Effects of Sulforaphane (SFN) on Immune Response to Live Attenuated Influenza Virus in Smokers and Nonsmokers
Condition: Smoking
MeSH terms: Influenza, Human
Study type: Interventional

Summary: 
      Vegetables such as broccoli, cauliflower, kale and cabbage are particularly rich in a plant
      chemical called sulforaphane (SFN) which boosts production of certain "defense" enzymes that
      increase the activity of antioxidants. In animals, the chemical protection from SFN helps
      prevent diseases associated with inflammation and cancer among others, and this is currently
      being studied in humans.

      Young broccoli sprouts have a particularly high level of SFN compared to other foods. The
      purpose of this research study is to learn about short term responses to live attenuated
      influenza virus (LAIV, administered to you via Flumist® vaccine) between smoking and
      nonsmoking volunteers treated with broccoli sprout homogenates ("shake") or a placebo
      homogenate. This will be done by obtaining a series of "nasal lavages" or rinses of your nose
      with salt water, as well as 3 superficial biopsies of the inside lining of your nose both
      before and after you receive the vaccine. Using these samples, we will measure the amount of
      virus and the amount of inflammation in your nose and compare how smokers and nonsmokers
      respond to the vaccine when they are given a broccoli sprout homogenate (high in SFN) or a
      placebo alfalfa spout "shake" which is low in SFN during each of 4 study visits.

      Subjects will be seen for a screening visit (inc. HIV test) and then randomly assigned to
      receive 1 of 2 homogenates. Broccoli sprout homogenate will be the the active treatment arm
      while the placebo arm will be alfalfa sprout homogenate. Two to 4 weeks after screening,
      subjects will return for 5 sequential visits (Monday-Friday). Monday-Thursday they will
      receive the assigned homogenate. On Tuesday, they will receive the Flumist®vaccine. Subjects
      will also be seen at 1 and 3 weeks post vaccine. Nasal lavage (NL), blood samples and nasal
      biopsies will performed prior to and after study interventions.
    

Detailed description: 
      Schedule of visits:

      Prior to the screening visit, subjects will be asked to avoid cruciferous vegetables (list
      will be provided to them), corticosteroids and nonsteroidal anti-inflammatory medications for
      1 week prior to the initial visit and again for 1 week prior to all remaining visits. They
      will to also be asked to avoid antioxidant vitamins as well as juices/drinks with added
      vitamin supplements for 2 days prior to enrollment through study completion.

      Baseline screening: obtain informed consent, review medical history, concomitant medications,
      vital signs (VS's), urine collection for analysis of cotinine and SFN metabolites for all
      subjects and urine pregnancy test for females of child bearing potential (all female subjects
      unless they are s/p oophorectomy), physical exam by study MD, complete symptom scoring,
      collect nasal lavage, and nasal biopsy (both nares), buccal swab collection and venipuncture
      (up to 75 cc's) will be performed for human immunodeficiency virus (HIV) test, baseline SFN
      level, immune mediators and SFN-induced gene expression changes. Food diaries will be
      provided with instructions for subjects at this visit

      After successful completion of the screening, the subject will be randomized to receive
      broccoli sprout homogenates or alfalfa sprout homogenates during the next 4 study visits.
      Subjects will return 2-4 weeks after screening for 5 daily sequential visits (Monday through
      Friday).

      Monday (Day -1): VS's, review of concomitant medications, urine collection for analysis of
      cotinine and SFN metabolites for all subjects and Hcg for females of child bearing potential,
      nasal lavage, observed ingestion of initial dose and continue food diaries started 3 days
      prior.

      Tuesday (Day 0): VS's, symptom/adverse event evaluation, review of concomitant medications,
      urine collection for analysis of cotinine and SFN metabolites, observed ingestion of 2nd
      dose, NL, administration of LAIV, continue food diaries.

      Wednesday (Day 1): VS's, symptom/adverse event evaluation, review of concomitant medications,
      urine collection for analysis of cotinine and SFN metabolites, observed ingestion of 3rd
      dose, NL and continue food diaries.

      Thursday (Day 2): VS's, symptom/adverse event evaluation, review of concomitant medications
      and observed ingestion of 4th dose. Two hours after ingestion, urine collection for analysis
      of cotinine and SFN metabolites, venipuncture (up to 10 cc's for SFN level), nasal biopsy
      (left nare) and NL will be performed. Continue food diaries.

      Friday (Day 3): VS's, symptom/adverse event evaluation, review of concomitant medications,
      urine collection for analysis of cotinine and SFN metabolites, NL, continue food diaries.

      Day 7 (+/- 1 day): VS's, symptom/adverse event evaluation, review of concomitant medications,
      urine collection for analysis of cotinine and SFN metabolites, nasal biopsy (right nare), NL,
      continue food diaries.

      Day 21 (+/- 1 week): VS's, symptom/adverse event evaluation, review of concomitant
      medications urine collection for analysis of cotinine and SFN metabolites, NL, venipuncture
      (up to 45 cc's) for immune mediators as well as SFN-induced gene expression changes and
      anti-influenza antibody level, collect completed food diary
    

Intervention name(s): Broccoli sprout homogenate; Alfalfa sprout homogenate
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Subjects will drink the broccoli shake homogenate; Subjects will drink the alfalfa sprout homogenate.
Other intervention name(s): Broccoli sprout shake; Alfalfa sprout shake
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Keywords: Smoking; influenza; influenza vaccine