Investigation of Kava Effects on NNK Metabolism

Tobacco Smoking Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02500472
• Other study ID #: 2015NTLS038
• Status: Completed
• Phase: N/A
• First received: June 26, 2015
• Last updated: April 2, 2018
• Start date: December 3, 2015
• Est. completion date: March 2018

Study information

• Verified date: December 2017
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: March 2018
• Est. primary completion date: March 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Tobacco Smoking

Intervention

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.

Locations

Country	Name	City	State
United States	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percentage of subjects experiencing any particular adverse event	Determine the safety of short-term kava administration in healthy smokers	Day 4
Secondary	Percentage of subjects experiencing any particular adverse event	Determine the safety of short-term kava administration in healthy smokers	Day 7
Secondary	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
Secondary	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