[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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the connection between inflammation in the brain and body and alcohol use disorder (AUD) using a PET/CT scan with the radiotracer [18F]NOS. Participants with AUD will undergo up to two scans, while healthy volunteers without AUD will receive one scan. Suitable candidates include those who have been drinking heavily for at least a year, consuming at least 15 drinks a week, or those who drink less than 15 drinks a month and do not have AUD. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to contribute to groundbreaking insights.

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.

What prior data suggests that [18F]NOS is safe for PET/CT imaging?

Research has shown that the investigational radiotracer \[18F\]NOS is under study to assess its safety and efficacy. Some early studies have examined how well people tolerate \[18F\]NOS, focusing primarily on safety rather than effectiveness.

Currently, detailed information on specific side effects or reactions is unavailable. As this is an early-stage trial, researchers closely monitor the treatment to ensure its safety for further testing. Early trials aim to identify any safety issues before progressing to larger studies, focusing on ensuring \[18F\]NOS is safe and well-tolerated by participants.

Participants in the trial will undergo a PET/CT scan using \[18F\]NOS to measure inflammation in the brain and body. This helps researchers understand how the treatment interacts with the human body. Prospective participants should discuss any safety concerns or questions with the research team. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about [18F]NOS imaging for alcoholism because it offers a novel way to understand the brain's involvement in alcohol use disorder. Unlike current treatments, which typically focus on reducing alcohol consumption through behavioral therapy or medications like naltrexone and acamprosate, [18F]NOS provides a new imaging technique. This method uses a radiolabeled tracer to visualize nitric oxide synthase in the brain, potentially revealing insights into the neurological processes of alcoholism. By targeting nitric oxide pathways, this imaging approach could lead to more precise and effective treatment strategies in the future.

What evidence suggests that [18F]NOS imaging is effective for evaluating inflammation in alcohol use disorder?

Research has shown that [18F]NOS is used in PET/CT scans to detect inflammation in the brain and body. This trial will involve two groups: healthy volunteers and participants with alcohol use disorder (AUD). [18F]NOS identifies areas where the enzyme iNOS is active, often found in inflamed body parts. Although [18F]NOS does not treat AUD, its ability to highlight inflammation could help researchers better understand and address the condition. This understanding might lead to improved treatments in the future. ^{2 3 6 7 8}

Who Is on the Research Team?

Jacob Dubroff, MD, PhD

Principal Investigator

Perelman School of Medicine, Dept. of Radiology

Are You a Good Fit for This Trial?

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05885594?term=AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(AREA%5BInterventionSearch%5D(PROPYL%20ALCOHOL)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)))))&rank=10

Imaging Inflammation With Alcohol Use Disorder: an [18F] ... 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).

2. withpower.com withpower.com/trial/18fnos-imaging-for-alcoholism-68d5c

[18F]NOS Imaging for Alcoholism (AUD Trial) This trial is for individuals aged 18 to 65 with alcohol use disorder (AUD) and healthy volunteers, willing to consent and complete study ...

3. trialx.com trialx.com/clinical-trials/listings/233853/imaging-inflammation-with-alcohol-use-disorder-an-18fnos-study/

Imaging Inflammation With Alcohol Use Disorder: an [18F] ... PET/CT imaging will be used to evaluate brain and whole-body inflammation using the investigational radiotracer [18F]NOS.

4. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK23142/

[18F]6-(2-Fluoropropyl)-4-methyl-pyridin-2-amine - NCBI - NIH iNOS is induced by various inflammatory stimuli in activated macrophages and other types of cells and plays an important role in immunity and ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-04886

Fluorine F 18 Nitric Oxide Synthase PET/CT for the ... [18F]NOS is an experimental radioactive molecule used in PET imaging to measure inflammation in various organs in the body, including the brain. This study may ...

6. trialstoday.org trialstoday.org/trial/NCT05885594

Imaging Inflammation With Alcohol Use Disorder [18F]-6-(2-fluoro-propyl)-4-methylpyridin-2-amine, also known as ... Data will be collected to evaluate uptake of [18F]NOS in the brain ...

7. mdpi.com mdpi.com/2073-4409/11/19/3081

[18F]NOS PET Brain Imaging Suggests Elevated ... We conducted a human pilot study to evaluate the feasibility of targeting the inducible isoform of nitric oxide synthase using the [18F]NOS ...

8. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT03968042/

Trial | NCT03968042 Alcohol is one of most common harmful substance, and alcohol intake brings great burden on health worldwide. Excess alcohol intake may lead to ...