Kava on the Metabolism of Nicotine and NNKPhase 1NCT03606655
Exploring the Impact of Two-week Kava on the Metabolism of Nicotine and NNK
A Phase 1 study testing Kava in people with Kava on the Metabolism of Nicotine and NNK, run by University of Florida.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 99 years
- Conditions the study is for
- Kava on the Metabolism of Nicotine and NNK
- What is being tested?
- Kava
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jan 2020to Jan 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 12Show fewer
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
About this study
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
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.
Read the 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.
- Being tested
- Kava
- Keywords
- kava, tobacco, cessation, cancer, nicotine, NNK, metabolism, carcinogen
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KavaDrug
Kava: 75 mg three times daily (3 capsules)
| Study group | Role | What they receive |
|---|---|---|
| Kava | Experimental | This is a single-arm pre- and post- Phase 0/1 study with one primary goal 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. The other primary goal is to evaluate distribution of change in nicotine and NNK metabolism after 14 day kava treatment.. Receives: Drug: Kava |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total NNAL
Total NNAL (the creatinine-normalized sum of NNAL, NNAL-N-gluc, and NNAL-O-gluc) will be calculated via urinary analysis at the screening visit and the final study visit to determine kava's effect on the pharmacokinetics and metabolism of carcinogens [NNK: 4-(methylnitrosamino)-1-3(pyridyl)-1-butanone].
Measured: Two weeks
The ratio of total NNAL-gluc to NNAL
The ratio of total NNAL-gluc to NNAL will be calculated via urinary analysis at the screening visit and the final study visit to determine kava's effect on the pharmacokinetics and metabolism of carcinogens [NNK: 4-(methylnitrosamino)-1-3(pyridyl)-1-butanone].
Measured: Two weeks
The urinary DNA adducts of 3-mA upon TNE correction
The urinary DNA adducts of 3-mA upon TNE correction will be calculated via urinary analysis at the screening visit and the final study visit to determine kava's effect on the pharmacokinetics and metabolism of carcinogens [NNK: 4-(methylnitrosamino)-1-3(pyridyl)-1-butanone].
Measured: Two weeks
The ratio of total NNAL to TNE
The ratio of total NNAL to TNE (the creatinine-normalized sum of total nicotine, total cotinine, total 3-hydroxycotinine, and nicotine N-oxide) will be calculated via urinary analysis at the screening visit and the final study visit to determine kava's effect on the pharmacokinetics and metabolism of carcinogens [NNK: 4-(methylnitrosamino)-1-3(pyridyl)-1-butanone].
Measured: Two weeks
The DNA adducts in the buccal cells from oral swab
The DNA adducts in the buccal cells will be calculated via oral swab at the screening visit and the final study visit to determine kava's effect on the pharmacokinetics and metabolism of carcinogens [NNK: 4-(methylnitrosamino)-1-3(pyridyl)-1-butanone].
Measured: Two weeks
Secondary outcomes (3)
Positive and Negative Affect Scale (PANAS)
The efficacy of the dietary supplement kava to positively affect mood will be evaluated via questionnaire. The PANAS scale consists of 20 words that describe different feelings and emotions that can be rated as: 1) Very slightly or not at all 2) A little 3) Moderately 4) Quite a bit 5) Extremely. This questionnaire will be completed at the initial study visit and at the final study visit.
Measured: Two weeks
WHO Quality of Life BREF (WHOQOL-BREF)
Kava's effect on pain and pain medicine consumption will be evaluated via questionnaire. The WHOQOL-BREF instrument comprises 26 items, which measure the following broad domains: physical health, psychological health, social relationships, and environment. This questionnaire will be completed at the initial study visit and at the final study visit.
Measured: Two weeks
Brief Pain Inventory Questionnaire
Kava's effect on pain and pain medicine consumption will be evaluated via questionnaire. The purpose of the BPI is to assess the severity of pain and the impact of pain on daily functions, and focuses on patients with pain from chronic diseases or conditions such as cancer, osteoarthritis and low back pain, or with pain from acute conditions such as postoperative pain. It assesses areas of pain severity, impact of pain on daily function, location of pain, pain medications and amount of pain relief in the past 24 hours or the past week. This questionnaire will be completed at the initial study visit and at the final study visit.
Measured: Two weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2018
- Study startJan 2020 (estimated)
- Primary completionOct 2020 (estimated)
- Study completionJan 2021 (estimated)
Why it stopped: Terms could not be met with the FDA.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kava on the Metabolism of Nicotine and NNKStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single-Arm Pre- and Post- Trial
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Natalie Silver, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03606655
- Sponsor's protocol ID
- IRB201801361
- Other IDs
- UF-PDO-HN-1001, OCR18359
- Status last verified
- Jan 2020
- First submitted
- 20 Jul 2018
- Last updated
- 13 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03606655
- Acronym / sponsor ID
- IRB201801361
- Keywords
- kava, tobacco, cessation, cancer, nicotine, NNK, metabolism, carcinogen
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Terms could not be met with the FDA.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- Jan 2020 (estimated)
- Primary completion
- Oct 2020 (estimated)
- Study completion
- Jan 2021 (estimated)
- First posted
- 31 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single-Arm Pre- and Post- Trial
| Arm | Type | Receives |
|---|---|---|
| Kava | Experimental | Drug: KavaThis is a single-arm pre- and post- Phase 0/1 study with one primary goal 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. The other primary goal is to evaluate distribution of change in nicotine and NNK metabolism after 14 day kava treatment.. |
Who may qualify
- Ages
- 21 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KavaKava: 75 mg three times daily (3 capsules) | Drug | Kava |
Primary outcome
Total NNAL
Time frame: Two weeks
Total NNAL (the creatinine-normalized sum of NNAL, NNAL-N-gluc, and NNAL-O-gluc) will be calculated via urinary analysis at the screening visit and the final study visit to determine kava's effect on the pharmacokinetics and metabolism of carcinogens [NNK: 4-(methylnitrosamino)-1-3(pyridyl)-1-butanone].
The ratio of total NNAL-gluc to NNAL
Time frame: Two weeks
The ratio of total NNAL-gluc to NNAL will be calculated via urinary analysis at the screening visit and the final study visit to determine kava's effect on the pharmacokinetics and metabolism of carcinogens [NNK: 4-(methylnitrosamino)-1-3(pyridyl)-1-butanone].
The urinary DNA adducts of 3-mA upon TNE correction
Time frame: Two weeks
The urinary DNA adducts of 3-mA upon TNE correction will be calculated via urinary analysis at the screening visit and the final study visit to determine kava's effect on the pharmacokinetics and metabolism of carcinogens [NNK: 4-(methylnitrosamino)-1-3(pyridyl)-1-butanone].
The ratio of total NNAL to TNE
Time frame: Two weeks
The ratio of total NNAL to TNE (the creatinine-normalized sum of total nicotine, total cotinine, total 3-hydroxycotinine, and nicotine N-oxide) will be calculated via urinary analysis at the screening visit and the final study visit to determine kava's effect on the pharmacokinetics and metabolism of carcinogens [NNK: 4-(methylnitrosamino)-1-3(pyridyl)-1-butanone].
The DNA adducts in the buccal cells from oral swab
Time frame: Two weeks
The DNA adducts in the buccal cells will be calculated via oral swab at the screening visit and the final study visit to determine kava's effect on the pharmacokinetics and metabolism of carcinogens [NNK: 4-(methylnitrosamino)-1-3(pyridyl)-1-butanone].
3 secondary outcomes
Positive and Negative Affect Scale (PANAS)
Time frame: Two weeks
WHO Quality of Life BREF (WHOQOL-BREF)
Time frame: Two weeks
Brief Pain Inventory Questionnaire
Time frame: Two weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2020.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Natalie Silver, MD principal investigator
University of Florida
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Kava in people with Kava on the Metabolism of Nicotine and NNK, run by University of Florida.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 13 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total NNAL (time frame: Two weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2020.