Clinical trial NCT03606655: Exploring the Impact of Two-week Kava on the Metabolism of Nicotine and NNK
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Kava on the Metabolism of Nicotine and NNK
Keywords: kava
tobacco
cessation
cancer
nicotine
NNK
metabolism
carcinogen
Lead sponsor: University of Florida
Sponsor class: OTHER
First posted: 2018-07-31
Enrollment: 0
Sex: ALL
Minimum age (years): 21
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single-Arm Pre- and Post- Trial
Primary purpose: SUPPORTIVE_CARE

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Total NNAL
timeFrame: Two weeks
measure: The ratio of total NNAL-gluc to NNAL
timeFrame: Two weeks
measure: The urinary DNA adducts of 3-mA upon TNE correction
timeFrame: Two weeks
measure: The ratio of total NNAL to TNE
timeFrame: Two weeks
measure: The DNA adducts in the buccal cells from oral swab
timeFrame: Two weeks
Secondary outcomes:
measure: Positive and Negative Affect Scale (PANAS)
timeFrame: Two weeks
measure: WHO Quality of Life BREF (WHOQOL-BREF)
timeFrame: Two weeks
measure: Brief Pain Inventory Questionnaire
timeFrame: Two weeks
Other outcomes:
measure: Minnesota Nicotine Withdrawal Scale (MNWS)
timeFrame: Two weeks
measure: Fagerstrom Test Nicotine Dependence (FTND)
timeFrame: Two weeks
measure: Brief Questionnaire of Smoking Urges (QSU-Brief)
timeFrame: Two weeks
measure: Modified Cigarette Evaluation Scale (mCES)
timeFrame: Two weeks
measure: Cancer Patient Tobacco Use Questionnaire (C-TUQ)
timeFrame: Two weeks
Locations:
Study officials:
affiliation: University of Florida
name: Natalie Silver, MD
role: PRINCIPAL_INVESTIGATOR
References: