Effect of Sulforaphane-rich Broccoli Sprout Homogenate on Ozone Induced Inflammation Through Modulation of NRF2
Condition: Healthy
MeSH terms: Inflammation
Study type: Interventional

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.
    

Detailed 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.
    

Intervention name(s): Broccoli sprout homogenate; alfalfa sprout homogenate
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Commercially available Broccosprouts® (Brassica Protection Products LLC) will be homogenized with water using a ratio of 1:1.2 in a clean blender. The homogenate will then be frozen in aliquots at -20 degrees C.; 200 grams of alfalfa sprouts will be homogenized with water using a ratio of 1:1.2 in a clean blender. The homogenate will then be frozen in aliquots at -20 degrees C.
Other intervention name(s): Broccosprouts® (Brassica Protection Products LLC)
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Keywords: sulforaphane; ozone; airway inflammation; broccoli sprouts; NRF2; controls