Investigation of Kava Effects on NNK Metabolism

Study Overview
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Brief Summary
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This is a non-therapeutic, single-arm pilot clinical trial in adult healthy smokers to assess whether kava can alter NNK metabolism in humans.

Official Title
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Investigation of Kava Effects on the Metabolism of the Tobacco-specific Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in Humans

Conditions
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Tobacco Smoking

Intervention / Treatment
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* Dietary Supplement: Kava


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult ≥ 18 years Current smoker of ≥ 5 cigarettes daily, determined by self-report Adequate liver and kidney function, defined as: Bilirubin, alkaline phosphatase, ALT, and AST within normal limits Creatinine <1.2 Adequate hemoglobin, defined as a hemoglobin ≥12 mg/dL for men and ≥11 for women. Ability and willingness to abstain from all medication and dietary supplements for 3 days prior to kava administration, continuing until a minimum of 7 days after kava administration. Topical medications and inhaled medications that do not contain steroids are permitted. Ability and willingness to completely abstain from alcohol consumption for 3 days prior to kava administration, continuing until a minimum of 7 days after kava administration Ability to understand the investigational nature of the study and provide informed consent Willingness to take kava supplement as instructed Exclusion Criteria: Known hepatobiliary disease or impairment History of gastric bypass surgery, gastric banding, bowel resection, malabsorption syndromes such as celiac sprue or pancreatic insufficiency, or other conditions that may affect the absorption of kava Chronic medication use that cannot be safely stopped Use of tobacco products other than cigarettes (i.e. snuff, snuz, smokeless tobacco, cigars, pipes) Major or chronic medical medical disease, including heart disease, poorly controlled diabetes, etc., to be adjudicated by the principal investigator Women who are pregnant, intend to become pregnant within 3 months of the study period, or who are breastfeeding Current or recent (within 12 months) problems with drug use or alcohol dependence by self-report Antibiotic use within 2 months of study enrollment by self-report Alcohol dependence, abuse, or history of dependence/abuse by self-report

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Kava Supplement<br>See intervention description. | Dietary Supplement: Kava<br>* 3 doses equaling 250 mg kavalactones per day. Participants will take 1 capsule three times daily at 8:00 (± 2 hours), 14:00 (± 2 hours) and 20:00 (± 2 hours) for 7 consecutive days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary level (nmol/mL) of total NNAL before and after short-term kava administration | Compare urinary level of total NNAL before and after short-term kava administration | Day 1 | 
| Urinary level (nmol/mL) of total NNAL before and after short-term kava administration | Compare urinary level of total NNAL before and after short-term kava administration | Day 2 | 
| Urinary level (nmol/mL) of total NNAL before and after short-term kava administration | Compare urinary level of total NNAL before and after short-term kava administration | Day 4 | 
| Urinary level (nmol/mL) of total NNAL before and after short-term kava administration | Compare urinary level of total NNAL before and after short-term kava administration | Day 5 | 
| Urinary level (nmol/mL) of total NNAL before and after short-term kava administration | Compare urinary level of total NNAL before and after short-term kava administration | Day 6 | 
| Urinary level (nmol/mL) of total NNAL before and after short-term kava administration | Compare urinary level of total NNAL before and after short-term kava administration | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of urinary NNAL-gluc (nmol/mL) and free NNAL (nmol/mL) before and after short-term kava administration | Compare the ratio of urinary NNAL-gluc and free NNAL before and after short-term kava administration | Day 1 | 
| Ratio of urinary NNAL-gluc (nmol/mL) and free NNAL (nmol/mL) before and after short-term kava administration | Compare the ratio of urinary NNAL-gluc and free NNAL before and after short-term kava administration | Day 2 | 
| Ratio of urinary NNAL-gluc (nmol/mL) and free NNAL (nmol/mL) before and after short-term kava administration | Compare the ratio of urinary NNAL-gluc and free NNAL before and after short-term kava administration | Day 4 | 
| Ratio of urinary NNAL-gluc (nmol/mL) and free NNAL (nmol/mL) before and after short-term kava administration | Compare the ratio of urinary NNAL-gluc and free NNAL before and after short-term kava administration | Day 5 | 
| Ratio of urinary NNAL-gluc (nmol/mL) and free NNAL (nmol/mL) before and after short-term kava administration | Compare the ratio of urinary NNAL-gluc and free NNAL before and after short-term kava administration | Day 6 | 
| Ratio of urinary NNAL-gluc (nmol/mL) and free NNAL (nmol/mL) before and after short-term kava administration | Compare the ratio of urinary NNAL-gluc and free NNAL before and after short-term kava administration | Day 7 | 
| Percentage of subjects experiencing any particular adverse event | Determine the safety of short-term kava administration in healthy smokers | Day 4 | 
| Percentage of subjects experiencing any particular adverse event | Determine the safety of short-term kava administration in healthy smokers | Day 7 | 
| O6-mG adducts level (fmol) in peripheral blood cells before and after short-term kava administration | Quantify O6-mG adducts in peripheral blood cells before and after short-term kava administration | Day 4 | 
| O6-mG adducts level (fmol) in peripheral blood cells before and after short-term kava administration | Quantify O6-mG adducts in peripheral blood cells before and after short-term kava administration | Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tobacco, Smoking