I.V. Nicotine for Smoking Addiction

Overseen By Erin Schubert

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Pennsylvania

Must not be taking: Antipsychotics, Antidepressants, Stimulants, others

Disqualifiers: Pregnancy, Substance abuse, Hypertension, others

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

Compensation: Varies

Number of Visits: 3

13 Participants Needed

Trial Summary

What is the purpose of this trial?

Physically healthy adult smokers may be eligible for this study. Volunteers may participate in this study if they are 18 - 65 years old. Subjects will participate in two separate 7-hour PET/CT Scan Sessions (each with 2 hours of actual PET/CT scanning): one following an overnight abstinence and one following two overnights of abstinence. To achieve and confirm two overnights of abstinence, participants will present to the inpatient CHPS the day prior to the scheduled scan and stay overnight. The 2-\[18F\]-FA PET/CT brain scans will consist of an injection followed by an 7-hour infusion of 2-\[18F\]-FA. The scan session will begin at approximately 4 hours after the bolus injection. The PET/CT scan will occur in two segments. Starting at approximately 4 hours post bolus and infusion start, we will scan for approximately 90 minutes with a bolus injection of IV nicotine that will occur approximately 15 minutes into the scanning procedure. There will be a break in scanning of approximately 60 minutes, during which subjects will be allowed to get off the scanner and use the restroom, if necessary. The second scan segment will start at approximately 6.5 hours post bolus injection, t. This segment will last approximately 30 minutes. The pre and post nicotine images will be analyzed to evaluate for differences in receptor uptake after the nicotine "challenge". Subjects will have a structural Brain MRI performed within 1 year prior to study enrollment or subjects who have not had a Brain MRI that is deemed acceptable for use for this study will undergo a research Brain MRI after consent.

Will I have to stop taking my current medications?

Yes, you may need to stop taking certain medications. The trial excludes participants who are currently using or have recently stopped using specific medications like smoking cessation drugs, certain antidepressants, and heart medications. It's best to discuss your current medications with the study team to see if they affect your eligibility.

What data supports the effectiveness of the drug I.V. Nicotine for smoking addiction?

Research shows that nicotine, when administered intravenously, can produce effects similar to other drugs of abuse, such as increased heart rate and blood pressure, and feelings of euphoria. This suggests that I.V. Nicotine may have a role in addressing tobacco dependence by mimicking the psychoactive effects of smoking. ^{1 2 3 4 5}

Is I.V. Nicotine safe for humans?

The research articles provided do not contain specific safety data for I.V. Nicotine in humans. ^{1 5 6 7 8}

How does I.V. Nicotine differ from other smoking addiction treatments?

I.V. Nicotine is unique because it delivers nicotine directly into the bloodstream through an intravenous route, which may result in faster and more controlled nicotine delivery compared to traditional methods like patches or gum. This method could potentially offer a different mechanism of action by providing a more immediate effect, which might be beneficial for managing withdrawal symptoms. ^{1 2 5 9 10}

Eligibility Criteria

Adult smokers aged 18-65 who smoke at least 10 cigarettes a day for the past 6 months and have a carbon monoxide reading over 10 ppm. They must be willing to stay overnight in the hospital and abstain from smoking as required. Pregnant women, heavy alcohol drinkers, those with liver/kidney disease or high blood pressure, or users of certain medications are excluded.

Inclusion Criteria

I am between 18 and 65 years old.

Participants must be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study-specific procedures.

I have smoked at least 10 cigarettes a day for 6 months or more.

Exclusion Criteria

History within one year or currently receiving treatment for substance abuse other than nicotine (e.g., alcohol, opioids, cocaine, marijuana, or stimulants)

History of Posttraumatic Stress Disorder (PTSD), bipolar disorder, schizophrenia or other psychotic disorder or Attention-Deficit/Hyperactivity Disorder (ADHD) as assessed by medical record review and/or self-report. History of unipolar depression or anxiety disorder may be accepted; current depression or anxiety may be accepted if the severity does not require psychoactive medication as assessed by medical record review and/or self-report

History of head trauma, that in the opinion of an investigator may interfere with the uptake of [18F]2-FA, as assessed by medical record review and/or self-report

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

PET/CT Scan Sessions

Participants undergo two separate 7-hour PET/CT scan sessions, one following an overnight abstinence and one following two overnights of abstinence.

2 sessions, each 7 hours

2 visits (in-person)

Brain MRI

Participants will have a structural Brain MRI performed within 1 year prior to study enrollment or undergo a research Brain MRI after consent.

1 session

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• 2-[18F]-FA PET/CT
• I.V. Nicotine

Trial Overview The study tests how nicotine affects brain receptors in smokers using PET/CT scans after periods of abstinence. Participants will undergo two separate scan sessions with an injection and infusion of a tracer substance followed by IV nicotine during one session to compare receptor uptake before and after nicotine exposure.

Participant Groups

Group I: 2-[18F]-FA PET/CT Experimental Treatment 2 Interventions

Subjects will participate in two separate 10-hour PET/CT Scan Sessions (each with 2 hours of actual PET/CT scanning): one following an overnight abstinence and one following two overnights of abstinence. To achieve and confirm two overnights of abstinence, participants will present to the inpatient CHPS the day prior to the scheduled scan and stay overnight

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Findings from Research

In a study of 1,895 hospitalized smokers, 62% received nicotine replacement therapy (NRT) during their stay, and 42% of those surveyed reported using NRT within 2 weeks after discharge.

Smokers who used NRT while hospitalized were significantly more likely to continue using it after discharge, with adjusted rate ratios indicating a strong association between in-hospital NRT use and postdischarge initiation, suggesting that NRT can effectively support smoking cessation efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine replacement therapy use at home after use during a hospitalization. Regan, S., Reyen, M., Richards, AE., et al.[2021]

References

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

Imaging the neurochemistry of nicotine actions: studies with positron emission tomography. [2019]

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

Comparison of brain nicotine uptake from electronic cigarettes and combustible cigarettes. [2023]

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

Abuse liability and pharmacodynamic characteristics of intravenous and inhaled nicotine. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Nicotine replacement therapy use at home after use during a hospitalization. [2021]

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

Decreased Nicotinic Receptor Availability in Smokers with Slow Rates of Nicotine Metabolism. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

E-Cigarette Aerosol Deposition and Disposition of [11C]Nicotine Using Positron Emission Tomography: A Comparison of Nicotine Uptake in Lungs and Brain Using Two Different Nicotine Formulations. [2022]

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

123I-5-IA-85380 SPECT measurement of nicotinic acetylcholine receptors in human brain by the constant infusion paradigm: feasibility and reproducibility. [2016]

8. Germany pubmed.ncbi.nlm.nih.gov

Imaging Tobacco Smoking with PET and SPECT. [2015]

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

PET quantification of specific binding of carbon-11-nicotine in human brain. [2016]

10. Switzerland pubmed.ncbi.nlm.nih.gov

A vaccine for nicotine dependence: targeting the drug rather than the brain. [2017]