Comparative Evaluation of Nicotine Analogs

NCT07585006 | Not Yet Recruiting Phase 1

• 2 other identifiers: OSU-25353NCI-2026-00343
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial compares electronic cigarette (EC) user preferences and smoking behaviors of nicotine analogs to nicotine to improve the understanding of nicotine analog addictiveness. Over the last ten years, EC use has become a major concern due to its increased use among adolescents and young adults. Though progress has been made in regulating nicotine containing products, some companies have shifted toward producing products containing nicotine analogs. ECs are battery-powered electronic devices designed to atomize a nicotine (the poisonous chemical found in tobacco)-containing liquid solution for inhalation in a manner that simulates smoking a tobacco cigarette. When nicotine enters the body, it causes an increased heart rate and use of oxygen by the heart, and a sense of well-being and relaxation. Nicotine analogs are compounds that are similar to nicotine in their chemical structure. Some nicotine analogs have been shown to have nicotine-like effects; however, more research is needed to prove they function similarly to nicotine and/or have similar effects. Comparing EC user preferences and smoking behaviors of nicotine analogs to nicotine may help improve the understanding of nicotine analog addictiveness.

Conditions

Tobacco-Related Carcinoma; Addiction

Outcome Measures

Primary Outcomes (3)

• Nicotine urges/craving (QSU)

  E-cigarette (EC) urges/craving will be measured with a modified version of the 10-item Tiffany-Drobes Questionnaire of Smoking Urges: Brief Form (QSU). Words such as "cigarette" and "smoke" are replaced with words such as "e-cigarette" and "vape." Each of the 10 items is scored on a 7 point Likert scale. Similar to previous studies, we will collapse the items into two previously identified factors (Factor 1: strong desire and intention to smoke; Factor 2: anticipation of relief from withdrawal symptoms). Scores are calculated by summing the items and range from 5 to 35 with higher scores indicating greater craving to smoke.

  Before puffing (0 minutes), and at 5, 15, 65, 95, and 125 minutes after the start of the puffing session; at Visit 1 (baseline), Visit 2 (≥ 48 hours after the previous visit), and Visit 3 (end-of-study visit; ≥ 48 hours after the previous visit)

• Nicotine withdrawal symptoms (MNWS)

  The 15-item version of the Minnesota Nicotine Withdrawal Scale (MNWS) will be used to measure nicotine withdrawal symptoms. Items are rated on a 5-point scale from 0 (none) to 4 (severe) where higher scores indicate a greater experience of withdrawal symptoms.

  Before puffing (0 minutes), and at 5, 15, 65, 95, and 125 minutes after the start of the puffing session; at Visit 1 (baseline), Visit 2 (≥ 48 hours after the previous visit), and Visit 3 (end-of-study visit; ≥ 48 hours after the previous visit)

• Economic demand indices (E-CPT)

  Consumer demand as measured by the E-Cigarette Purchase Task (E-CPT) will be used to measure economic demand. Participants will report the volume (mLs) or puffs of e-liquid they would be willing to purchase and use within 24 hours at a given price, which will incrementally increase from $0 to $1,120.

  After completion of the 60 minute ad lib puffing session; at Visit 1 (baseline), Visit 2 (≥ 48 hours after the previous visit), and Visit 3 (end-of-study visit; ≥ 48 hours after the previous visit)

Secondary Outcomes (7)

• Modified EC evaluation questionnaire (mCEQ)

  After completion of the 60 minute ad lib puffing session; at Visit 1 (baseline), Visit 2 (≥ 48 hours after the previous visit), and Visit 3 (end-of-study visit; ≥ 48 hours after the previous visit)

• Use topography: Inter-puff-interval

  60 minute puffing session; at Visit 1 (baseline), Visit 2 (≥ 48 hours after the previous visit), and Visit 3 (end-of-study visit; ≥ 48 hours after the previous visit)

• Use topography: Puffing duration

  60 minute puffing session; at Visit 1 (baseline), Visit 2 (≥ 48 hours after the previous visit), and Visit 3 (end-of-study visit; ≥ 48 hours after the previous visit)

• Use topography: Total puff volume

  60 minute puffing session; at Visit 1 (baseline), Visit 2 (≥ 48 hours after the previous visit), and Visit 3 (end-of-study visit; ≥ 48 hours after the previous visit)

• Nicotine/Nicotine analog pharmacokinetics: Cmax

  Immediately before puffing (0 minutes), and at 5, 15, 65, and 125 minutes after the start of the puffing session; at Visit 1 (baseline), Visit 2 (≥ 48 hours after the previous visit), and Visit 3 (end-of-study visit; ≥ 48 hours after the previous visit)

Study Arms (6)

Sequence 1 (nicotine, 6-MN, nicotinamide)

EXPERIMENTAL

VISIT 1: Participants take 1 puff of nicotine EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotine EC as much or as little as they like over 1 hour. VISIT 2: Participants take 1 puff of 6-MN EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use 6-MN EC as much or as little as they like over 1 hour. VISIT 3: Participants take 1 puff of nicotinamide EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotinamide EC as much or as little as they like over 1 hour. Additionally, patients undergo urine sample collection during screening and blood sample collection on study.

Procedure: Biospecimen Collection; Drug: Nicotine; Drug: 6-Methyl Nicotine; Drug: nicotinamide; Behavioral: Puffing Topography Research; Other: Survey Administration

Sequence 2 (nicotine, nicotinamide, 6-MN)

EXPERIMENTAL

VISIT 1: Participants take 1 puff of nicotine EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotine EC as much or as little as they like over 1 hour. VISIT 2: Participants take 1 puff of nicotinamide EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotinamide EC as much or as little as they like over 1 hour. VISIT 3: Participants take 1 puff of 6-MN EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use 6-MN EC as much or as little as they like over 1 hour. Additionally, patients undergo urine sample collection during screening and blood sample collection on study.

Procedure: Biospecimen Collection; Drug: Nicotine; Drug: 6-Methyl Nicotine; Drug: nicotinamide; Behavioral: Puffing Topography Research; Other: Survey Administration

Sequence 3 (nicotinamide, 6-MN, nicotine)

EXPERIMENTAL

VISIT 1: Participants take 1 puff of nicotinamide EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotinamide EC as much or as little as they like over 1 hour. VISIT 2: Participants take 1 puff of 6-MN EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use 6-MN EC as much or as little as they like over 1 hour. VISIT 3: Participants take 1 puff of nicotine EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotine EC as much or as little as they like over 1 hour. Additionally, patients undergo urine sample collection during screening and blood sample collection on study.

Procedure: Biospecimen Collection; Drug: Nicotine; Drug: 6-Methyl Nicotine; Drug: nicotinamide; Behavioral: Puffing Topography Research; Other: Survey Administration

Sequence 4 (nicotinamide, nicotine, 6-MN)

EXPERIMENTAL

VISIT 1: Participants take 1 puff of nicotinamide EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotinamide EC as much or as little as they like over 1 hour. VISIT 2: Participants take 1 puff of nicotine EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotine EC as much or as little as they like over 1 hour. VISIT 3: Participants take 1 puff of 6-MN EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use 6-MN EC as much or as little as they like over 1 hour. Additionally, patients undergo urine sample collection during screening and blood sample collection on study.

Procedure: Biospecimen Collection; Drug: Nicotine; Drug: 6-Methyl Nicotine; Drug: nicotinamide; Behavioral: Puffing Topography Research; Other: Survey Administration

Sequence 5 (6-MN, nicotine, nicotinamide)

EXPERIMENTAL

VISIT 1: Participants take 1 puff of 6-MN EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use 6-MN EC as much or as little as they like over 1 hour. VISIT 2: Participants take 1 puff of nicotine EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotine EC as much or as little as they like over 1 hour. VISIT 3: Participants take 1 puff of nicotinamide EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotinamide EC as much or as little as they like over 1 hour. Additionally, patients undergo urine sample collection during screening and blood sample collection on study.

Procedure: Biospecimen Collection; Drug: Nicotine; Drug: 6-Methyl Nicotine; Drug: nicotinamide; Behavioral: Puffing Topography Research; Other: Survey Administration

Sequence 6 (6-MN, nicotinamide, nicotine)

EXPERIMENTAL

VISIT 1: Participants take 1 puff of 6-MN EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use 6-MN EC as much or as little as they like over 1 hour. VISIT 2: Participants take 1 puff of nicotinamide EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotinamide EC as much or as little as they like over 1 hour. VISIT 3: Participants take 1 puff of nicotine EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotine EC as much or as little as they like over 1 hour. Additionally, patients undergo urine sample collection during screening and blood sample collection on study.

Procedure: Biospecimen Collection; Drug: Nicotine; Drug: 6-Methyl Nicotine; Drug: nicotinamide; Behavioral: Puffing Topography Research; Other: Survey Administration

Interventions

Biospecimen Collection PROCEDURE

Undergo urine and blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Sequence 1 (nicotine, 6-MN, nicotinamide); Sequence 2 (nicotine, nicotinamide, 6-MN); Sequence 3 (nicotinamide, 6-MN, nicotine); Sequence 4 (nicotinamide, nicotine, 6-MN); Sequence 5 (6-MN, nicotine, nicotinamide); Sequence 6 (6-MN, nicotinamide, nicotine)

Nicotine DRUG

Use nicotine EC

Also known as: (-)-Nicotine, NIC

Sequence 1 (nicotine, 6-MN, nicotinamide); Sequence 2 (nicotine, nicotinamide, 6-MN); Sequence 3 (nicotinamide, 6-MN, nicotine); Sequence 4 (nicotinamide, nicotine, 6-MN); Sequence 5 (6-MN, nicotine, nicotinamide); Sequence 6 (6-MN, nicotinamide, nicotine)

6-Methyl Nicotine DRUG

Use 6-MN EC

Also known as: 6-MN, Nixodine, Nixotine

Sequence 1 (nicotine, 6-MN, nicotinamide); Sequence 2 (nicotine, nicotinamide, 6-MN); Sequence 3 (nicotinamide, 6-MN, nicotine); Sequence 4 (nicotinamide, nicotine, 6-MN); Sequence 5 (6-MN, nicotine, nicotinamide); Sequence 6 (6-MN, nicotinamide, nicotine)

nicotinamide DRUG

Use nicotinamide EC

Also known as: NAM, Nixamide, Nixodine

Sequence 1 (nicotine, 6-MN, nicotinamide); Sequence 2 (nicotine, nicotinamide, 6-MN); Sequence 3 (nicotinamide, 6-MN, nicotine); Sequence 4 (nicotinamide, nicotine, 6-MN); Sequence 5 (6-MN, nicotine, nicotinamide); Sequence 6 (6-MN, nicotinamide, nicotine)

Puffing Topography Research BEHAVIORAL

Ancillary studies

Sequence 1 (nicotine, 6-MN, nicotinamide); Sequence 2 (nicotine, nicotinamide, 6-MN); Sequence 3 (nicotinamide, 6-MN, nicotine); Sequence 4 (nicotinamide, nicotine, 6-MN); Sequence 5 (6-MN, nicotine, nicotinamide); Sequence 6 (6-MN, nicotinamide, nicotine)

Survey Administration OTHER

Ancillary studies

Sequence 1 (nicotine, 6-MN, nicotinamide); Sequence 2 (nicotine, nicotinamide, 6-MN); Sequence 3 (nicotinamide, 6-MN, nicotine); Sequence 4 (nicotinamide, nicotine, 6-MN); Sequence 5 (6-MN, nicotine, nicotinamide); Sequence 6 (6-MN, nicotinamide, nicotine)

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 21 years or older
• Current adult EC user for at least the past 3 months (confirmed by cotinine testing strip)
• Willing and able to provide informed consent
• Willing to abstain from using any nicotine, tobacco, or marijuana products for 12 or more hours prior to the three lab visits
• Able to read, write, and speak English

You may not qualify if:

• Currently attempting to quit nicotine or tobacco products
• Use of other tobacco or nicotine products \> 10 days in the past month
• Have had a recent cardiac event or distress (defined as occurring within the previous 3 months)
• Have had a recent serious lung disease or infection (e.g., tuberculosis, cystic fibrosis, asthma, or lung cancer) (defined as occurring in the previous 30 days)
• Currently pregnant, planning to become pregnant, or breastfeeding (verified with urine pregnancy test)

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline
• Study pre-screener

MeSH Terms

Conditions

Behavior, Addictive

Interventions

Specimen Handling; Nicotine; Niacinamide

Condition Hierarchy (Ancestors)

Compulsive Behavior; Impulsive Behavior; Behavior

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Nicotinic Acids; Acids, Heterocyclic

Study Officials

• Theodore L Wagener, PhD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Data collectors, analysts, and participants will be blinded to the intervention sequence.
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 31, 2026
• First Posted: May 13, 2026
• Study Start: April 15, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 15, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)