Effect of Sulforaphane in Broccoli Sprouts on Nrf2 Activation

Study Overview
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Brief Summary
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The purpose of this study to investigate the effect of sulforaphane from macerated broccoli sprouts in humans and to evaluate less invasive methods of assessing potential anti-inflammatory drugs in CF.

Detailed Description
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The hypothesis to be tested is that sulforaphane consumed from macerated broccoli sprouts will activate Nrf2, reduce oxidative metabolites and reduce neutrophils in the oral mucosa after 5 days of therapy in healthy volunteers and CF subjects. The study requires 6 brief outpatient visits over 8 days. Study procedures include medical history, height, weight, vital signs, blood and urine collection, nasal curettage, saline mouthwash, and ingestion of broccoli sprouts (100 gm of 3 to 5 day old raw broccoli sprouts once daily for 5 consecutive days).

Official Title
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Evaluation of the Effect of Sulforaphane in Broccoli Sprouts on Nrf2 Activation, Measures of Oxidative Stress, and Neutrophil Migration to Mucosal Surfaces in Healthy and CF Subjects

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Dietary Supplement: Broccoli sprouts


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers and patients with cystic fibrosis ≥ 18 < 50 years of age Healthy volunteers must be in general good health as determined by a medical history CF subjects must have a documented diagnosis of CF (positive sweat chloride ≥ 60 mEq/liter, by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF accompanied by one or more clinical features with the CF) phenotype CF subjects must have a baseline FEV1 percent predicted > 50% (in the last year, obtained from medical record) CF subjects must be clinically stable: free of any acute illness for > 14 days CF subjects must not have been prescribed any new systemic antibiotics for the 14 days prior to enrollment Ability to provide written informed consent Ability to adhere to the protocol Exclusion Criteria: Use of NSAIDS (e.g., ibuprofen) or corticosteroids including inhaled steroids for the 4 weeks prior to enrollment Active gingival disease (active tooth or gum disease) History of nephrolithiasis or cholelithiasis Allergy to broccoli Any chronic condition that compromises the participant as determined by medical history Pregnancy Inability to tolerate the study procedures CF subjects: Infected with B. cepacia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy volunteers<br>100 grams of raw broccoli sprouts once daily for 5 consecutive days | Dietary Supplement: Broccoli sprouts<br>* Subjects (both healthy volunteers and subjects with cystic fibrosis) will consume 100 gm of raw broccoli sprouts once daily for 5 consecutive days.<br>* Other names: sulforaphane;|
| Experimental: Subjects with cystic fibrosis<br>100 grams of raw broccoli sprouts once daily for 5 consecutive days | Dietary Supplement: Broccoli sprouts<br>* Subjects (both healthy volunteers and subjects with cystic fibrosis) will consume 100 gm of raw broccoli sprouts once daily for 5 consecutive days.<br>* Other names: sulforaphane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nrf2 Activation in Nasal Epithelial Cells | Number of subjects with activated Nrf-2 in the cytoplasm of nasal epithelial cells after 5 days of study treatment (consuming broccoli sprouts) | Baseline and of end of 5 day treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measures of Lipid Peroxidation in Nasal Epithelial Cells | Products of lipid peroxidation will be determined by western blot analysis on nasal epithelial cells obtained by curettage after 5 days of study treatment (consuming broccoli sprouts) | End of 5 day treatment period | 
| Measures of Glutathione From Blood Lymphocytes | Change in lymphocyte glutathione measurements after 5 days of study treatment (consuming broccoli sprouts). | Baseline and end of 5 day treatment period | 
| Measures of Oxidative Stress in Urine | Change in urine bromotyrosine (measured by mass spectrometry) will be measured after 5 days of study treatment (consuming broccoli sprouts). | Baseline and end of 5 day treatment period | 
| Measure of Neutrophil Migration Into the Gingival Crevices | Change in gingival neutrophils measured after 5 days of study treatment (consuming broccoli sprouts). Patients will perform mouthwashes with normal saline. Neutrophil counts will be performed on fresh samples. Acridine orange will be added to the saline rinses and neutrophils will be counted under the microscope. | Baseline and end of 5 day treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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broccoli sprouts, sulforaphane, triterpenoid, Nrf2 activation, cystic fibrosis, healthy volunteers, anti-inflammatory