Phase 2 N=89 Randomized Quadruple-blind Treatment

Broccoli Sprout Extracts Trial to See if NRF2 is Enhanced by Sulforaphane Treatment in Patients With COPD

COPD

Bottom Line

View on ClinicalTrials.gov: NCT01335971 ↗

Enrolled (actual)

Serious AEs

3.4%

Results posted

May 2017

Primary outcome: Primary: Change From Baseline in Alveolar Macrophage Expression of Nrf2 and Associated Genes at 4 Weeks — 0.80; 1.03; 0.94; 0.90 fold change — p=0.45

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Sulforaphane 25 (Drug); Sulforaphane 150 (Dietary_supplement); Placebo (Other)
Age: Adult, Older Adult · 40+ yrs
Sex: All
Sponsor: Johns Hopkins University
Primary completion: Jul 2013

Outcome Measures

Outcome	Result	p-value
PRIMARY Change From Baseline in Alveolar Macrophage Expression of Nrf2 and Associated Genes at 4 Weeks	0.80; 1.03; 0.94; 0.90; 0.98; 1.06	0.45
PRIMARY Change From Baseline in Bronchial Epithelial Cell Expression of Nrf2 at 4 Weeks	1.09; 1.06; 1.06	0.68
PRIMARY Change From Baseline in Bronchial Epithelial Cell Expression of NQ01 and Keap1 at 4 Weeks	1.09; 1.12; 0.96; 1.12; 1.39; 0.87	0.69
PRIMARY Change From Baseline in Bronchial Epithelial Cell Expression of HO1 at 4 Weeks	1.05; 1.12; 0.93	0.53
PRIMARY Change From Baseline in Bronchial Epithelial Cell Expression of AKR1C1 at 4 Weeks	1.45; 1.08; 0.79	<0.01 sig
PRIMARY Change From Baseline in Bronchial Epithelial Cell Expression of AKR1C3 at 4 Weeks	1.10; 1.38; 0.87	0.06
SECONDARY Fold-change in Isoprostane Concentrations (Follow-up to Baseline)	1.18; 0.83; 0.64	0.20
SECONDARY Fold-change in Serum Inflammatory Marker Concentrations (Follow-up to Baseline)	0.99; 0.90; 1.01; 0.75; 0.90; 1.12	0.41
SECONDARY Fold-change in Inflammatory Marker Concentrations in Bronchial Alveolar Lavage (Follow-up to Baseline) by Treatment Group	1.22; 0.94; 1.11; 1.51; 1.09; 1.12	0.71
SECONDARY Fold-change in Plasma Inflammatory Marker Concentrations (Follow-up to Baseline)	0.89; 0.90; 0.88; 0.96; 1.05; 1.06	0.80

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.

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

COPD exacerbation within preceding 6 weeks requiring treatment
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.
Acute Myocardial infarction (MI) or Acute Coronary syndrome within 6 prior months
Cancer (other than skin or localized prostate) within preceding 5 years
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.
Allergy to local anesthesia
Resting hypoxemia (O2 saturation < 90%)
Glomerular Filtration Rate (GFR) < 30
Liver enzymes four times upper normal
Current use of warfarin for any indication

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01335971). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.