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: Recruiting
• 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 (Anticipated): 58
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nicolle Krebs, MS; Phone Number: 7175315673; Email: nkrebs@pennstatehealth.psu.edu
• Study Contact Backup: Name: John P Richie, Ph.D; Phone Number: 7175317178; Email: jrichie@pennstatehealth.psu.edu

Study Locations

• United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Recruiting
      • Penn State CTSI Clinical Research Center
      • Contact: Charity Sauder

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

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: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

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
Change of HPB-releasing adducts (buccal cells) from Baseline to end of BRB lozenge treatment at 8 weeks	Marker of DNA damage caused by tobacco specific nitrosamines in tobacco smoke	Baseline, end of 8-week BRB treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of B[a]P adducts (buccal cells) from Baseline to end of BRB lozenge treatment at 8 weeks	Marker of DNA damage caused by benzo[a]pyrene in tobacco smoke	Baseline, end of 8-week BRB treatment
Change of 8-OXO-dG (buccal cells) from Baseline to end of BRB lozenge treatment at 8 weeks	Biomarker of oxidative damage to DNA caused by tobacco smoke	Baseline, end of 8-week BRB treatment
Change of Anthocyanin (buccal cells) from Baseline to end of BRB lozenge treatment at 8 weeks	Biomarker of exposure to the black raspberry chemopreventive anthocyanins	Baseline, end of 8-week BRB treatment
Change of Cotinine (urine) from Baseline to end of BRB lozenge treatment at 8 weeks	Biomarker of tobacco smoke exposure	Baseline, end of 8-week BRB treatment
Change of Creatinine (urine) from Baseline to end of BRB lozenge treatment at 8 weeks	Biomarker of urine dilution	Baseline, end of 8-week BRB treatment
Change of 8-IsoP (urine) from Baseline to end of BRB lozenge treatment at 8 weeks	Biomarker of systemic oxidative stress	Baseline, end of 8-week BRB treatment

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 7, 2021
• Primary Completion (ANTICIPATED): September 1, 2024
• Study Completion (ANTICIPATED): September 1, 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): December 1, 2022
• Last Update Submitted That Met QC Criteria: November 29, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Stomatognathic Diseases; Mouth Diseases; Mouth Neoplasms
• Other Study ID Numbers: STUDY00013621; R01CA173465 (NIH)

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