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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Kava on the Metabolism of Nicotine and NNK

Intervention / Treatment
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* Drug: Kava


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Interventional Model Description: Single-Arm Pre- and Post- Trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Kava<br>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<br>* Kava: 75 mg three times daily (3 capsules)<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kava, tobacco, cessation, cancer, nicotine, NNK, metabolism, carcinogen