Broccoli Sprout Extracts Trial (BEST)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Temple University
State University of New York at Buffalo
Information provided by (Responsible Party):
Robert A. Wise, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01335971
First received: April 8, 2011
Last updated: March 19, 2014
Last verified: March 2014
  Purpose

Evidence from investigators' group has shown that chronic obstructive pulmonary disease (COPD) patients have impairment of antioxidant defenses which are caused by a defect in activity of Nrf2. This trial focuses on sulforaphane, a derivative of cruciferous vegetables, which is a potent stimulator of Nrf2 activity. The investigators want to investigate whether ingestion of sulforaphane by COPD patients will increase Nrf2 activity and expression of downstream antioxidants. Accordingly, the investigators are conducting a placebo-controlled randomized proof of principle trial of two oral doses of sulforaphane, 25 and 150 micromoles, for 4 weeks in 90 COPD patients. The investigators' goal is to establish a safe and tolerable dose of sulforaphane that effects in vivo antioxidants via Nrf2, then the investigators will have a novel candidate treatment for longer-term efficacy trials.


Condition Intervention Phase
COPD
Drug: Sulforaphane 25
Dietary Supplement: Sulforaphane 150
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Enhancing Nrf2 by Sulforaphane Treatment in COPD

Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Change from baseline in Nrf2 expression at 4 weeks [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: No ]
    The primary design variable is the change from baseline in Nrf2 expression in alveolar macrophages (AM)/bronchial epithelial cells (BEC) at 4 weeks by analysing Nrf2 protein, expression of a panel of Nrf2 regulated genes, Glutathione (GSH) levels and proteasomal activity.


Secondary Outcome Measures:
  • Change from baseline in isoprostane at 4 weeks [ Time Frame: Baseline and 4 weeks ] [ Designated as safety issue: Yes ]
    Oxidant stress indicators (isoprostane) will be measured in plasma and expired breath at baseline and 4 weeks.


Estimated Enrollment: 90
Study Start Date: September 2010
Estimated Study Completion Date: June 2014
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Sulforaphane 25
25 micromoles (4.4 mg) sulforaphane daily by mouth
Drug: Sulforaphane 25
25 micromoles (4.4 mg) sulforaphane daily by mouth
Other Name: This is derived from broccoli sprouts.
Active Comparator: Sulforaphane 150
150 micromoles (26.6 mg) sulforaphane daily by mouth
Dietary Supplement: Sulforaphane 150
150 micromoles (26.6 mg) sulforaphane daily by mouth
Placebo Comparator: Placebo
Microcrystalline cellulose
Other: Placebo
Microcrystalline cellulose once daily by mouth

Detailed Description:

Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality in the United States and is a growing cause of chronic disease internationally. Presently, there are limited treatment options for this disease to modify the progression of airflow obstruction and decrease periodic exacerbations. Recent evidence has emphasized the central role of oxidative stress as a mechanism of COPD pathobiology. Evidence from investigators' group has shown that COPD patients and animals exposed to cigarette smoke have impairment of antioxidant defenses which are caused by a defect in activity of Nrf2, a prolific regulator of anti-oxidant enzymes, glutathione homeostasis, and cytoprotective proteins. Activation of Nrf2 protects mice with chronic smoke exposure from developing emphysema, decreases oxidative stress, increases proteasomal anti-apoptotic cytoprotective responses, improves bacterial phagocytosis and killing, and reverses tobacco-smoke induced corticosteroid resistance. Similarly, in vitro Nrf2 activation in human COPD lung cells has shown improved cytoprotection, improved bacterial clearance, and restoration of steroid sensitivity. This trial focuses on sulforaphane, a derivative of cruciferous vegetables, which is a potent in vitro and in vivo stimulator of Nrf2 activity. The investigators want to investigate whether ingestion of sulforaphane by chronic obstructive pulmonary disease (COPD) patients will increase Nrf2 activity and expression of downstream antioxidants in alveolar macrophages and bronchial epithelial cells. Accordingly, the investigators are conducting a placebo-controlled randomized proof of principle trial of two oral doses of sulforaphane, 25 and 150 micromoles, for 4 weeks in 90 COPD patients. Collections of alveolar macrophages by Bronchoalveolar lavage (BAL), bronchial epithelial cells by endobronchial brushings will be performed at baseline and 4 weeks. Other bio-specimens will include nasal epithelial cells, Peripheral Blood Monocyte Collection (PBMCs), and expired breath condensate (EBC). The investigators' goal is to establish a safe and tolerable dose of sulforaphane that effects in vivo antioxidants via Nrf2, then the investigators will have a novel candidate treatment for longer-term efficacy trials. Ancillary studies are proposed to explore the efficacy and mechanisms of sulforaphane to increase bacterial clearance and to restore steroid sensitivity in COPD lung cells.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 40 years or greater, either sex
  2. 10 or more pack-years smoking history
  3. Physician diagnosed COPD
  4. Post bronchodilator Forced expiratory volume in 1 second (FEV1)/ forced expiratory vital capacity (FVC) ratio < 0.70
  5. FEV1 40-80 % predicted
  6. Willingness to ingest no more than 1 serving of cruciferous vegetables per week during run-in and treatment periods
  7. Ability and willingness to provide informed consent

Exclusion Criteria:

  1. COPD exacerbation within preceding 6 weeks requiring treatment
  2. Significant respiratory (other than COPD), cardiovascular, neuropsychiatric, renal, gastrointestinal, or genitourinary disease that would interfere with participation in the study or interpretation of the results.
  3. Acute Myocardial infarction (MI) or Acute Coronary syndrome within 6 prior months
  4. Cancer (other than skin or localized prostate) within preceding 5 years
  5. Child-bearing potential with lack of adequate contraception, Pregnancy or lactation. Acceptable forms of birth control include abstinence, hysterectomy, tubal ligation, two of the following: vasectomy, condom, diaphragm, intrauterine device, oral or implanted contraceptives, or spermicide.
  6. Allergy to local anesthesia
  7. Resting hypoxemia (O2 saturation < 90%)
  8. Glomerular Filtration Rate (GFR) < 30
  9. Liver enzymes four times upper normal
  10. Current use of warfarin for any indication
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01335971

Locations
United States, Maryland
Johns Hopkins School of Medicine
Baltimore, Maryland, United States, 21224
United States, New York
University at Baffalo, The State University of New York
Buffalo, New York, United States, 14215
United States, Pennsylvania
Temple University
Philadelphia, Pennsylvania, United States, 19122
Sponsors and Collaborators
Johns Hopkins University
Temple University
State University of New York at Buffalo
Investigators
Principal Investigator: Janet T Holbrook, PhD, MPH Johns Hopkins Bloomberg School of Public Health
  More Information

No publications provided

Responsible Party: Robert A. Wise, Professor of Medicine, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01335971     History of Changes
Obsolete Identifiers: NCT01318603
Other Study ID Numbers: 1U01HL105569, RFA-HL-10-003
Study First Received: April 8, 2011
Last Updated: March 19, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Johns Hopkins University:
COPD
Nrf2
Sulforaphane

Additional relevant MeSH terms:
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Diseases
Sulforafan
Anticarcinogenic Agents
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 31, 2014