Cystic Fibrosis
Conditions
Keywords
broccoli sprouts, sulforaphane, triterpenoid, Nrf2 activation, cystic fibrosis, healthy volunteers, anti-inflammatory
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).
Interventions
DIETARY_SUPPLEMENTBroccoli sprouts
Subjects (both healthy volunteers and subjects with cystic fibrosis) will consume 100 gm of raw broccoli sprouts once daily for 5 consecutive days.
Sponsors
Cystic Fibrosis Foundation
University Hospitals Cleveland Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Volunteers Healthy volunteers
Broccoli sprouts: Healthy volunteers will consume 100 gm of raw broccoli sprouts once daily for 5 consecutive days. | 10 |
| Subjects With Cystic Fibrosis Subjects with cystic fibrosis
Broccoli sprouts: Subjects with cystic fibrosis will consume 100 gm of raw broccoli sprouts once daily for 5 consecutive days. | 5 |
| Total | 15 |
Baseline characteristics
| Characteristic | Healthy Volunteers | Subjects With Cystic Fibrosis | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 5 Participants | 15 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 5 Participants | 15 Participants |
| Region of Enrollment United States | 10 participants | 5 participants | 15 participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 5 |
| other Total, other adverse events | 8 / 10 | 2 / 5 |
| serious Total, serious adverse events | 0 / 10 | 0 / 5 |
Outcome results
Primary
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)
Time frame: Baseline and of end of 5 day treatment period
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Healthy Volunteers | Nrf2 Activation in Nasal Epithelial Cells | Baseline | 0 participants |
| Healthy Volunteers | Nrf2 Activation in Nasal Epithelial Cells | Day 5, End of treatment | 4 participants |
| Subjects With Cystic Fibrosis | Nrf2 Activation in Nasal Epithelial Cells | Baseline | 0 participants |
| Subjects With Cystic Fibrosis | Nrf2 Activation in Nasal Epithelial Cells | Day 5, End of treatment | 4 participants |
Secondary
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.
Time frame: Baseline and end of 5 day treatment period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Volunteers | Measure of Neutrophil Migration Into the Gingival Crevices | -0.06 Neutrophils/mL (Log10) | Standard Deviation 0.14 |
| Subjects With Cystic Fibrosis | Measure of Neutrophil Migration Into the Gingival Crevices | -0.02 Neutrophils/mL (Log10) | Standard Deviation 0.04 |
Secondary
Measures of Glutathione From Blood Lymphocytes
Change in lymphocyte glutathione measurements after 5 days of study treatment (consuming broccoli sprouts).
Time frame: Baseline and end of 5 day treatment period
Population: Not enough blood could be obtained from one of the healthy volunteers. Therefore, glutathione from blood lymphocytes could not be evaluated from that healthy volunteer. With respect to this outcome measure, only results from 9 healthy volunteers are reported.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Volunteers | Measures of Glutathione From Blood Lymphocytes | 14.3 Micro Molar | Standard Deviation 25.9 |
| Subjects With Cystic Fibrosis | Measures of Glutathione From Blood Lymphocytes | 4.7 Micro Molar | Standard Deviation 48.1 |
Secondary
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)
Time frame: End of 5 day treatment period
Population: Data not collected and will not be analyzed.
Secondary
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).
Time frame: Baseline and end of 5 day treatment period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Volunteers | Measures of Oxidative Stress in Urine | 0.09 ng/mg creatinine (Log10) | Standard Deviation 0.23 |
| Subjects With Cystic Fibrosis | Measures of Oxidative Stress in Urine | 0.01 ng/mg creatinine (Log10) | Standard Deviation 0.33 |