Effect of Sulforaphane in Broccoli Sprouts on Nrf2 Activation

Not Applicable

Completed

Brief Summary: 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: 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).

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Healthy volunteers	Broccoli sprouts	100 grams of raw broccoli sprouts once daily for 5 consecutive days
Subjects with cystic fibrosis	Broccoli sprouts	100 grams of raw broccoli sprouts once daily for 5 consecutive days

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Measures of Oxidative Stress in Urine	Baseline and end of 5 day treatment period	Change in urine bromotyrosine (measured by mass spectrometry) will be measured after 5 days of study treatment (consuming broccoli sprouts).
Measure of Neutrophil Migration Into the Gingival Crevices	Baseline and end of 5 day treatment period	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.
Measures of Lipid Peroxidation in Nasal Epithelial Cells	End of 5 day treatment period	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)
Measures of Glutathione From Blood Lymphocytes	Baseline and end of 5 day treatment period	Change in lymphocyte glutathione measurements after 5 days of study treatment (consuming broccoli sprouts).