Investigation of Kava Effects on NNK Metabolism

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

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

Study Overview

• Status: Completed
• Conditions: Tobacco Smoking
• Intervention / Treatment: Dietary supplement: Kava

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center, University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Kava Supplement; See intervention description.	Dietary supplement: Kava; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2015
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): March 1, 2018

Study Registration Dates

• First Submitted: June 26, 2015
• First Submitted That Met QC Criteria: July 14, 2015
• First Posted (Estimate): July 16, 2015

Study Record Updates

• Last Update Posted (Actual): April 4, 2018
• Last Update Submitted That Met QC Criteria: April 2, 2018
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Smoking; Tobacco
• Other Study ID Numbers: 2015NTLS038