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

A Single-Arm Pre- and Post-Pilot Trial Exploring the Impact of Two-week Kava on the Metabolism of Two Tobacco Chemicals, Nicotine and NNK, in Head and Neck Cancer Survivors Who Are Active Smokers

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.

Study Overview

• Status: Withdrawn
• Conditions: Kava on the Metabolism of Nicotine and NNK
• Intervention / Treatment: Drug: Kava

Detailed Description

Tobacco smoking is the leading cause of head and neck cancer in the United States and a significant portion of head/neck cancer survivors continue to smoke even though smoking negatively impacts their clinical outcomes and increases chance of recurrence. Two tobacco chemicals, NNK and nicotine, are respectively responsible for the increased recurrence risk and tobacco addiction. Kava s properties as a proven anxiolytic and a potential carcinogen detoxifier warrant an investigation of its effects on the metabolism of these two tobacco chemicals among head/neck cancer survivors who continue to smoke. The results will identifying surrogate biomarkers and provide information regarding kava s potential as a future intervention to both promote smoking cessation and reduce carcinogenesis risk.

Primary Objective:

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.

To evaluate distribution of change in nicotine and NNK metabolism after 14 day kava treatment.

Exploratory Objective:

To evaluate distribution of change in mood after 14 day kava treatment. To evaluate prevalence of pain and pain medication use and distribution of change in pain and pain medication consumption after 14 day kava treatment.

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Kava; 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; Kava: 75 mg three times daily (3 capsules)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive and Negative Affect Scale (PANAS)	The efficacy of the dietary supplement kava to positively affect mood will be evaluated via questionnaire. The PANAS scale consists of 20 words that describe different feelings and emotions that can be rated as: 1) Very slightly or not at all 2) A little 3) Moderately 4) Quite a bit 5) Extremely. This questionnaire will be completed at the initial study visit and at the final study visit.	Two weeks
WHO Quality of Life BREF (WHOQOL-BREF)	Kava's effect on pain and pain medicine consumption will be evaluated via questionnaire. The WHOQOL-BREF instrument comprises 26 items, which measure the following broad domains: physical health, psychological health, social relationships, and environment. This questionnaire will be completed at the initial study visit and at the final study visit.	Two weeks
Brief Pain Inventory Questionnaire	Kava's effect on pain and pain medicine consumption will be evaluated via questionnaire. The purpose of the BPI is to assess the severity of pain and the impact of pain on daily functions, and focuses on patients with pain from chronic diseases or conditions such as cancer, osteoarthritis and low back pain, or with pain from acute conditions such as postoperative pain. It assesses areas of pain severity, impact of pain on daily function, location of pain, pain medications and amount of pain relief in the past 24 hours or the past week. This questionnaire will be completed at the initial study visit and at the final study visit.	Two weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minnesota Nicotine Withdrawal Scale (MNWS)	The efficacy of the dietary supplement kava to reduce tobacco use will be evaluated via questionnaire. The MNWS is used to assess withdrawal symptoms. The nine items of the MNWS included the following: urge to smoke (craving); depressed mood; irritability, frustration, or anger; anxiety; difficulty concentrating; restlessness; increased appetite; difficulty going to sleep; and difficulty staying asleep. Each item was rated by a subject on an ordinal scale from 0 (not at all) to 4 (extreme). This questionnaire will be completed at the initial study visit and at the final study visit.	Two weeks
Fagerstrom Test Nicotine Dependence (FTND)	The efficacy of the dietary supplement kava to reduce tobacco use will be evaluated via questionnaire. The FTND is a standard instrument for assessing the intensity of physical addiction to nicotine. This test was designed to provide an ordinal measure of nicotine dependence related to cigarette smoking. It contains six items that evaluate the quantity of cigarette consumption, the compulsion to use, and dependence. This questionnaire will be completed at the initial study visit and at the final study visit.	Two weeks
Brief Questionnaire of Smoking Urges (QSU-Brief)	The efficacy of the dietary supplement kava to reduce tobacco use will be evaluated via questionnaire. The QSU-Brief questionnaire consists of 10 items comprising four putative features of craving including anticipation of relief of nicotine withdrawal, anticipation of positive outcomes of smoking, desire to smoke, and intention to smoke. This questionnaire will be completed at the initial study visit and at the final study visit.	Two weeks
Modified Cigarette Evaluation Scale (mCES)	The efficacy of the dietary supplement kava to reduce tobacco use will be evaluated via questionnaire. The mCES contains 12 items rated on a 0-6 point Likert scale from 'not at all' to 'extremely'. The mCES is comprised of several subscales: Smoking Satisfaction, Psychological Reward, Aversion, Enjoyment of Respiratory Tract Sensations, and Craving Reduction. This questionnaire will be completed at the initial study visit and at the final study visit.	Two weeks
Cancer Patient Tobacco Use Questionnaire (C-TUQ)	The efficacy of the dietary supplement kava to reduce tobacco use will be evaluated via questionnaire. The C-TUQ is a 22-item self-report survey designed to capture information about tobacco use by cancer patients and cancer survivors. The C-TUQ survey tool is divided into five domains: 1) Basic Tobacco Use Information 2) Cigarette Smoking in Relation to Cancer Diagnosis and Treatment 3) Smoking Cessation, Cessation Products, and Assistance Methods 4) Use of Other Products 5) Second-Hand Smoke Exposure. This questionnaire will be completed at the initial study visit and at the final study visit.	Two weeks

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Natalie Silver, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2020
• Primary Completion (Anticipated): October 1, 2020
• Study Completion (Anticipated): January 1, 2021

Study Registration Dates

• First Submitted: July 20, 2018
• First Submitted That Met QC Criteria: July 20, 2018
• First Posted (Actual): July 31, 2018

Study Record Updates

• Last Update Posted (Actual): January 13, 2020
• Last Update Submitted That Met QC Criteria: January 9, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: cancer; tobacco; metabolism; nicotine; cessation; kava; NNK; carcinogen
• Other Study ID Numbers: IRB201801361; UF-PDO-HN-1001 (Other Identifier: University of Florida); OCR18359 (Other Identifier: University of Florida)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No