Broccoli Supplement Dose Response

Do daily high (4 tablets) or intermediate (2 tablets) administration of the broccoli-based dietary supplement Avmacol® have improved bioavailability over a broccoli sprout beverage rich in sulforaphane and its biogenic precursor, glucoraphanin? The beverage formulation has been used successfully in the investigators' previous intervention studies in regions of China with high levels of air pollution to reduce the body burden of carcinogenic and toxic pollutants. The investigators seek to evaluate a more stable, less expensive formulation of a broccoli sprout preparation that can be used for disease prevention in future studies.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Dietary supplement: Placebo tablets; Dietary supplement: Avmacol tablets

Detailed Description

The investigators will conduct a 3-armed placebo-controlled 16-day intervention with the dietary supplement Avmacol® to determine the bioavailability with repeated dosing of a simple tablet-based intervention in the study participants. As shown in Scheme 1, the 3 arms are: 1) 4 tablets of Avmacol® daily for 14 days; 2) 2 tablets of Avmacol® daily for 14 days together with 2 placebo tablets to maintain parity in consumption; and 3) 4 placebo tablets daily for 14 days. In addition, all participants will receive 4 placebo tablets for 2 consecutive run-in days prior to commencing intervention in the 3 distinct arms. Consecutive overnight (12-hour) urine samples will be collected during the 2-day run-in, the 14-day intervention and during a 5-day run-out period (total = 21 days). Additional day-time urine collections will be made at 2 timepoints: the day after administration of Avmacol® tablets begins and the day after the last administration of Avmacol® tablets. A blood sample will be collected at the beginning of the run-in and after the last Avmacol® dose (Day 17 for intervention groups, and for the placebo group) from each participant. The tablets will be taken before dinner each day.

• Study Type: Interventional
• Enrollment (Actual): 170
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Qidong, Jiangsu, China, 226200
      • Qidong Liver Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 21 and ≤ 70 years who are residents of Qidong, China.
2. Able to provide written, informed consent.
3. Normal physical examination and medical history indicative of good general health with no history of chronic illness.
4. No hepatomegaly by clinical exam;
5. Normal liver function tests (ALT, aspartate aminotransferase (AST), bilirubin);
6. Normal renal function tests (creatinine, blood urea nitrogen (BUN), urinalysis);
7. Serum alpha-fetoprotein (AFP) negative.

Exclusion Criteria:

1. Pregnant (positive human chorionic gonadotropin (HCG) strip test)
2. Current or former diagnosis of cancer, with the exception of non-melanomatous skin cancer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 4 placebo tablets	Dietary supplement: Placebo tablets; MCC 90M Emcocel
Active Comparator: Low Dose Avmacol; 2 tablets Avmacol and 2 placebo tablets	Dietary supplement: Placebo tablets; MCC 90M Emcocel; Dietary supplement: Avmacol tablets; The active components of Avmacol® are ground broccoli seeds that provide glucoraphanin and freeze-dried broccoli sprouts that provide a stabilized form of the enzyme myrosinase, which converts glucoraphanin to sulforaphane.
Active Comparator: High Dose Avmacol; 4 Avmacol tablets	Dietary supplement: Avmacol tablets; The active components of Avmacol® are ground broccoli seeds that provide glucoraphanin and freeze-dried broccoli sprouts that provide a stabilized form of the enzyme myrosinase, which converts glucoraphanin to sulforaphane.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Excretion of sulforaphane and metabolites in urine	Levels of sulforaphane and its glutathione-conjugate derived metabolites will be measured in consecutive overnight urine samples	Consecutive overnight urine samples collected for the duration of the study (21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Air pollution biomarkers in urine	Levels of benzene mercapturic acid excreted in urine	Consecutive overnight urine samples collected for the duration of the study (21 days)

Collaborators and Investigators

• Sponsor: Johns Hopkins Bloomberg School of Public Health
• Collaborators: Qidong Liver Cancer Institute
• Investigators: Principal Investigator: Thomas W Kensler, PhD, Johns Hopkins Bloomberg School of Public Health

Publications and helpful links

General Publications

• Egner PA, Chen JG, Zarth AT, Ng DK, Wang JB, Kensler KH, Jacobson LP, Munoz A, Johnson JL, Groopman JD, Fahey JW, Talalay P, Zhu J, Chen TY, Qian GS, Carmella SG, Hecht SS, Kensler TW. Rapid and sustainable detoxication of airborne pollutants by broccoli sprout beverage: results of a randomized clinical trial in China. Cancer Prev Res (Phila). 2014 Aug;7(8):813-823. doi: 10.1158/1940-6207.CAPR-14-0103. Epub 2014 Jun 9.

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2018
• Primary Completion (Actual): February 15, 2018
• Study Completion (Actual): February 15, 2018

Study Registration Dates

• First Submitted: January 8, 2018
• First Submitted That Met QC Criteria: January 8, 2018
• First Posted (Actual): January 16, 2018

Study Record Updates

• Last Update Posted (Actual): October 4, 2022
• Last Update Submitted That Met QC Criteria: October 3, 2022
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: IRB00008184

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Individual participant data (IPD) that underlie results in a publication
• IPD Sharing Time Frame: Upon completion of biomarker analyses (January 2020)
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No