Clinical trial NCT02500472: Investigation of Kava Effects on NNK Metabolism
Official title: Investigation of Kava Effects on the Metabolism of the Tobacco-specific Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tobacco Smoking
Keywords: Tobacco
Smoking
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2015-07-16
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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


Eligibility criteria: 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

Primary outcomes:
measure: Urinary level (nmol/mL) of total NNAL before and after short-term kava administration
timeFrame: Day 1
measure: Urinary level (nmol/mL) of total NNAL before and after short-term kava administration
timeFrame: Day 2
measure: Urinary level (nmol/mL) of total NNAL before and after short-term kava administration
timeFrame: Day 4
measure: Urinary level (nmol/mL) of total NNAL before and after short-term kava administration
timeFrame: Day 5
measure: Urinary level (nmol/mL) of total NNAL before and after short-term kava administration
timeFrame: Day 6
measure: Urinary level (nmol/mL) of total NNAL before and after short-term kava administration
timeFrame: Day 7
Secondary outcomes:
measure: Ratio of urinary NNAL-gluc (nmol/mL) and free NNAL (nmol/mL) before and after short-term kava administration
timeFrame: Day 1
measure: Ratio of urinary NNAL-gluc (nmol/mL) and free NNAL (nmol/mL) before and after short-term kava administration
timeFrame: Day 2
measure: Ratio of urinary NNAL-gluc (nmol/mL) and free NNAL (nmol/mL) before and after short-term kava administration
timeFrame: Day 4
measure: Ratio of urinary NNAL-gluc (nmol/mL) and free NNAL (nmol/mL) before and after short-term kava administration
timeFrame: Day 5
measure: Ratio of urinary NNAL-gluc (nmol/mL) and free NNAL (nmol/mL) before and after short-term kava administration
timeFrame: Day 6
measure: Ratio of urinary NNAL-gluc (nmol/mL) and free NNAL (nmol/mL) before and after short-term kava administration
timeFrame: Day 7
measure: Percentage of subjects experiencing any particular adverse event
timeFrame: Day 4
measure: Percentage of subjects experiencing any particular adverse event
timeFrame: Day 7
measure: O6-mG adducts level (fmol) in peripheral blood cells before and after short-term kava administration
timeFrame: Day 4
measure: O6-mG adducts level (fmol) in peripheral blood cells before and after short-term kava administration
timeFrame: Day 7
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Naomi Fujioka, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wang Y, Fujioka N, Xing C. Quantitative profiling of cortisol metabolites in human urine by high-resolution accurate-mass MS. Bioanalysis. 2018 Dec;10(24):2015-2026. doi: 10.4155/bio-2018-0182. Epub 2018 Nov 6.