HealthyBroccOzNCT01625130
Effect of Sulforaphane-rich Broccoli Sprout Homogenate on Ozone Induced Inflammation Through Modulation of NRF2
A study testing Broccoli sprout homogenate and alfalfa sprout homogenate in people with Healthy, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
Purpose: To determine if modulation of NRF2 with a Sulforaphane enriched supplement modifies responses to O3. Participants: Recruitment of up to 70 healthy volunteers, ages 18-50, for completion of 36 volunteers. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Broccoli sprout homogenate and alfalfa sprout homogenate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2013to Jun 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Normal lung function, defined as (NHanes 2001 set):
- FVC of > 80 % of that predicted for gender, ethnicity, age and height; FEV1 of > 80 % of that predicted for gender, ethnicity, age and height; FEV1/FVC ratio of > .70.
- Negative pregnancy test for females who are not s/p hysterectomy with oophorectomy;
- Willing to avoid corticosteroids and non-steroidal anti-inflammatory medications for 1 week prior the baseline screening visit and again for 1 week prior to all remaining visits;
- Willing to avoid antioxidant vitamins and cruciferous vegetables as well as juices/drinks with added vitamin supplements for 7 days prior the baseline screening visit and throughout initial dosing period and ozone challenge as well as 7 days prior to the start of the 2nd dosing period and subsequent challenge.
- Willing to abstain from caffeine for 12 hours prior to all visits.Inclusion Criteria:
- -
Who cannot join
- Any chronic medical condition considered by the PI as a contraindication to the exposure study including, but not limited to, asthma, significant cardiovascular disease, diabetes, chronic renal or thyroid disease;
- Use of tricyclics and MAO inhibitors;
- Pregnancy or nursing a baby;
- Any current smoking;
- Viral upper respiratory tract infection within 2 weeks of challenge;
- Any acute infection requiring antibiotics within 2 weeks of challenge;
Show all 17Show fewer
- Abnormal physical findings at the baseline visit:
- Abnormalities on lung auscultation Temperature > 37.8 Systolic BP>150 mm hg or < 85 mm Hg or diastolic BP>90 mm Hg or < 50 Oxygen saturation of < 94%;
- Subjects must demonstrate the ability to produce an acceptable induced sputum sample during the screening session. If the sample is unsatisfactory, the subject's participation will end at that point;
- Subjects who have been prescribed daily anti-inflammatory medications or medications for asthma will be excluded. Oral contraceptives are acceptable. Antidepressants and other medications may be permitted if in the opinion of the investigator the medication will not interfere with the study procedures or compromise safety; and if the dosage has been stable for 1 month;
- Subjects who are unwilling to refrain from strenuous physical activity for 24 hours before and after exposure;
- Current nutritional disorder such as anorexia, bulimia, irritable bowel syndrome, Crohn's disease etc;
- Current use of immunosuppressive drugs;
- History of intolerance of or aversion to broccoli;
- Inability or unwillingness of a participant to give written informed consent;
- Receipt of LAIV (Live Attenuated Influenza Vaccine), also known as FluMist®, or other live vaccine within the prior 14 days.
- Orthopedic injuries or impediments that would preclude treadmill exercise.
Trial locations and contacts
1 site in 1 country.
United States1 site
UNC Center for Environmental Medicine, Asthma and Lung Biology
Chapel Hill, North Carolina, 27599-7310
About this study
Official title: Down Regulation of Oxidant Induced Airway Inflammation Through Modulation of NRF2
Purpose: To determine if modulation of NRF2 with a Sulforaphane enriched supplement modifies responses to O3. Participants: Recruitment of up to 70 healthy volunteers, ages 18-50, for completion of 36 volunteers. Procedures: This is a randomized, placebo controlled 2x2 crossover study of treatment with an NRF2 modifier versus placebo in healthy volunteers which will examine airway inflammation before and 4 hours after a 2 hour 0.4 ppm O3 exposure. Participants will be randomized to received either the NRF2 modifier, SFN oral supplement (i.e. broccoli sprout shake), or placebo (alfalfa shake) for 3 days followed by a 0.4 ppm O3 exposure for 2 hours. At least 2 weeks later subjects will return for a 2nd supplementation treatment (using the alternative supplement to that provided initially) followed by an ozone exposure identical to the initial one.
Read the detailed description
Potential subjects will be seen for a baseline screening visit at which time informed consent will be obtained, a 12 lead ECG will be performed and spirometry with subsequent sputum induction will be performed. Only subjects meeting the lung function criteria as well as criteria for adequate sputum production will continue in the study. If the sample is considered "borderline" by the study team, the subject maybe invited back to repeat collection of another sputum sample. Subjects will be required to abstain from caffeine for 12 hours prior to all study visits and must not use/ingest non-steroidal anti-inflammatory medications, anti-oxidant vitamins, juices/drinks fortified with extra vitamin supplement and cruciferous vegetables 7 days prior to all visits. Subjects will be provided with a list of cruciferous vegetables.
Qualified volunteers will next be seen for a training visit at which time they will undergo physical exam by a study physician. After baseline spirometry is evaluated, the subject will exercise on a treadmill, and measurements of minute ventilation will be collected. Treadmill speed and/or elevation will be adjusted until the subject's minute ventilation is at the target level of 30-40 L/min. The resulting speed and elevation will be used during the ozone exposure sessions. At the training visit, participants will also undergo nasal epithelial biopsy from one nare, and a buccal swab will be collected for genotyping. Baseline blood samples will also be collected at this time for analyses of markers of inflammation, cytokine assessments, SFN levels and complete blood cell count with differential.
After completion of the training session, the subject will return for 4 sequential days. During the first 3 days, subjects will ingest (observed ingestion) either broccoli sprout homogenate or alfalfa sprout homogenate based on earlier randomization. One hour after the supplement dose on the 3rd day, the volunteer will undergo exposure to 0.4 ppm ozone for a 2 hour period. During exposure, subjects will perform 15 minutes of moderate exercise on a treadmill (minute ventilation = 30-40 L/min), each separated by 15 minutes of seated rest. Heart rate and rhythm will be continuously monitored throughout the exposure. Spirometry and symptom scoring will be performed both prior to and after exposure. One hour after the end of exposure, a nasal epithelial biopsy will be collected from the nare that is contralateral to that used at the prior visit. Four hours after completion of the exposure, blood will be drawn for study endpoints and a sputum induction will be performed. The following day the subject will return for a follow-up visit to include vital signs, symptom scoring, spirometry, sputum induction and venipuncture for blood endpoints.
Subjects will be required to abstain from a list of vegetables for 1 week prior to each study session until the completion of that session. Subjects will also be asked to maintain a food diary for the same time.
After a 2 to 6 weeks washout period, participants will again return for a repeated sequence of 4 days with 3 days of supplement ingestion followed by ozone exposure using the alternate supplement and a 24 hour post exposure follow-up visit. Samples for analyses will be collected at the same time points as those used in the initial sequence.
- Conditions
- Healthy
- Being tested
- Broccoli sprout homogenate, alfalfa sprout homogenate
- Keywords
- sulforaphane, ozone, airway inflammation, broccoli sprouts, NRF2, controls
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Broccoli sprout homogenateDietary supplement
Also called Broccosprouts® (Brassica Protection Products LLC)
Commercially available Broccosprouts® (Brassica Protection Products LLC) will be homogenized with water using a ratio of 1:1.2 in a clean blender. The homogenate will then be frozen in aliquots at -20 degrees C.
alfalfa sprout homogenateDietary supplement
200 grams of alfalfa sprouts will be homogenized with water using a ratio of 1:1.2 in a clean blender. The homogenate will then be frozen in aliquots at -20 degrees C.
| Study group | Role | What they receive |
|---|---|---|
| broccoli sprout homogenate (BSH) | Active comparator | Two hundred grams of BSH is equivalent to approximately 111 grams fresh sprouts (about one 4 oz package). Commercially available Broccosprouts® (Brassica Protection Products LLC) will be homogenized with water. Receives: Dietary Supplement: Broccoli sprout homogenate |
| alfalfa sprout homogenate | Placebo comparator | Two hundred grams of commercially available alfalfa sprouts will be homogenized with water using a ratio of 1:1.2 in a clean blender. The homogenate will then be frozen in aliquots at -20 degrees C. Receives: Dietary Supplement: alfalfa sprout homogenate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in % neutrophils in induced sputum, comparing the 4 hr post O3 placebo v. SFN treatment periods.
Induced sputum will be collected and % neutrophils will be measured after each exposure and will be compared to baseline and to each other.
Measured: baseline, 4 and 24 hours post exposure
Secondary outcomes (4)
Spirometry (FEV1, FVC, FEF25-75) for assessment of changes in lung function
Lung function testing will be performed prior to, after and 24 hours post exposure
Measured: prior to and after exposures
SFN levels
Sulforaphane levels will be measured in blood and sputum at predetermined intervals
Measured: at baseline (sputum & plasma); immediately before the O3 exposure (plasma), 4 hours & 24 hours post O3 (sputum & plasma).
Cytokine concentration and flow cytometric assessment of surface markers in sputum supernatants
GM-CSF, IL-1β, IL-6, IL-8, IL-10, IL-12p70, TNF-α, PGE2
Measured: baseline, 4 and 24 hours post exposure
mRNA expression of NRF2 and phase II antioxidant enzymes in nasal epithelial cells and in induced sputum macrophages
GSTM1, GSTP1, NQO1, and HO1)
Measured: baseline and 1 hour (nasal epithelial cells only) 4 and 24 hours post exposure (sputum)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2012 (estimated)
- Study startOct 2013
- Primary completionMay 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Environmental Protection Agency (EPA)
- Responsible party
- Principal investigator, Michelle Hernandez, MD, University of North Carolina, Chapel Hill
- Investigators
- Michelle Hernandez, Principal investigator, University of North Carolina, Chapel Hill School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01625130
- Sponsor's protocol ID
- 11-1296
- Acronym
- BroccOz
- Status last verified
- Jun 2015
- First submitted
- 19 Jun 2012
- Last updated
- 11 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Duran CG, Burbank AJ, Mills KH, Duckworth HR, Aleman MM, Kesic MJ, Peden DB, Pan Y, Zhou H, Hernandez ML. A proof-of-concept clinical study examining the NRF2 activator sulforaphane against neutrophilic airway inflammation. Respir Res. 2016 Jul 22;17(1):89. doi: 10.1186/s12931-016-0406-8.
PubMed 27450419
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Down Regulation of Oxidant Induced Airway Inflammation Through Modulation of NRF2
- ClinicalTrials.gov ID
- NCT01625130
- Acronym / sponsor ID
- BroccOz / 11-1296
- Conditions
- Healthy
- Keywords
- sulforaphane, ozone, airway inflammation, broccoli sprouts, NRF2, controls
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Environmental Protection Agency (EPA)
- Study start
- Oct 2013
- Primary completion
- May 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 21 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Purpose: To determine if modulation of NRF2 with a Sulforaphane enriched supplement modifies responses to O3. Participants: Recruitment of up to 70 healthy volunteers, ages 18-50, for completion of 36 volunteers. Procedures: This is a randomized, placebo controlled 2x2 crossover study of treatment with an NRF2 modifier versus placebo in healthy volunteers which will examine airway inflammation before and 4 hours after a 2 hour 0.4 ppm O3 exposure. Participants will be randomized to received either the NRF2 modifier, SFN oral supplement (i.e. broccoli sprout shake), or placebo (alfalfa shake) for 3 days followed by a 0.4 ppm O3 exposure for 2 hours. At least 2 weeks later subjects will return for a 2nd supplementation treatment (using the alternative supplement to that provided initially) followed by an ozone exposure identical to the initial one.
Detailed description
Potential subjects will be seen for a baseline screening visit at which time informed consent will be obtained, a 12 lead ECG will be performed and spirometry with subsequent sputum induction will be performed. Only subjects meeting the lung function criteria as well as criteria for adequate sputum production will continue in the study. If the sample is considered "borderline" by the study team, the subject maybe invited back to repeat collection of another sputum sample. Subjects will be required to abstain from caffeine for 12 hours prior to all study visits and must not use/ingest non-steroidal anti-inflammatory medications, anti-oxidant vitamins, juices/drinks fortified with extra vitamin supplement and cruciferous vegetables 7 days prior to all visits. Subjects will be provided with a list of cruciferous vegetables.
Qualified volunteers will next be seen for a training visit at which time they will undergo physical exam by a study physician. After baseline spirometry is evaluated, the subject will exercise on a treadmill, and measurements of minute ventilation will be collected. Treadmill speed and/or elevation will be adjusted until the subject's minute ventilation is at the target level of 30-40 L/min. The resulting speed and elevation will be used during the ozone exposure sessions. At the training visit, participants will also undergo nasal epithelial biopsy from one nare, and a buccal swab will be collected for genotyping. Baseline blood samples will also be collected at this time for analyses of markers of inflammation, cytokine assessments, SFN levels and complete blood cell count with differential.
After completion of the training session, the subject will return for 4 sequential days. During the first 3 days, subjects will ingest (observed ingestion) either broccoli sprout homogenate or alfalfa sprout homogenate based on earlier randomization. One hour after the supplement dose on the 3rd day, the volunteer will undergo exposure to 0.4 ppm ozone for a 2 hour period. During exposure, subjects will perform 15 minutes of moderate exercise on a treadmill (minute ventilation = 30-40 L/min), each separated by 15 minutes of seated rest. Heart rate and rhythm will be continuously monitored throughout the exposure. Spirometry and symptom scoring will be performed both prior to and after exposure. One hour after the end of exposure, a nasal epithelial biopsy will be collected from the nare that is contralateral to that used at the prior visit. Four hours after completion of the exposure, blood will be drawn for study endpoints and a sputum induction will be performed. The following day the subject will return for a follow-up visit to include vital signs, symptom scoring, spirometry, sputum induction and venipuncture for blood endpoints.
Subjects will be required to abstain from a list of vegetables for 1 week prior to each study session until the completion of that session. Subjects will also be asked to maintain a food diary for the same time.
After a 2 to 6 weeks washout period, participants will again return for a repeated sequence of 4 days with 3 days of supplement ingestion followed by ozone exposure using the alternate supplement and a 24 hour post exposure follow-up visit. Samples for analyses will be collected at the same time points as those used in the initial sequence.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| broccoli sprout homogenate (BSH) | Active comparator | Dietary Supplement: Broccoli sprout homogenateTwo hundred grams of BSH is equivalent to approximately 111 grams fresh sprouts (about one 4 oz package). Commercially available Broccosprouts® (Brassica Protection Products LLC) will be homogenized with water. |
| alfalfa sprout homogenate | Placebo comparator | Dietary Supplement: alfalfa sprout homogenateTwo hundred grams of commercially available alfalfa sprouts will be homogenized with water using a ratio of 1:1.2 in a clean blender. The homogenate will then be frozen in aliquots at -20 degrees C. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Normal lung function, defined as (NHanes 2001 set):
- FVC of > 80 % of that predicted for gender, ethnicity, age and height; FEV1 of > 80 % of that predicted for gender, ethnicity, age and height; FEV1/FVC ratio of > .70.
- Negative pregnancy test for females who are not s/p hysterectomy with oophorectomy;
- Willing to avoid corticosteroids and non-steroidal anti-inflammatory medications for 1 week prior the baseline screening visit and again for 1 week prior to all remaining visits;
- Willing to avoid antioxidant vitamins and cruciferous vegetables as well as juices/drinks with added vitamin supplements for 7 days prior the baseline screening visit and throughout initial dosing period and ozone challenge as well as 7 days prior to the start of the 2nd dosing period and subsequent challenge.
Key exclusion criteria (17 listed)
- Any chronic medical condition considered by the PI as a contraindication to the exposure study including, but not limited to, asthma, significant cardiovascular disease, diabetes, chronic renal or thyroid disease;
- Use of tricyclics and MAO inhibitors;
- Pregnancy or nursing a baby;
- Any current smoking;
- Viral upper respiratory tract infection within 2 weeks of challenge;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Broccoli sprout homogenateAlso: Broccosprouts® (Brassica Protection Products LLC)Commercially available Broccosprouts® (Brassica Protection Products LLC) will be homogenized with water using a ratio of 1:1.2 in a clean blender. The homogenate will then be frozen in aliquots at -20 degrees C. | Dietary supplement | broccoli sprout homogenate (BSH) |
| alfalfa sprout homogenate200 grams of alfalfa sprouts will be homogenized with water using a ratio of 1:1.2 in a clean blender. The homogenate will then be frozen in aliquots at -20 degrees C. | Dietary supplement | alfalfa sprout homogenate |
Primary outcome
Change in % neutrophils in induced sputum, comparing the 4 hr post O3 placebo v. SFN treatment periods.
Time frame: baseline, 4 and 24 hours post exposure
Induced sputum will be collected and % neutrophils will be measured after each exposure and will be compared to baseline and to each other.
4 secondary outcomes
Spirometry (FEV1, FVC, FEF25-75) for assessment of changes in lung function
Time frame: prior to and after exposures
SFN levels
Time frame: at baseline (sputum & plasma); immediately before the O3 exposure (plasma), 4 hours & 24 hours post O3 (sputum & plasma).
Cytokine concentration and flow cytometric assessment of surface markers in sputum supernatants
Time frame: baseline, 4 and 24 hours post exposure
mRNA expression of NRF2 and phase II antioxidant enzymes in nasal epithelial cells and in induced sputum macrophages
Time frame: baseline and 1 hour (nasal epithelial cells only) 4 and 24 hours post exposure (sputum)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2015.
- Derived from this study: PubMed 27450419Duran CG, Burbank AJ, Mills KH, Duckworth HR, Aleman MM, Kesic MJ, Peden DB, Pan Y, Zhou H, Hernandez ML. A proof-of-concept clinical study examining the NRF2 activator sulforaphane against neutrophilic airway inflammation. Respir Res. 2016 Jul 22;17(1):89. doi: 10.1186/s12931-016-0406-8.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michelle Hernandez principal investigator
University of North Carolina, Chapel Hill School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Broccoli sprout homogenate and alfalfa sprout homogenate in people with Healthy, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in % neutrophils in induced sputum, comparing the 4 hr post O3 placebo v. SFN treatment periods. (time frame: baseline, 4 and 24 hours post exposure). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01625130, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2015.