Broccoli Sprout Extracts in Healthy Volunteers: A Pilot Study of Nrf2 Pathway Modulation in Oral Mucosa

NCT02023931 | Completed Early Phase 1 DMC

• 2 other identifiers: 13-0795P50CA097190-09
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

A pilot study has been designed to determine (primary objective) if three brief interventions with three oral BSE regimens will alter mRNA biomarkers of Nrf2 pathway signaling, including NQO1, GSTs and AKRs, in the oral mucosa of healthy subjects. Quantitative distribution data and preliminary effect size for specific Nrf2 targets, as measured in serial buccal cell scrapings, will be determined during the course of 3-day exposures to three BSE regimens. These data will inform the design of a randomized, phase II chemoprevention trial in patients with HPV-negative HNSCC. Ten healthy volunteers will be recruited for this pilot study, Age ≥ 18 years, both male and female: 1) The non-cancer population presenting to the University of Pittsburgh Eye and Ear Institute or the Hillman Cancer Center. This may include patients with benign disease or their friends/family members, or friends/family members of patients with cancer; 2) Professionals, staff, or students at the University of Pittsburgh.

Conditions

Healthy Subject

Keywords

Oral mucosa; Nrf2 pathway; Broccoli Sprout Extract; Head and Neck Cancer

Outcome Measures

Primary Outcomes (1)

• Determine the modulation of the Nrf2 pathway in response to short term exposure to three BSE regimens

  The primary objective is limited to obtaining preliminary estimates of Nrf2 pathway modulation from buccal cell specimens samples all collected during each of the three 5 day intervention periods. Endpoints include mRNA transcript levels of certain genes or enzymes regulated by Nrf2. Note that the goals of this study are limited to obtaining initial pharmacodynamic estimates of Nrf2 pathway modulation for each BSE intervention. Accordingly, no hypothesis testing or comparative analyses are planned. The data collected in this pilot study may be used to plan a future definitive prevention trial.

  Three to 11 weeks

Secondary Outcomes (1)

• Estimate modulation of Nrf2 pathway markers in PBMCs and metabolites of SFN in urine

  Three to 11 weeks

Study Arms (1)

Broccoli Sprout Extract Drink

EXPERIMENTAL

Three different regimens of BSE delivery will be evaluated in each participant, with participants serving as their own controls. Each regimen will involve a 3 day exposure, with daily collection of buccal cell scrapings. Between regimens, a minimum 3 day (72 hour) washout period will occur.

Drug: Broccoli Sprout Extract (BSE)

Interventions

Broccoli Sprout Extract (BSE) DRUG

1. The first regimen will involve oral delivery and ingestion of 600 μmole doses of glucoraphanin-rich BSE (GRR-BSE), and will represent systemic delivery of sulforaphane to oral mucosa, due to the necessity to metabolize GRR-BSE in the gut. 2. The second regimen will involve oral delivery and ingestion of 100 μmole doses of sulforaphane-rich BSE (SFR-BSE), which will represent a combination of systemic and topical delivery to the oral mucosa. 3. The third regimen will isolate topical exposure of the oral mucosa to sulforaphane. Participants will swish, hold, then spit 100 μmole doses of SFR-BSE. This regimen (SFR-BSE(T)) will theoretically isolate the pharmacodynamic impact of topical exposure of the oral mucosa to sulforaphane.

Also known as: Glucoraphanin-rich BSE (GRR-BSE), Sulforaphane-rich BSE (SFR-BSE)

Broccoli Sprout Extract Drink

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years. Children will not be recruited into this study because children do not develop head and neck cancer.
• Both males and females are eligible.
• Members of all racial and ethnic groups are eligible.
• Smoking and non-smoking people are eligible. The tobacco use assessment form must be completed following consent and registration (Appendix B).
• No current or former diagnosis of cancer, with the exception of: excised and cured non-melanoma skin cancer; or carcinoma in situ of the cervix
• No use of chronic prescribed medications which are potent inducers or inhibitors of CYP3A4 (Appendix A)
• No chronic anticoagulation
• No chronic use of steroids
• Karnofsky Performance Scale ≥90% (Appendix C)
• Able to provide written, informed consent
• For women of child-bearing potential (WOCBP), a negative urine pregnancy test must be documented within 7 days prior to the first study intervention
• No history of food intolerance to broccoli or pineapple and lime juices
• Willing to avoid cruciferous vegetables during the study interventions (Appendix D)
• Willing to avoid grapefruit or grapefruit juice 48 hours prior to or during the study
• Willing to avoid daily vitamins and anti-inflammatory medications prior to and during the study

You may not qualify if:

• Failure to meet the above criteria

Sponsors & Collaborators

• Julie E. Bauman, MD, MPH: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Eye and Ear Institute

Pittsburgh, Pennsylvania, 15213, United States

Location

UPMC Hillman Cancer Center (University of Pittsburgh Cancer Institute)

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Study Officials

• Julie E Bauman, MD

  University ofPittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine,Director of the Section of Head and Neck Cancer

Study Record Dates

• First Submitted: December 24, 2013
• First Posted: December 30, 2013
• Study Start: March 1, 2014
• Primary Completion: April 1, 2014
• Study Completion: January 1, 2015
• Last Updated: November 13, 2017

Record last verified: 2017-11

Locations

US (2)