Reducing Tobacco-associated Lung Cancer Risk: A Randomized Clinical Trial of AB-free Kava

NCT05081882 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: KavaOCR40933IRB202101885
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

Tobacco use is the leading cause of many preventable diseases, particularly lung cancer. Based on the national cancer data in 2020, Florida has the highest lung cancer incidence (18,150 cases) with the most deaths (10,580 deaths) among all the states in the United States. Unfortunately, around 16% of adults in Florida continue to smoke cigarettes due to its addictive nature and the limited success of current cessation strategies. Therefore, there is an unmet and urgent need for novel interventions to improve the success of tobacco cessation. If such an intervention can reduce tobacco-associated lung carcinogenesis, that will be more desirable. The ultimate goal of this study is to develop a safe and effective kava-based intervention to enable tobacco cessation and reduce lung cancer risk, which will improve the health of Floridians. This study will evaluate the compliance with a daily kava regimen among active smokers who have no intention to quit smoking. This study will also investigate whether kava use can reduce tobacco use and dependence, as well as tobacco-associated lung carcinogenesis.

Conditions

Smoking

Keywords

tobacco dependence; smoking cessation; kava

Outcome Measures

Primary Outcomes (1)

• Urinary Total Nicotine Equivalents

  Measure urinary total nicotine equivalents (TNE). TNE is the sum of nicotine and its metabolites in a participant's urine. TNE was measured at baseline (on Day 1 of treatment), after 1 and 2 weeks on treatment, at the end of treatment, at 4 weeks after end of treatment and at 8 weeks after end of treatment.

  at baseline (on Day 1 of treatment), after 1 and 2 weeks on treatment, at the end of treatment, at 4 weeks after end of treatment and at 8 weeks after end of treatment.

Secondary Outcomes (8)

• Reinforcing Effects of Smoking

  At baseline (Day 1 of treatment), at 1 week and 2 weeks after beginning treatment, and at the end of treatment (28 days after starting treatment)

• Participant Reported Number of Cigarettes Smoked Weekly

  At baseline (day 1) of treatment, at 1 week and 2 weeks after beginning treatment, and at the end of treatment (28 days after beginning treatment)

• Participant Urge to Smoke

  At baseline (day 1 of treatment), at 1 week and 2 weeks after beginning treatment, and at the end of treatment (28 days after beginning treatment)

• Nicotine Dependency

  At baseline (day 1 of treatment), at 1 week and 2 weeks after beginning treatment, and at the end of treatment (28 days after beginning treatment)

• Perceived Stress

  At baseline (day 1 of treatment), at 1 week and 2 weeks after beginning treatment, and at the end of treatment (28 days after beginning treatment)

Study Arms (2)

Kava Intervention

EXPERIMENTAL

Drug: Kava

Placebo Control

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Kava DRUG

Participants on this arm will take one kava capsule (each capsule contains 75 mg of kavalactones) orally three times daily for 28 days.

Kava Intervention

Placebo DRUG

Participants on this arm will take one placebo capsule orally three times daily for 28 days.

Placebo Control

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• adults aged 21 years or above
• self-reported smoking at least 5 cigarettes/day for the past year with no intention to quit at time of screening visit
• expired carbon monoxide level of more than 8 ppm at recruitment
• willingness to participate in the proposed study, as indicated by signed informed consent
• access to a functional telephone
• expected presence in the study's geographical area for the next 4 months
• not currently enrolled in any smoking cessation programs per self-report
• female subjects of childbearing potential will be required to practice acceptable methods of birth control (the acceptable methods of birth control include birth control pills, Birth Control Shot, Birth Control Implant, Intrauterine Device \[IUD\], Diaphragm, and cervical cap)

You may not qualify if:

• history of active cancer (other than non-melanoma skin cancer) within the past 2 years
• diagnosed with liver dysfunction or with previous liver diseases
• levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, or total bilirubin over limit of normal range at prescreen
• inability to refrain from acetaminophen, alcohol (no more than one drink daily via self-report)
• are pregnant or nursing (lactating) or of childbearing age planning to become pregnant or unwilling to use adequate contraception during the study
• participant answered "Yes" to any of the ASQ questions 1 through 3, or refuses to answer all of the questions. If subject answers 'Yes' to question 4 but the most recent suicide attempt took place more than12 months from screening visit then subject is still eligible.

Sponsors & Collaborators

• University of Florida: lead
• Florida Department of Health: collaborator

Study Sites (1)

University of Florida

Gainesville, Florida, 32608, United States

Location

Related Publications (2)

• Freeman B, Bian T, Xu G, Wheeler M, Fujioka N, Malaty J, Orlando FA, Braithwaite D, Salloum RG, Bruijnzeel AW, Zhang W, Xing C. Assessing the physiological relevance of the bioactivation of tobacco-specific carcinogen NNK and its metabolite NNAL: quantitative analyses of hydrolysis products from their protein adducts under different carcinogen exposure conditions. Carcinogenesis. 2026 Apr 9;47(2):bgag031. doi: 10.1093/carcin/bgag031.

  PMID: 42142878 DERIVED

• Xing C, Malaty J, Malham MB, Nehme AMA, Freeman B, Huo Z, Firpi-Morrel R, Salloum RG. Reducing tobacco-associated lung cancer risk: a study protocol for a randomized clinical trial of AB-free kava. Trials. 2023 Jan 18;24(1):36. doi: 10.1186/s13063-023-07081-x.

  PMID: 36653872 DERIVED

MeSH Terms

Conditions

Smoking; Tobacco Use Disorder; Smoking Cessation

Condition Hierarchy (Ancestors)

Behavior; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Health Behavior

Results Point of Contact

• Title: Allison Allegra
• Organization: University of Florida

allisonallegra3@ufl.edu

352-294-5691

Study Officials

• Ramzi Salloum, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2021
• First Posted: October 18, 2021
• Study Start: June 9, 2022
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: September 3, 2026
• Results First Posted: September 3, 2026

Record last verified: 2026-08

Locations

US (1)