Effect of Sulforaphane-rich Broccoli Sprout Homogenate on Ozone Induced Inflammation Through Modulation of NRF2 — BroccOz  

Healthy Clinical Trial

Official title: Down Regulation of Oxidant Induced Airway Inflammation Through Modulation of NRF2

Status Completed

Clinical Trial Summary

Purpose: To determine if modulation of NRF2 with a Sulforaphane enriched supplement modifies responses to O3. Participants: Recruitment of up to 70 healthy volunteers, ages 18-50, for completion of 36 volunteers. Procedures: This is a randomized, placebo controlled 2x2 crossover study of treatment with an NRF2 modifier versus placebo in healthy volunteers which will examine airway inflammation before and 4 hours after a 2 hour 0.4 ppm O3 exposure. Participants will be randomized to received either the NRF2 modifier, SFN oral supplement (i.e. broccoli sprout shake), or placebo (alfalfa shake) for 3 days followed by a 0.4 ppm O3 exposure for 2 hours. At least 2 weeks later subjects will return for a 2nd supplementation treatment (using the alternative supplement to that provided initially) followed by an ozone exposure identical to the initial one.

Clinical Trial Description

Potential subjects will be seen for a baseline screening visit at which time informed consent will be obtained, a 12 lead ECG will be performed and spirometry with subsequent sputum induction will be performed. Only subjects meeting the lung function criteria as well as criteria for adequate sputum production will continue in the study. If the sample is considered "borderline" by the study team, the subject maybe invited back to repeat collection of another sputum sample. Subjects will be required to abstain from caffeine for 12 hours prior to all study visits and must not use/ingest non-steroidal anti-inflammatory medications, anti-oxidant vitamins, juices/drinks fortified with extra vitamin supplement and cruciferous vegetables 7 days prior to all visits. Subjects will be provided with a list of cruciferous vegetables.

Qualified volunteers will next be seen for a training visit at which time they will undergo physical exam by a study physician. After baseline spirometry is evaluated, the subject will exercise on a treadmill, and measurements of minute ventilation will be collected. Treadmill speed and/or elevation will be adjusted until the subject's minute ventilation is at the target level of 30-40 L/min. The resulting speed and elevation will be used during the ozone exposure sessions. At the training visit, participants will also undergo nasal epithelial biopsy from one nare, and a buccal swab will be collected for genotyping. Baseline blood samples will also be collected at this time for analyses of markers of inflammation, cytokine assessments, SFN levels and complete blood cell count with differential.

After completion of the training session, the subject will return for 4 sequential days. During the first 3 days, subjects will ingest (observed ingestion) either broccoli sprout homogenate or alfalfa sprout homogenate based on earlier randomization. One hour after the supplement dose on the 3rd day, the volunteer will undergo exposure to 0.4 ppm ozone for a 2 hour period. During exposure, subjects will perform 15 minutes of moderate exercise on a treadmill (minute ventilation = 30-40 L/min), each separated by 15 minutes of seated rest. Heart rate and rhythm will be continuously monitored throughout the exposure. Spirometry and symptom scoring will be performed both prior to and after exposure. One hour after the end of exposure, a nasal epithelial biopsy will be collected from the nare that is contralateral to that used at the prior visit. Four hours after completion of the exposure, blood will be drawn for study endpoints and a sputum induction will be performed. The following day the subject will return for a follow-up visit to include vital signs, symptom scoring, spirometry, sputum induction and venipuncture for blood endpoints.

Subjects will be required to abstain from a list of vegetables for 1 week prior to each study session until the completion of that session. Subjects will also be asked to maintain a food diary for the same time.

After a 2 to 6 weeks washout period, participants will again return for a repeated sequence of 4 days with 3 days of supplement ingestion followed by ozone exposure using the alternate supplement and a 24 hour post exposure follow-up visit. Samples for analyses will be collected at the same time points as those used in the initial sequence. ;

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Healthy
• Inflammation

• NCT number: NCT01625130
• Study type: Interventional
• Source: University of North Carolina, Chapel Hill
• Status: Completed
• Phase: N/A
• Start date: October 2013
• Completion date: June 2015