Overview

This trial is active, not recruiting.

Condition copd
Treatments sulforaphane 25, sulforaphane 150, placebo
Phase phase 2
Sponsor Johns Hopkins University
Collaborator Temple University
Start date September 2010
End date July 2013
Trial size 90 participants
Trial identifier NCT01335971, 1U01HL105569, NCT01318603, RFA-HL-10-003

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Active Comparator)
25 micromoles (4.4 mg) sulforaphane daily by mouth
sulforaphane 25 This is derived from broccoli sprouts.
25 micromoles (4.4 mg) sulforaphane daily by mouth
(Active Comparator)
150 micromoles (26.6 mg) sulforaphane daily by mouth
sulforaphane 150
150 micromoles (26.6 mg) sulforaphane daily by mouth
(Placebo Comparator)
Microcrystalline cellulose
placebo
Microcrystalline cellulose once daily by mouth

Primary Outcomes

Measure
Change from baseline in Nrf2 expression at 4 weeks
time frame: Baseline and 4 weeks

Secondary Outcomes

Measure
Change from baseline in isoprostane at 4 weeks
time frame: Baseline and 4 weeks

Eligibility Criteria

Male or female participants at least 40 years old.

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

Additional Information

Official title Enhancing Nrf2 by Sulforaphane Treatment in COPD
Principal investigator Janet T Holbrook, PhD, MPH
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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2014.
Information provided to ClinicalTrials.gov by Johns Hopkins University.