Broccoli Sprout Extracts Trial

COPD Clinical Trial

— BEST  

Official title:

Enhancing Nrf2 by Sulforaphane Treatment in COPD

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01335971
• Other study ID #: 1U01HL105569
• Secondary ID: RFA-HL-10-003
• Status: Active, not recruiting
• Phase: Phase 2
• First received: April 8, 2011
• Last updated: March 19, 2014
• Start date: September 2010
• Est. completion date: June 2014

Study information

• Verified date: March 2014
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT01318603

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 90
• Est. completion date: June 2014
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• COPD

Intervention

Drug:
• Sulforaphane 25
25 micromoles (4.4 mg) sulforaphane daily by mouth

Dietary Supplement:
• Sulforaphane 150
150 micromoles (26.6 mg) sulforaphane daily by mouth

Other:
• Placebo
Microcrystalline cellulose once daily by mouth

Locations

Country	Name	City	State
United States	Johns Hopkins School of Medicine	Baltimore	Maryland
United States	University at Baffalo, The State University of New York	Buffalo	New York
United States	Temple University	Philadelphia	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Johns Hopkins University	State University of New York at Buffalo, Temple University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in Nrf2 expression at 4 weeks	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.	Baseline and 4 weeks	No
Secondary	Change from baseline in isoprostane at 4 weeks	Oxidant stress indicators (isoprostane) will be measured in plasma and expired breath at baseline and 4 weeks.	Baseline and 4 weeks	Yes