Comparative Pharmacokinetics and Pharmacodynamics of Synthetic Nicotine

Sponsor

University of California, San Francisco (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05962229

Collaborator

National Institute on Drug Abuse (NIDA) (NIH)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In a crossover study, experienced electronic cigarette users will vape 3 different forms of nicotine: natural (derived from tobacco), synthetic, or a 50:50 mixture of both natural and synthetic. The investigators will compare nicotine metabolism, cardiovascular effects, patterns of self-administration, and participants' feelings of craving/withdrawal and enjoyment.

Condition or Disease	Intervention/Treatment	Phase
Nicotine Dependence Nicotine Vaping	Drug: (S)-Nicotine Drug: (R)- nicotine Drug: Racemic nicotine	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

18 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Within-subject, single-blinded crossover study. Participants will be randomized to the order of the 3 conditions using a Latin Square design.Within-subject, single-blinded crossover study. Participants will be randomized to the order of the 3 conditions using a Latin Square design.

Masking:

Single (Participant)

Primary Purpose:

Basic Science

Official Title:

Comparative Pharmacokinetics and Pharmacodynamics of Synthetic Nicotine

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Sep 1, 2025

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: S-nicotine (tobacco) as the starting condition Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (S)-nicotine.	Drug: (S)-Nicotine Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 100% (S)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes. Drug: (R)- nicotine Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 100% (R)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes. Drug: Racemic nicotine Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 50% (R)-nicotine and 50% (S)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes. Other Names: 50:50 mixture of (S)- and (R)-nicotine
Experimental: R-nicotine (synthetic) as the starting condition Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (R)-nicotine.	Drug: (S)-Nicotine Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 100% (S)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes. Drug: (R)- nicotine Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 100% (R)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes. Drug: Racemic nicotine Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 50% (R)-nicotine and 50% (S)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes. Other Names: 50:50 mixture of (S)- and (R)-nicotine
Experimental: Racemic (50:50 S- and R- nicotine) as the starting condition Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 50% (S)-nicotine and 50% (R)-nicotine.	Drug: (S)-Nicotine Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 100% (S)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes. Drug: (R)- nicotine Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 100% (R)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes. Drug: Racemic nicotine Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 50% (R)-nicotine and 50% (S)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes. Other Names: 50:50 mixture of (S)- and (R)-nicotine

Arm

Intervention/Treatment

Experimental: S-nicotine (tobacco) as the starting condition

Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (S)-nicotine.

Drug: (S)-Nicotine

Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 100% (S)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes.

Drug: (R)- nicotine

Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 100% (R)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes.

Drug: Racemic nicotine

Participants will spend 8 hours in the hospital research ward and will vape e-liquid containing 50% (R)-nicotine and 50% (S)-nicotine. They will vape following a standardized session, followed by a 4 hour abstinence period. Participants will then vape as they wish (ad libitum) for 90 minutes.

Other Names:

50:50 mixture of (S)- and (R)-nicotine

Experimental: R-nicotine (synthetic) as the starting condition

Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 100% (R)-nicotine.

Drug: (S)-Nicotine

Drug: (R)- nicotine

Drug: Racemic nicotine

Other Names:

50:50 mixture of (S)- and (R)-nicotine

Experimental: Racemic (50:50 S- and R- nicotine) as the starting condition

Participants will spend 8 hours in the hospital research ward where they will vape e-liquid containing 50% (S)-nicotine and 50% (R)-nicotine.

Drug: (S)-Nicotine

Drug: (R)- nicotine

Drug: Racemic nicotine

Other Names:

50:50 mixture of (S)- and (R)-nicotine

Outcome Measures

Primary Outcome Measures

Mean Nicotine Exposure Over Time [Up to 7 hours]
Plasma nicotine area under the concentrated time curve (AUC) (ng/ml*h)

Secondary Outcome Measures

Mean Amount of Nicotine Consumed Over Time [120 minutes]
Nicotine self-administration determined by device weight change before and after use multiplied by the nicotine concentration in the e-liquid

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy on the basis of medical history and limited physical examination.
Current regular user of E-Cigarettes (≥ 15 days in the past 30 days)

Exclusion Criteria:

• Medications
Use of medications that are inducers of nicotine metabolizing enzyme CYP2A6 (Example: rifampicin, carbamazepine, phenobarbital, and other anticonvulsant drugs).
Use of sympatholytic medications for cardiovascular conditions including hypertension (Example: beta and alpha-blockers).
Concurrent use of nicotine-containing medications (Example: nicotine patch, lozenge, gum).
Any stimulant medications (example: Adderall) generally given for ADHD treatment.

• Pregnancy

Pregnancy (self-reported and urine pregnancy test)
Breastfeeding (determined by self-report)
Women of childbearing potential must be using an acceptable method of contraception
Inability to read and write in English
A known propylene glycol/vegetable glycerin allergy
Uncomfortable with getting blood drawn

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Zuckerberg San Francisco General Hospital (ZSFG)	San Francisco	California	United States	94110

Sponsors and Collaborators

University of California, San Francisco
National Institute on Drug Abuse (NIDA)

Investigators

Principal Investigator: Neal Benowitz, MD, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University of California, San Francisco

ClinicalTrials.gov Identifier:

NCT05962229

Other Study ID Numbers:

22-36348
1R01DA057282-01

First Posted:

Jul 27, 2023

Last Update Posted:

Jul 27, 2023

Last Verified:

Jul 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by University of California, San Francisco

Nicotine Pharmacokinetics

Nicotine Pharmacodynamics

Vaping

E-cigarettes

Additional relevant MeSH terms:

Tobacco Use Disorder

Nicotine

Study Results

No Results Posted as of Jul 27, 2023