Exploring the Impact of Two-week Kava on the Metabolism of Nicotine and NNK

NCT03606655 | Withdrawn Phase 1 DMC FDA Drug

• 3 other identifiers: IRB201801361UF-PDO-HN-1001OCR18359
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Tobacco smoking is the leading cause of head and neck cancer in the United States. Smoking cessation remains a challenge for many head/neck cancer survivors, indicating a need for development of more effective smoking cessation interventions. Kava's properties as a proven anxiolytic and carcinogen detoxifier warrant an investigation of its efficacy as an innovative smoking cessation aid. Kava may also influence carcinogen (NNK specifically) metabolism to help reduce carcinogenesis risk.

Conditions

Kava on the Metabolism of Nicotine and NNK

Keywords

kava; tobacco; cessation; cancer; nicotine; NNK; metabolism; carcinogen

Outcome Measures

Primary Outcomes (5)

• Total NNAL

  Total NNAL (the creatinine-normalized sum of NNAL, NNAL-N-gluc, and NNAL-O-gluc) will be calculated via urinary analysis at the screening visit and the final study visit to determine kava's effect on the pharmacokinetics and metabolism of carcinogens \[NNK: 4-(methylnitrosamino)-1-3(pyridyl)-1-butanone\].

  Two weeks

• The ratio of total NNAL-gluc to NNAL

  The ratio of total NNAL-gluc to NNAL will be calculated via urinary analysis at the screening visit and the final study visit to determine kava's effect on the pharmacokinetics and metabolism of carcinogens \[NNK: 4-(methylnitrosamino)-1-3(pyridyl)-1-butanone\].

  Two weeks

• The urinary DNA adducts of 3-mA upon TNE correction

  The urinary DNA adducts of 3-mA upon TNE correction will be calculated via urinary analysis at the screening visit and the final study visit to determine kava's effect on the pharmacokinetics and metabolism of carcinogens \[NNK: 4-(methylnitrosamino)-1-3(pyridyl)-1-butanone\].

  Two weeks

• The ratio of total NNAL to TNE

  The ratio of total NNAL to TNE (the creatinine-normalized sum of total nicotine, total cotinine, total 3-hydroxycotinine, and nicotine N-oxide) will be calculated via urinary analysis at the screening visit and the final study visit to determine kava's effect on the pharmacokinetics and metabolism of carcinogens \[NNK: 4-(methylnitrosamino)-1-3(pyridyl)-1-butanone\].

  Two weeks

• The DNA adducts in the buccal cells from oral swab

  The DNA adducts in the buccal cells will be calculated via oral swab at the screening visit and the final study visit to determine kava's effect on the pharmacokinetics and metabolism of carcinogens \[NNK: 4-(methylnitrosamino)-1-3(pyridyl)-1-butanone\].

  Two weeks

Secondary Outcomes (3)

• Positive and Negative Affect Scale (PANAS)

  Two weeks

• WHO Quality of Life BREF (WHOQOL-BREF)

  Two weeks

• Brief Pain Inventory Questionnaire

  Two weeks

Other Outcomes (5)

• Minnesota Nicotine Withdrawal Scale (MNWS)

  Two weeks

• Fagerstrom Test Nicotine Dependence (FTND)

  Two weeks

• Brief Questionnaire of Smoking Urges (QSU-Brief)

  Two weeks

Study Arms (1)

Kava

EXPERIMENTAL

This is a single-arm pre- and post- Phase 0/1 study with one primary goal to explore the feasibility of recruitment of participants, adherence rate, acceptability of treatment and completion rate with 14 day dietary supplement kava treatment in head and neck cancer patients who continue to smoke. The other primary goal is to evaluate distribution of change in nicotine and NNK metabolism after 14 day kava treatment..

Drug: Kava

Interventions

Kava DRUG

Kava: 75 mg three times daily (3 capsules)

Kava

Eligibility Criteria

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

You may qualify if:

• Individuals eligible for study participation must meet the following criteria:
• Must be a current smoker with history of head and neck cancer.
• Must be at least 3 months out from completing definitive cancer treatment.
• Must not be undergoing active treatment for cancer or have known recurrence.
• Subjects must have adequate organ function, as defined by: the clinical chemistry analysis of ALT, ALP, AST and total bilirubin within the normal range.
• Subjects must have access to a functional telephone.
• Written informed consent obtained from the subject or the subject's legal representative and the ability for the subject to comply with all the study-related procedures.
• Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study. Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.
• WOCBP include any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who is not post-menopausal. Post-menopause is defined as:
• Amenorrhea that has lasted for ≥ 12 consecutive months without another cause, or
• For women with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL.
• Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study.

You may not qualify if:

• Subjects with any of the following will not be eligible for study participation:
• Known liver disease as defined by the following elevated serum levels of AST, ALK Phos, ALT or total bilirubin:
• Consumption of more than three alcoholic drinks per day
• D. Subjects must not have been diagnosed with any liver dysfunction
• Subjects who regularly take more than the recommended dose of acetaminophen for pain management.
• Females or males of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period.
• Females who are pregnant or breastfeeding.
• History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy or that might affect the interpretation of the results of the study or that puts the subject at high risk for treatment complications, in the opinion of the treating physician.
• Prisoners or subjects who are involuntarily incarcerated.
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness.
• Subjects demonstrating an inability to comply with the study and/or follow-up procedures.

Sponsors & Collaborators

• University of Florida: lead

MeSH Terms

Conditions

Neoplasms

Study Officials

• Natalie Silver, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-Arm Pre- and Post- Trial

Study Record Dates

• First Submitted: July 20, 2018
• First Posted: July 31, 2018
• Study Start: January 1, 2020
• Primary Completion: October 1, 2020
• Study Completion: January 1, 2021
• Last Updated: January 13, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share