Effect of Sulforaphane-rich Broccoli Sprout Homogenate on Ozone Induced Inflammation Through Modulation of NRF2

NCT01625130 | Completed

• 1 other identifier: 11-1296
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Healthy

Keywords

sulforaphane; ozone; airway inflammation; broccoli sprouts; NRF2; controls

Outcome Measures

Primary Outcomes (1)

• 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.

  baseline, 4 and 24 hours post exposure

Secondary Outcomes (4)

• Spirometry (FEV1, FVC, FEF25-75) for assessment of changes in lung function

  prior to and after exposures

• SFN levels

  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

  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

  baseline and 1 hour (nasal epithelial cells only) 4 and 24 hours post exposure (sputum)

Study Arms (2)

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.

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.

Dietary Supplement: alfalfa sprout homogenate

Interventions

Broccoli sprout homogenate DIETARY_SUPPLEMENT

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.

Also known as: Broccosprouts® (Brassica Protection Products LLC)

broccoli sprout homogenate (BSH)

alfalfa sprout homogenate DIETARY_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.

alfalfa sprout homogenate

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Environmental Protection Agency (EPA): collaborator

Study Sites (1)

UNC Center for Environmental Medicine, Asthma and Lung Biology

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

Location

Related Publications (1)

• 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.

  PMID: 27450419 DERIVED

Study Officials

• Michelle Hernandez

  University of North Carolina, Chapel Hill School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: June 19, 2012
• First Posted: June 21, 2012
• Study Start: October 1, 2013
• Primary Completion: May 1, 2015
• Study Completion: June 1, 2015
• Last Updated: June 11, 2015

Record last verified: 2015-06

Locations

US (1)