NCT01315665

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
15

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Apr 2011

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 14, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

March 15, 2011

Completed
17 days until next milestone

Study Start

First participant enrolled

April 1, 2011

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2013

Completed
4 years until next milestone

Results Posted

Study results publicly available

February 15, 2017

Completed
Last Updated

February 15, 2019

Status Verified

January 1, 2019

Enrollment Period

1.8 years

First QC Date

March 14, 2011

Results QC Date

December 6, 2016

Last Update Submit

January 29, 2019

Conditions

Cystic Fibrosis

Keywords

broccoli sproutssulforaphanetriterpenoidNrf2 activationcystic fibrosishealthy volunteersanti-inflammatory

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (4)

  • Measures of Lipid Peroxidation in Nasal Epithelial Cells

    End of 5 day treatment period

  • Measures of Glutathione From Blood Lymphocytes

    Baseline and end of 5 day treatment period

  • Measures of Oxidative Stress in Urine

    Baseline and end of 5 day treatment period

  • Measure of Neutrophil Migration Into the Gingival Crevices

    Baseline and end of 5 day treatment period

Study Arms (2)

Healthy volunteers

EXPERIMENTAL

100 grams of raw broccoli sprouts once daily for 5 consecutive days

Dietary Supplement: Broccoli sprouts

Subjects with cystic fibrosis

EXPERIMENTAL

100 grams of raw broccoli sprouts once daily for 5 consecutive days

Dietary Supplement: Broccoli sprouts

Interventions

Broccoli sproutsDIETARY_SUPPLEMENT

Subjects (both healthy volunteers and subjects with cystic fibrosis) will consume 100 gm of raw broccoli sprouts once daily for 5 consecutive days.

Also known as: sulforaphane
Healthy volunteersSubjects with cystic fibrosis

Eligibility Criteria

Age18 Years - 49 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Related Publications (19)

  • Chmiel JF, Berger M, Konstan MW. The role of inflammation in the pathophysiology of CF lung disease. Clin Rev Allergy Immunol. 2002 Aug;23(1):5-27. doi: 10.1385/CRIAI:23:1:005.

    PMID: 12162106BACKGROUND

  • Chen J, Kinter M, Shank S, Cotton C, Kelley TJ, Ziady AG. Dysfunction of Nrf-2 in CF epithelia leads to excess intracellular H2O2 and inflammatory cytokine production. PLoS One. 2008;3(10):e3367. doi: 10.1371/journal.pone.0003367. Epub 2008 Oct 10.

    PMID: 18846238BACKGROUND

  • Nichols DP, Ziady AG, Shank SL, Eastman JF, Davis PB. The triterpenoid CDDO limits inflammation in preclinical models of cystic fibrosis lung disease. Am J Physiol Lung Cell Mol Physiol. 2009 Nov;297(5):L828-36. doi: 10.1152/ajplung.00171.2009. Epub 2009 Aug 21.

    PMID: 19700644BACKGROUND

  • Verhaeghe C, Remouchamps C, Hennuy B, Vanderplasschen A, Chariot A, Tabruyn SP, Oury C, Bours V. Role of IKK and ERK pathways in intrinsic inflammation of cystic fibrosis airways. Biochem Pharmacol. 2007 Jun 15;73(12):1982-94. doi: 10.1016/j.bcp.2007.03.019. Epub 2007 Mar 24.

    PMID: 17466952BACKGROUND

  • Li J, Johnson XD, Iazvovskaia S, Tan A, Lin A, Hershenson MB. Signaling intermediates required for NF-kappa B activation and IL-8 expression in CF bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2003 Feb;284(2):L307-15. doi: 10.1152/ajplung.00086.2002. Epub 2002 Sep 27.

    PMID: 12388360BACKGROUND

  • Escotte S, Tabary O, Dusser D, Majer-Teboul C, Puchelle E, Jacquot J. Fluticasone reduces IL-6 and IL-8 production of cystic fibrosis bronchial epithelial cells via IKK-beta kinase pathway. Eur Respir J. 2003 Apr;21(4):574-81. doi: 10.1183/09031936.03.00031803.

    PMID: 12762338BACKGROUND

  • Lands LC, Stanojevic S. Oral non-steroidal anti-inflammatory drug therapy for cystic fibrosis. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD001505. doi: 10.1002/14651858.CD001505.pub2.

    PMID: 17943753BACKGROUND

  • Flume PA, O'Sullivan BP, Robinson KA, Goss CH, Mogayzel PJ Jr, Willey-Courand DB, Bujan J, Finder J, Lester M, Quittell L, Rosenblatt R, Vender RL, Hazle L, Sabadosa K, Marshall B; Cystic Fibrosis Foundation, Pulmonary Therapies Committee. Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health. Am J Respir Crit Care Med. 2007 Nov 15;176(10):957-69. doi: 10.1164/rccm.200705-664OC. Epub 2007 Aug 29.

    PMID: 17761616BACKGROUND

  • Oermann CM, Sockrider MM, Konstan MW. The use of anti-inflammatory medications in cystic fibrosis: trends and physician attitudes. Chest. 1999 Apr;115(4):1053-8. doi: 10.1378/chest.115.4.1053.

    PMID: 10208207BACKGROUND

  • Konstan MW. Ibuprofen therapy for cystic fibrosis lung disease: revisited. Curr Opin Pulm Med. 2008 Nov;14(6):567-73. doi: 10.1097/MCP.0b013e32831311e8.

    PMID: 18812834BACKGROUND

  • Shishodia S, Sethi G, Konopleva M, Andreeff M, Aggarwal BB. A synthetic triterpenoid, CDDO-Me, inhibits IkappaBalpha kinase and enhances apoptosis induced by TNF and chemotherapeutic agents through down-regulation of expression of nuclear factor kappaB-regulated gene products in human leukemic cells. Clin Cancer Res. 2006 Mar 15;12(6):1828-38. doi: 10.1158/1078-0432.CCR-05-2044.

    PMID: 16551868BACKGROUND

  • Ahmad R, Raina D, Meyer C, Kharbanda S, Kufe D. Triterpenoid CDDO-Me blocks the NF-kappaB pathway by direct inhibition of IKKbeta on Cys-179. J Biol Chem. 2006 Nov 24;281(47):35764-9. doi: 10.1074/jbc.M607160200. Epub 2006 Sep 24.

    PMID: 16998237BACKGROUND

  • Dinkova-Kostova AT, Liby KT, Stephenson KK, Holtzclaw WD, Gao X, Suh N, Williams C, Risingsong R, Honda T, Gribble GW, Sporn MB, Talalay P. Extremely potent triterpenoid inducers of the phase 2 response: correlations of protection against oxidant and inflammatory stress. Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4584-9. doi: 10.1073/pnas.0500815102. Epub 2005 Mar 14.

    PMID: 15767573BACKGROUND

  • Liby K, Hock T, Yore MM, Suh N, Place AE, Risingsong R, Williams CR, Royce DB, Honda T, Honda Y, Gribble GW, Hill-Kapturczak N, Agarwal A, Sporn MB. The synthetic triterpenoids, CDDO and CDDO-imidazolide, are potent inducers of heme oxygenase-1 and Nrf2/ARE signaling. Cancer Res. 2005 Jun 1;65(11):4789-98. doi: 10.1158/0008-5472.CAN-04-4539.

    PMID: 15930299BACKGROUND

  • Yates MS, Tauchi M, Katsuoka F, Flanders KC, Liby KT, Honda T, Gribble GW, Johnson DA, Johnson JA, Burton NC, Guilarte TR, Yamamoto M, Sporn MB, Kensler TW. Pharmacodynamic characterization of chemopreventive triterpenoids as exceptionally potent inducers of Nrf2-regulated genes. Mol Cancer Ther. 2007 Jan;6(1):154-62. doi: 10.1158/1535-7163.MCT-06-0516.

    PMID: 17237276BACKGROUND

  • Konstan MW, Byard PJ, Hoppel CL, Davis PB. Effect of high-dose ibuprofen in patients with cystic fibrosis. N Engl J Med. 1995 Mar 30;332(13):848-54. doi: 10.1056/NEJM199503303321303.

    PMID: 7503838BACKGROUND

  • Konstan MW, Schluchter MD, Xue W, Davis PB. Clinical use of Ibuprofen is associated with slower FEV1 decline in children with cystic fibrosis. Am J Respir Crit Care Med. 2007 Dec 1;176(11):1084-9. doi: 10.1164/rccm.200702-181OC. Epub 2007 Sep 13.

    PMID: 17872492BACKGROUND

  • Chmiel JF, Konstan MW. Inflammation and anti-inflammatory therapies for cystic fibrosis. Clin Chest Med. 2007 Jun;28(2):331-46. doi: 10.1016/j.ccm.2007.02.002.

    PMID: 17467552BACKGROUND

  • Konstan MW, Krenicky JE, Finney MR, Kirchner HL, Hilliard KA, Hilliard JB, Davis PB, Hoppel CL. Effect of ibuprofen on neutrophil migration in vivo in cystic fibrosis and healthy subjects. J Pharmacol Exp Ther. 2003 Sep;306(3):1086-91. doi: 10.1124/jpet.103.052449. Epub 2003 Jun 13.

    PMID: 12807998BACKGROUND

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

sulforaphane

Condition Hierarchy (Ancestors)

Pancreatic DiseasesDigestive System DiseasesLung DiseasesRespiratory Tract DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesInfant, Newborn, Diseases

Results Point of Contact

Title
James Chmiel
Organization
Riley Hospital for Children
jfchmiel@iu.edu
317-948-7180

Study Officials

  • James F. Chmiel, MD, MPH

    Rainbow Babies and Children's Hospital

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor of Pediatrics

Study Record Dates

First Submitted

March 14, 2011

First Posted

March 15, 2011

Study Start

April 1, 2011

Primary Completion

February 1, 2013

Study Completion

February 1, 2013

Last Updated

February 15, 2019

Results First Posted

February 15, 2017

Record last verified: 2019-01

Locations

US(1)