteers (HV) (up to n=30). PET/CT imaging will be used to evaluate brain and whole-body inflammation using the investigational radiotracer \[18F\]NOS. All participants will have one \[18F\]NOS positron emission tomography/ computed tomography (PET/CT) scan performed.

Will I have to stop taking my current medications?

The trial requires participants to refrain from using certain medications, like narcotic pain relievers, antibiotics, and anti-inflammatory drugs, within 24 hours of MRI and PET procedures. If you're taking these types of medications, you may need to stop them temporarily for the study.

How does the drug [18F]NOS differ from other treatments for alcoholism?

[18F]NOS is unique because it targets the neuronal nitric oxide synthase (nNOS) system, which is involved in regulating alcohol consumption and its neurobehavioral effects. Unlike other treatments, it may specifically influence the brain's nitric oxide pathways, potentially reducing alcohol intake and preference by modulating the rewarding effects of alcohol. ^{1 2 3 4 5}

Research Team

Jacob Dubroff, MD, PhD

Principal Investigator

Perelman School of Medicine, Dept. of Radiology

Eligibility Criteria

This trial is for individuals aged 18 to 65 with alcohol use disorder (AUD) and healthy volunteers, willing to consent and complete study procedures. Excluded are those using certain medications, pregnant or breastfeeding women, people with untreated substance disorders (except nicotine/cannabis), HIV positive individuals, those with serious psychiatric illnesses or conditions that could affect the study's safety or results.

Inclusion Criteria

Willingness to provide signed informed consent and commit to completing the procedures in the study

I am between 18 and 65 years old.

Exclusion Criteria

Any current or past medical condition, illness, or disorder as assessed by medical record review and/or self-reported that is considered by a physician investigator to be a condition that could compromise participant safety or successful participation in the study

I am currently using corticosteroids or anti-inflammatory medications.

Positive urine drug screen for opiates, methamphetamine or cocaine at screening or study visit (may be repeated once and if result is negative on repeat it is not exclusionary)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo a PET/CT scan to evaluate brain and whole-body inflammation using the investigational radiotracer [18F]NOS

1 day

1 visit (in-person)

Companion Treatment Study

AUD participants enrolled in a companion treatment study undergo a second PET/CT scan and brain MRI after initiation of treatment

3-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after imaging and treatment

4 weeks

Treatment Details

Interventions

• [18F]NOS

Trial Overview [18F]NOS PET/CT scans are being tested to measure brain and whole-body inflammation in up to 90 participants—60 with AUD and 30 healthy volunteers. Each participant will undergo one [18F]NOS PET/CT scan during the study.

Participant Groups

Group I: HV-Healthy Volunteer Experimental Treatment 1 Intervention

30 adult men and women between the ages of 18-65 who do not have alcohol use disorder and are a healthy volunteer will be enrolled in this study.

Group II: AUD-Alcohol Use Disorder Experimental Treatment 1 Intervention

60 adult men and women who have alcohol use disorder will undergo up to 2 PET/CT scans each approximately 60 minutes of dynamic scanning starting at the time of injection of \[18F\]NOS. PET/CT imaging sessions will include an injection of ≤ 6.5 mCi (approximate range for most studies is anticipated to be 3.5-6.5 mCi) of \[18F\]NOS.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Findings from Research

Chronic alcohol exposure significantly increased the activity of neuronal nitric oxide synthase (nNOS) in the frontal cortex and striatum of rats, as indicated by higher Km and Vmax values.

The activity of nNOS in the cerebellum and hippocampus remained unchanged after chronic alcoholization, suggesting that the effects of alcohol on nNOS are region-specific in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulation of rat neuronal nitric oxide synthase activity by chronic alcoholization. Naassila, M., Beauge, F., Daoust, M.[2019]

In a rat model of binge ethanol intoxication, the use of nitric oxide synthase (NOS) inhibitors did not reduce neuronal damage, suggesting that endogenous nitric oxide may actually play a protective role against ethanol-induced neurotoxicity.

The study found that neuronal degeneration in certain brain regions was either unchanged or increased with NOS inhibitors, indicating that nitric oxide is not a neurotoxic mediator of ethanol's effects, but may instead help protect neurons from damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Binge ethanol-induced brain damage in rats: effect of inhibitors of nitric oxide synthase. Zou, JY., Martinez, DB., Neafsey, EJ., et al.[2019]

The nNOS inhibitor 7-nitroindazole (7-NI) effectively blocked the long-lasting locomotor sensitization and conditioned place preference (CPP) induced by ethanol in DBA/2J mice, suggesting its potential as a therapeutic target for alcohol-related behaviors.

The study demonstrated that 7-NI did not produce any rewarding or aversive effects on its own, indicating that its ability to attenuate ethanol's effects is specific and highlights the role of the nNOS system in the rewarding effects of drugs of abuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blockade of alcohol-induced locomotor sensitization and conditioned place preference in DBA mice by 7-nitroindazole. Itzhak, Y., Martin, JL.[2019]

Targeting neuronal nitric oxide synthase (nNOS) with antisense oligodeoxynucleotides in ethanol-dependent rats significantly reduced both ethanol intake and preference by 25-30%, indicating its specific role in alcohol consumption regulation.

The study also found that the anticraving drug acamprosate was effective in reducing ethanol intake by 58%, suggesting that both nNOS inhibition and acamprosate can be potential strategies for managing alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracerebroventricular injection of antisense oligos to nNOS decreases rat ethanol intake. Naassila, M., Beaugé, FJ., Sébire, N., et al.[2019]

Mice lacking the nNOS gene consumed significantly more alcohol from high-concentration solutions compared to wild-type mice, indicating that nNOS plays a crucial role in regulating alcohol drinking behavior.

nNOS-deficient mice showed reduced sensitivity to the sedative effects of ethanol and did not develop rapid tolerance to ethanol-induced hypothermia, suggesting that nNOS is important for the neurobehavioral effects of alcohol.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The neuronal nitric oxide synthase gene is critically involved in neurobehavioral effects of alcohol. Spanagel, R., Siegmund, S., Cowen, M., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Regulation of rat neuronal nitric oxide synthase activity by chronic alcoholization. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Binge ethanol-induced brain damage in rats: effect of inhibitors of nitric oxide synthase. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Blockade of alcohol-induced locomotor sensitization and conditioned place preference in DBA mice by 7-nitroindazole. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Intracerebroventricular injection of antisense oligos to nNOS decreases rat ethanol intake. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

The neuronal nitric oxide synthase gene is critically involved in neurobehavioral effects of alcohol. [2019]