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

NCT01335971 | Completed Phase 2 Results DMC

• 2 other identifiers: 1U01HL105569RFA-HL-10-003
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

COPD

Keywords

COPD; Nrf2; Sulforaphane

Outcome Measures

Primary Outcomes (6)

• Change From Baseline in Alveolar Macrophage Expression of Nrf2 and Associated Genes at 4 Weeks

  The first primary design variable is the change from baseline in nuclear factor erythroid 2 like 2 (Nrf2) expression in alveolar macrophages (AM) at 4 weeks by analysing Nrf2 protein and expression of a panel of Nrf2 regulated genes.Three participants - one from each treatment group - were unable to complete follow-up bronchoalveolar lavage for primary outcome data.

  Baseline and 4 weeks

• Change From Baseline in Bronchial Epithelial Cell Expression of Nrf2 at 4 Weeks

  The second primary design variable is the change from baseline in nuclear factor erythroid 2 like 2 (Nrf2) expression in bronchial epithelial cells (BEC) at 4 weeks by analysing Nrf2 protein. Three participants - one from each treatment group - were unable to complete follow-up bronchoalveolar lavage for primary outcome data.

  Baseline and 4 weeks

• Change From Baseline in Bronchial Epithelial Cell Expression of NQ01 and Keap1 at 4 Weeks

  The third primary design variable is the change from baseline in NAD(P)H Quinone Dehydrogenase 1 (NQ01) and Kelch Like ECH Associated Protein 1 (Keap1) expression in bronchial epithelial cells (BEC) at 4 weeks. Three participants - one from each treatment group - were unable to complete follow-up bronchoalveolar lavage for primary outcome data.

  Baseline and 4 weeks

• Change From Baseline in Bronchial Epithelial Cell Expression of HO1 at 4 Weeks

  The fourth primary design variable is the change from baseline in expression of Heme Oxygenase 1 (HO1) in bronchial epithelial cells (BEC) at 4 weeks. Three participants - one from each treatment group - were unable to complete follow-up bronchoalveolar lavage for primary outcome data.

  Baseline and 4 weeks

• Change From Baseline in Bronchial Epithelial Cell Expression of AKR1C1 at 4 Weeks

  The fifth primary design variable is the change from baseline in expression of Aldo-Keto Reductase Family 1 Member C1 (AKR1C1) in bronchial epithelial cells (BEC) at 4 weeks. Three participants - one from each treatment group - were unable to complete follow-up bronchoalveolar lavage for primary outcome data.

  Baseline and 4 weeks

• Change From Baseline in Bronchial Epithelial Cell Expression of AKR1C3 at 4 Weeks

  The sixth primary design variable is the change from baseline in expression of Aldo-Keto Reductase Family 1 Member C3 (AKR1C3) in bronchial epithelial cells (BEC) at 4 weeks. Three participants - one from each treatment group - were unable to complete follow-up bronchoalveolar lavage for primary outcome data.

  Baseline and 4 weeks

Secondary Outcomes (4)

• Fold-change in Isoprostane Concentrations (Follow-up to Baseline)

  Baseline and 4 weeks

• Fold-change in Serum Inflammatory Marker Concentrations (Follow-up to Baseline)

  Baseline and 4 weeks

• Fold-change in Inflammatory Marker Concentrations in Bronchial Alveolar Lavage (Follow-up to Baseline) by Treatment Group

  Baseline and 4 weeks

• Fold-change in Plasma Inflammatory Marker Concentrations (Follow-up to Baseline)

  Baseline and 4 weeks

Study Arms (3)

Sulforaphane 25

ACTIVE COMPARATOR

25 micromoles (4.4 mg) sulforaphane daily by mouth

Drug: Sulforaphane 25

Sulforaphane 150

ACTIVE COMPARATOR

150 micromoles (26.6 mg) sulforaphane daily by mouth

Dietary Supplement: Sulforaphane 150

Placebo

PLACEBO COMPARATOR

Microcrystalline cellulose

Other: Placebo

Interventions

Sulforaphane 25 DRUG

25 micromoles (4.4 mg) sulforaphane daily by mouth

Also known as: This is derived from broccoli sprouts.

Sulforaphane 25

Sulforaphane 150 DIETARY_SUPPLEMENT

150 micromoles (26.6 mg) sulforaphane daily by mouth

Sulforaphane 150

Placebo OTHER

Microcrystalline cellulose once daily by mouth

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 40 years or greater, either sex
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• Temple University: collaborator
• State University of New York at Buffalo: collaborator

Study Sites (3)

Johns Hopkins School of Medicine

Baltimore, Maryland, 21224, United States

Location

University at Baffalo, The State University of New York

Buffalo, New York, 14215, United States

Location

Temple University

Philadelphia, Pennsylvania, 19122, United States

Location

Related Publications (2)

• Sidhaye VK, Holbrook JT, Burke A, Sudini KR, Sethi S, Criner GJ, Fahey JW, Berenson CS, Jacobs MR, Thimmulappa R, Wise RA, Biswal S. Compartmentalization of anti-oxidant and anti-inflammatory gene expression in current and former smokers with COPD. Respir Res. 2019 Aug 20;20(1):190. doi: 10.1186/s12931-019-1164-1.

  PMID: 31429757 DERIVED

• Wise RA, Holbrook JT, Criner G, Sethi S, Rayapudi S, Sudini KR, Sugar EA, Burke A, Thimmulappa R, Singh A, Talalay P, Fahey JW, Berenson CS, Jacobs MR, Biswal S; Broccoli Sprout Extract Trial Research Group. Lack of Effect of Oral Sulforaphane Administration on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial. PLoS One. 2016 Nov 10;11(11):e0163716. doi: 10.1371/journal.pone.0163716. eCollection 2016.

  PMID: 27832073 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Alexis Rea
• Organization: Johns Hopkins University School of Medicine

area5@jhu.edu

(443) 287-8496

Study Officials

• Janet T Holbrook, PhD, MPH

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2011
• First Posted: April 15, 2011
• Study Start: September 1, 2010
• Primary Completion: July 1, 2013
• Study Completion: June 1, 2015
• Last Updated: May 19, 2017
• Results First Posted: May 19, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will share

Locations

US (3)