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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an intravenous (IV) nicotine treatment to observe its effects on smokers' brain activity after periods of abstinence. Researchers aim to understand how the brain's receptors respond to nicotine after smokers abstain for one or two nights. The study uses brain scans and nicotine injections to monitor these changes. Smokers who have been smoking at least 10 cigarettes a day for six months and are willing to stay overnight for the study may qualify. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants a unique opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that nicotine, when administered intravenously, is usually well-tolerated. However, nicotine's addictive nature can lead to dependency if not carefully managed, despite the body's ability to handle it well in controlled settings.

Specific safety data on intravenous nicotine remains limited, as this trial is in its early stages. Researchers are closely examining its safety. Early-phase trials primarily focus on ensuring a treatment's safety for participants, so researchers are carefully monitoring any potential side effects or risks.

The PET/CT scan used with the nicotine infusion is a common imaging method in medical studies and is generally considered safe. These scans help researchers observe how nicotine affects brain activity.

In summary, while nicotine is known to be addictive, the controlled environment and careful monitoring in this trial aim to reduce risks and ensure participant safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for smoking addiction involve nicotine replacement therapies, such as patches or gum, or medications like varenicline and bupropion that help reduce cravings. However, intravenous (I.V.) nicotine offers a different approach by delivering nicotine directly into the bloodstream, potentially providing more immediate relief from withdrawal symptoms. This method could help researchers better understand the brain’s response to nicotine and improve the precision of nicotine dosage, leading to more effective treatments. Researchers are excited about this trial because it could uncover new insights into nicotine addiction and pave the way for innovative therapies.

What evidence suggests that this trial's treatments could be effective for smoking addiction?

Studies have shown that nicotine replacement therapies (NRTs) can help people quit smoking. For example, using nicotine in various forms can increase quit rates from 10% to 17%. Research suggests that combining different NRTs might be more effective than using just one type. Although limited data exists on using I.V. nicotine specifically, this trial will explore its potential to provide nicotine to the body and ease withdrawal symptoms. Early signs indicate this approach might reduce the number of cigarettes smoked, potentially aiding in quitting smoking. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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

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.

I agree to follow all study rules, not smoke, and stay overnight at the hospital if needed.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK537066/

Nicotine Addiction and Smoking: Health Effects and ... - NCBI Rates of smoking cessation may increase from 10% in control groups to 17% in persons using any form of NRT, and using 2 types of NRT is more effective than ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2211335525001056

The relationship between nicotine dependence and ... A high level of nicotine dependence was recorded for 38 participants (13 %). No significant differences were reported in the participants' characteristics ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2981675/

Increased Self-efficacy to Quit and Perceived Control over ... The results highlight two relatively under-studied potential psychological predictors of abstinence following treatment for nicotine dependence.

4. nejm.org nejm.org/doi/full/10.1056/NEJMcp2032393

Tobacco Addiction The duration of therapy is usually 8 to 12 weeks; even though most smokers who have a response to nicotine-replacement therapy will quit smoking ...

5. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2829810

Integrated Nicotine Replacement and Behavioral Support ... Main Outcomes and Measures The primary outcome was at least a 50% reduction in the number of cigarettes smoked, self-reported as cigarette use ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK568714/

Nicotine Addiction and Smoking: Health Effects and ... - NCBI The effect of cigarette smoking, alcohol consumption and fruit and vegetable consumption on IVF outcomes: a review and presentation of original data. Reprod ...

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2806505

Nicotine Dependence Among Adults With Cigarette Use in ... We found that nicotine dependence prevalence decreased from 59.52% in 2006 to 56.00% in 2019 (difference, 3.52 percentage points; percentage ...