Prevention of Oral DNA Damage by Black Raspberries

Effect of Oral Black Raspberry Administration on Oral Cell DNA Adducts in Smokers

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.

Study Overview

• Status: Completed
• Conditions: Smoking; Oxidative Stress; Oral Cancer; DNA Damage
• Intervention / Treatment: Dietary supplement: BRB Lozenges

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.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State CTSI Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BRB Lozenges; Oral lozenges that contain 1 gram of BRB freeze-dried powder	Dietary supplement: BRB 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HPB-releasing Adducts (Buccal Cells)	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).	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
B[a]P Adducts (Buccal Cells)	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 weeks
8-OXO-dG (Buccal Cells)	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.	8 weeks
Cotinine (Urine)	Biomarker of tobacco smoke exposure	8 weeks
Creatinine (Urine)	Biomarker of urine dilution	8 weeks
8-Isoprostane (Urine)	Biomarker of systemic oxidative stress	8 weeks

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Karam P El-Bayoumy, Ph.D, Penn State University Hershey Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2021
• Primary Completion (Actual): December 6, 2024
• Study Completion (Actual): December 6, 2024

Study Registration Dates

• First Submitted: April 22, 2020
• First Submitted That Met QC Criteria: April 29, 2020
• First Posted (Actual): May 4, 2020

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 2, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Behavior; Mouth Neoplasms; Smoking
• Other Study ID Numbers: STUDY00013621; R01CA173465 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No