Effects of Sulforaphane (SFN) on Immune Response to Live Attenuated Influenza Virus in Smokers and Nonsmokers

NCT01269723 | Completed

• 2 other identifiers: 10-1806R01HL095163-02
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Smoking

Keywords

Smoking; influenza; influenza vaccine

Outcome Measures

Primary Outcomes (1)

• Interleukin 6 (IL-6) in NL after LAIV inoculation (expressed as area under curve for ratio of IL-6 to baseline) in smokers

  This will be performed by repetitive spraying of sterile normal saline irrigation solution (5 ml total) into the nostril, followed by voluntary expelling of fluid by the subject into a specimen collection cup. Both nostrils are lavaged in this way and the resulting nasal lavage fluid (NLF) from both sides is combined.

  at days 1, 2 ,3, 7 and 21 post LAIV

Secondary Outcomes (1)

• change in nasal cells-cytokines, chemokines, natural killer cell activation; tolerance of homogenate; nasal biopsy Nrf2, cytokine, and phase II enzyme mRNA; serum antibodies; blood cell response to influenza antigen

  For nasal lavage-at days 1, 2 ,3, 7 and 21 post LAIV; for biopsy samples taken on Days 2 and 7 post LAIV; for blood endpoints-Days 2 and 21 post LAIV

Study Arms (2)

Broccoli sprout homogenate

ACTIVE COMPARATOR

The broccoli sprouts and water are chopped in a blender until a uniform mix is obtained. Salt or sugar may be added to the "shake".

Dietary Supplement: Broccoli sprout homogenate

alfalfa sprout homogenate

PLACEBO COMPARATOR

Alfalfa sprouts and water are chopped in a blender until a uniform mix is obtained. Salt or sugar may be added to the "shake".

Dietary Supplement: Alfalfa sprout homogenate

Interventions

Broccoli sprout homogenate DIETARY_SUPPLEMENT

Subjects will drink the broccoli shake homogenate

Also known as: Broccoli sprout shake

Broccoli sprout homogenate

Alfalfa sprout homogenate DIETARY_SUPPLEMENT

Subjects will drink the alfalfa sprout homogenate.

Also known as: Alfalfa sprout shake

alfalfa sprout homogenate

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults, age 18-40 yr who are either nonsmokers OR smokers (\> 0.5 pack/day);
• Willing to avoid corticosteroids and nonsteroidal anti-inflammatory medications for 1 week prior to study entry and again for 1 week prior to all remaining visits;
• Willing to avoid antioxidant vitamins and cruciferous vegetables as well as juices/drinks with vitamin supplements added for 2 days prior to Day (-1) of the protocol and throughout the subsequent study.

You may not qualify if:

• Symptomatic allergies requiring medications for at least a 2 week interval during the past year;
• Respiratory infection (cough, sore throat, sinusitis, fever etc) within prior 4 weeks;
• Current nutritional disorder such as anorexia, bulimia, irritable bowel syndrome, Crohn's disease etc;
• Pregnancy or nursing;
• Asthma (other than wheezing occurring only in childhood); immunodeficiency (HIV or other); or any chronic medical condition that, in the opinion of the investigator, would preclude subject participation;
• Current use of immunosuppressive drugs;
• History of fainting or feeling severely dizzy with blood draws;
• History of hypersensitivity, especially anaphylactic reactions, to egg proteins, gentamicin, gelatin, or arginine or with adverse reactions to previous influenza vaccinations;
• History of Guillain Barre syndrome;
• Smokers who have abnormal lung function on pulmonary function testing at the time of screening (FVC and FEV1 \< 80% of that predicted based on subject age, gender, height and race);
• Subjects who will be unable to avoid contact with immunocompromised individuals for 3 weeks after receiving LAIV vaccine;
• Receipt of any type of influenza vaccine since August 2009;
• Diagnosed influenza illness since August 2009;
• History of intolerance of or aversion to broccoli.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

UNC Center for Environmental Medicine, Asthma and Lung Biology

Chapel Hill, North Carolina, 27599-7310, United States

Location

Related Publications (2)

• Muller L, Meyer M, Bauer RN, Zhou H, Zhang H, Jones S, Robinette C, Noah TL, Jaspers I. Effect of Broccoli Sprouts and Live Attenuated Influenza Virus on Peripheral Blood Natural Killer Cells: A Randomized, Double-Blind Study. PLoS One. 2016 Jan 28;11(1):e0147742. doi: 10.1371/journal.pone.0147742. eCollection 2016.

  PMID: 26820305 DERIVED

• Noah TL, Zhang H, Zhou H, Glista-Baker E, Muller L, Bauer RN, Meyer M, Murphy PC, Jones S, Letang B, Robinette C, Jaspers I. Effect of broccoli sprouts on nasal response to live attenuated influenza virus in smokers: a randomized, double-blind study. PLoS One. 2014 Jun 9;9(6):e98671. doi: 10.1371/journal.pone.0098671. eCollection 2014.

  PMID: 24910991 DERIVED

MeSH Terms

Conditions

Smoking; Influenza, Human

Condition Hierarchy (Ancestors)

Behavior; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Officials

• Terry Noah, MD

  University of North Carolina at Chapel Hill School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: December 14, 2010
• First Posted: January 4, 2011
• Study Start: December 1, 2010
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: January 29, 2014

Record last verified: 2014-01

Locations

US (1)