DNA Damage, Oral Cancer, Oxidative Stress, Smoking
Conditions
Brief summary
The purpose of this voluntary research study is to learn about the potential effects that black raspberry (BRB) lozenges may have on reducing the damage caused from cigarette smoke in mouth cells in adult smokers, which may be useful in reducing health risks associated with smoking.
Detailed description
This clinical trial will consist of a single arm, where participants, after a 1-week baseline period, will be placed on daily BRB administration for a period of 8 weeks followed by a 4 week washout period. Prior to study enrollment, all participants will have an Oral Cancer screening intraoral exam and persons with oral pathology (e.g. premalignant or oral squamous cell carcinoma) will be referred for appropriate clinical care. Biological samples will be collected at 0, 1, 4, 5, 8, 9, 12 and 13 weeks. An 8-week BRB administration period was selected to allow for ample time for effects to be observed in the major endpoints, based on previous clinical data. Likewise, a 4 week washout period at the end of the trial will allow for effects of BRB withdrawal on major outcomes to be measured. A total of 58 healthy subjects will be recruited into this intervention study. Eligible subjects, after phone screening, will visit the clinic for an additional in-person screening which includes measurement of expired carbon monoxide and pregnancy test (females). Prior to enrollment, each subject will be offered a free oral cancer screening. After obtaining informed consent, eligible subjects will be administered a questionnaire to obtain information on basic demographics, medical history, lifestyle, tobacco and alcohol consumption, and usual dietary intake and biological samples (exfoliated buccal cells and urine) and anthropometric data (e.g. height and weight) will be collected. Subjects will be asked to return after 1 week (Visit 2, 2nd baseline visit) and biological samples will be collected. Subjects will be provided their first supply of test agent (BRB lozenge) and a usage diary and instructed on the proper method for application and completion of the diary entries. At Visits 3-6 (weeks 4, 5, 8, and 9, respectively) subjects will return any unused product, receive a new batch of lozenges (except for week 9), complete a brief questionnaire on compliance and provide biological samples. At week 9 (Visit 6), subjects will return their study diaries and enter the washout period where no test agent will be provided. At the final visits (Visit 7 and 8, weeks 12 and 13), subjects will provide biological samples.
Interventions
DIETARY_SUPPLEMENTBRB Lozenges
Each lozenge is made from 1 gram of freeze-dried black raspberry powder (equivalent to \~5 black raspberries) in the form of a dissolvable slow-release lozenge.
Sponsors
Milton S. Hershey Medical Center
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 21-75 * Smoke 5 cigarettes per day or more for at least the past 12 months * Have an expired air carbon monoxide measurement of greater than 6 parts per million * No serious quit attempt in the last one month and not planning to quit in the next 4 months * Willing and able to attend all study visits * Able to read and write in English * Able to understand and provide consent to the study procedures * Willingness and ability to attend regular visits over a 14-week period and to respond to research contacts between the 5
Exclusion criteria
* Unstable or significant medical conditions that affect participant safety or biomarker data in the past 3 months (e.g. recent heart attack, asthma or COPD) * Women currently pregnant or nursing * Use of any non-cigarette nicotine delivery product in the past 7 days (e.g. e-cigarettes, pipe or cigar) * Uncontrolled mental illness or inpatient treatment in the past 6 months; current suicide risk on clinical assessment * Any known allergy to raspberries * Use of marijuana or other illegal drugs daily or weekly in the past 3 months * Use of high dose antioxidant supplements in the past month * Use of antibiotics * Heavy drinking (\>4 drinks/day, 5 days/week) * Made no serious cigarette smoking quit attempt or have used any FDA-approved smoking cessation medication in the prior 30 days * No plan to quit smoking within the next 4 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HPB-releasing Adducts (Buccal Cells) | 8 weeks | The tobacco specific nitrosamine, N'-nitrosonornicotine, is metabolically activated to form DNA adduct that upon hydrolysis releases 4-hydroxy-1-(3-pyridyl)-1-butonone (HPB), which was measured in buccal cells of smokers in picogram per microgram guanine (one of the four bases of DNA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| B[a]P Adducts (Buccal Cells) | 8 weeks | Benzo\[a\]pyrene, a tobacco smoke constituent, is metabolized in buccal cells of smoker's into active metabolite namely benzo\[a\]pyrene-diol epoxide (BPDE). BPDE can react with DNA to form deoxyguanosine adducts (BPDE-N\^2-dG) that measured in buccal cells of smokers in picogram per microgram deoxyguanosine. |
| 8-OXO-dG (Buccal Cells) | 8 weeks | Cigarette smoke is a rich source of free radicals that can promote oxidative stress and carcinogenesis, including head and neck squamous cell carcinoma. 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxo-dG) is a valid biomarker of oxidative stress. We measured 8-oxo-dG in buccal cells of smokers and the levels are expressed as picogram per microgram of deoxyguanosine. |
| Cotinine (Urine) | 8 weeks | Biomarker of tobacco smoke exposure |
| Creatinine (Urine) | 8 weeks | Biomarker of urine dilution |
| 8-Isoprostane (Urine) | 8 weeks | Biomarker of systemic oxidative stress |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORKaram P El-Bayoumy, Ph.D
Penn State University Hershey Medical Center
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 47.2 years STANDARD_DEVIATION 11.3 |
| Cigarettes per day | 17.7 cigarettes per day STANDARD_DEVIATION 6.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 68 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 63 Participants |
| Region of Enrollment United States | 69 Participants |
| Sex: Female, Male Female | 45 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 69 |
| other Total, other adverse events | 17 / 69 |
| serious Total, serious adverse events | 4 / 69 |
Outcome results
None listed