Study to Evaluate the Effect of Sulforaphane in Broccoli Sprout Extract on Breast Tissue

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT00982319
• Collaborator: Breast Cancer Research Foundation (Other)
• Enrollment: 34
• Location: 1
• Arms: 2
• Duration (Months): 55
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this research is to examine the effect of a broccoli sprout preparation on specific factors in breast tissue that are related to breast cancer risk and to assess whether sulforaphane a key component of broccoli sprouts increases the levels of protective enzymes in breast tissue. In addition, the investigators will also examine how acceptable the broccoli sprouts preparation is to the study participants.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Broccoli sprout extract; Drug: Mango juice	Phase 2

Detailed Description

A double-blind randomized Phase II chemoprevention trial of BSE versus placebo will be conducted in up to 35 women diagnosed with DCIS on core biopsy prior to their definitive surgery (study diagram below). The primary study endpoint will be a decrease in the mean proliferative rate measured by Ki67%.

Women diagnosed with DCIS on core or incisional/excisional biopsy scheduled for definitive surgery at Johns Hopkins Hospital will be recruited for this study. Participants will be placed on a cruciferous free diet for the 14 days prior to their surgical date and drink a randomized intervention beverage (mango juice with or without broccoli sprout extract). Additionally participants will provide 2 blood and 2 urine sample collections, report medication use and adverse events using prepared forms and complete a daily diet check list during the 14 day intervention. On the day of definitive breast surgery, 1-2 grams of breast tissue (including normal adjacent breast tissue) will be collected during surgery.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Evaluating the Effect of Broccoli Sprouts (Sulforaphane) on Cellular Proliferation, an Intermediate Marker of Breast Cancer Risk
• Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Broccoli sprout extract Patients will be randomized to 14 day intervention of broccoli sprout extract and mango juice consisting of a dose of 100 µmols of sulforaphane dissolved in 150 mL mango juice once a day.	Drug: Broccoli sprout extract; 100 µmols of sulforaphane (dissolvable); Drug: Mango juice; 150 mL of mango juice
Placebo Comparator: Mango juice Patients will be randomized to 14 day intervention of 150 mL mango juice without broccoli sprout extract extract once a day.	Drug: Mango juice; 150 mL of mango juice

Outcome Measures

Primary Outcome Measures

1. Absolute Change in Mean Proliferative Rate Measured by Ki67% [Change from baseline to 14 days post-intervention]

   Pathologists score the slides without knowledge of treatment assignment at the end of the study. All pre-post samples from one individual will be evaluated together. Quality control for these stains is performed routinely in the immunohistochemistry lab (using lymphoid tissue for Ki67). Initial scoring is performed where possible on a minimum of 3000 cells, by counting the number of positive cells divided by the total number of cells. DCIS lesions will be scored separately to adjacent normal tissue. The rationale for selecting Ki67 as a measure of cellular proliferation includes the robustness of the staining reaction, correlation with the S phase fraction of the cell cycle and mitotic index and that it can be successfully ascertained from core breast biopsies provided there is an adequate yield of epithelial cells. A negative value reflects a decrease in ki67 positive cells, therefore a decrease in cellular proliferation.

Secondary Outcome Measures

1. Phase II Protein Expression as Assessed by Change in Cytoprotective Enzyme Expression Within Tumor [Change from baseline to 14 days post-intervention]

   Phase II protein expression of cytoprotective enzymes known to be modulated by sulforaphane in DCIS specimens. Cytoprotective enzymes measured (NQ01 and AKR1C1 expression) based on immunohistochemical analysis. Expression was categorized by the study pathologist based on percentage of cells expressing antibody on the slide.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Female 18 + years of age

• Confirmed diagnosis of DCIS on core or excisional/incisional biopsy and scheduled for definitive surgery

• Pre or Post menopausal women reporting no use of hormone replacement therapy, tamoxifen or raloxifene within the prior 6 months to eligibility screening

• Agree to avoid cruciferous vegetable/condiment intake for 14 days

• Agree to sign an informed consent and allow use of some tissue (slides) from biopsy and definitive surgery for research purposes

Exclusion Criteria:

• Prior cancer diagnosis other than non-melanomatous skin cancer or cervical carcinoma in-situ

• Used hormone replacement therapy, tamoxifen or raloxifene within the past 6 months prior to eligibility screening

• Used antibiotics within 10 days prior to beginning cruciferous free diet (day -14 prior to surgery)

• Smoked within the past 12 months prior to eligibility screening;

• Active infection or inflammation of the breast at time of eligibility screening

• Has baseline comprehensive metabolic panel (CMP) [Glucose, Calcium, Albumin, Serum total protein (TP), Sodium, Potassium, Carbon dioxide, Chloride, Blood urea nitrogen (BUN), Creatinine, Alkaline phosphatase (ALP), Alanine amino transferase (AST), Aspartate amino transferase (SGOT), and Bilirubin], prothrombin time (PT) and , complete blood count (CBC) values that are 1.5 times in either direction the reported normal range

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins Medical Institution	Baltimore	Maryland	United States	21205

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Breast Cancer Research Foundation

Investigators

• Principal Investigator: Kala Visvanathan, MD, Johns Hopkins Bloomberg School of Public Health and Sidney Kimmel Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT00982319
• Other Study ID Numbers: J0822
• First Posted: Sep 23, 2009
• Last Update Posted: Nov 21, 2018
• Last Verified: Nov 1, 2018

• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: Broccoli Sprout Extract; Breast Cancer
• Additional relevant MeSH terms: Breast Neoplasms

Study Results

Participant Flow

Arm/Group Title	Broccoli Sprout Extract and Mango Juice	Mango Juice
Arm/Group Description	Patients will be randomized to 14 day intervention of broccoli sprout extract consisting of a consistent dose of sulforaphane dissolved in mango juice compared to a placebo preparation of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days). Broccoli sprout extract (sulforaphane): Women newly diagnosed with DCIS on core biopsy prior to definitive surgery will be randomized to receive a prepartion of broccoli sprout extract and mango juice. All women will be on a cruciferous free diet for the duration of the study (14 days) and complete a daily dietary check list. Twelve hour urine collections and blood samples will be collected at various time points during the study. Acceptability of the 14 day dose will be evaluated by monitoring indices of compliance, including urinary measurements of ITC excretion, the daily food check list and a questionnaire administered at the end of the study.	Patients will be randomized to 14 day intervention of mango juice without broccoli sprout extract. All women will be on a cruciferous free diet for the duration of the study (14 days).Mango juice without extract: Mango juice without broccoli sprout extract. B Mango juice: Women newly diagnosed with DCIS on core biopsy prior to definitive surgery will be randomized to receive a placebo preparation of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days) and complete a daily dietary check list. Twelve hour urine collections and blood samples will be collected at various time points during the study. Acceptability of the 14 day dose will be evaluated by monitoring indices of compliance, including urinary measurements of ITC excretion, the daily food check list and a questionnaire administered at the end of the study.
Period Title: Overall Study
STARTED	17	17
COMPLETED	15	15
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Broccoli Sprout Extract and Mango Juice	Mango Juice	Total
Arm/Group Description	Patients will be randomized to 14 day intervention of broccoli sprout extract consisting of a consistent dose of sulforaphane dissolved in mango juice compared to a placebo preparation of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days). Broccoli sprout extract (sulforaphane): Women newly diagnosed with DCIS on core biopsy prior to definitive surgery will be randomized to either a prepartion of broccoli sprout extract and mango juice or a placebo preparation of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days) and complete a daily dietary check list. Twelve hour urine collections and blood samples will be collected at various time points during the study. Acceptability of the 14 day dose will be evaluated by monitoring indices of compliance, including urinary measurements of ITC excretion, the daily food check list and a questionnaire administered at the end of the study.	Patients will be randomized to 14 day intervention of Mango juice without broccoli extract. All women will be on a cruciferous free diet for the duration of the study (14 days). Mango juice: Women newly diagnosed with DCIS on core biopsy prior to definitive surgery will be randomized to either a prepartion of broccoli sprout extract and mango juice or a placebo preparation of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days) and complete a daily dietary check list. Twelve hour urine collections and blood samples will be collected at various time points during the study. Acceptability of the 14 day dose will be evaluated by monitoring indices of compliance, including urinary measurements of ITC excretion, the daily food check list and a questionnaire administered at the end of the study.	Total of all reporting groups
Overall Participants	15	15	30
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	13 86.7%	12 80%	25 83.3%
>=65 years	2 13.3%	3 20%	5 16.7%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	52	54	53
Sex: Female, Male (Count of Participants)
Female	15 100%	15 100%	30 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	15 100%	15 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	Absolute Change in Mean Proliferative Rate Measured by Ki67%
Description	Pathologists score the slides without knowledge of treatment assignment at the end of the study. All pre-post samples from one individual will be evaluated together. Quality control for these stains is performed routinely in the immunohistochemistry lab (using lymphoid tissue for Ki67). Initial scoring is performed where possible on a minimum of 3000 cells, by counting the number of positive cells divided by the total number of cells. DCIS lesions will be scored separately to adjacent normal tissue. The rationale for selecting Ki67 as a measure of cellular proliferation includes the robustness of the staining reaction, correlation with the S phase fraction of the cell cycle and mitotic index and that it can be successfully ascertained from core breast biopsies provided there is an adequate yield of epithelial cells. A negative value reflects a decrease in ki67 positive cells, therefore a decrease in cellular proliferation.
Time Frame	Change from baseline to 14 days post-intervention

Outcome Measure Data

Analysis Population Description

All participants who completed the 14-day intervention on either study arm were included in analysis.

Arm/Group Title	Broccoli Sprout Extract and Mango Juice	Mango Juice Without Extract
Arm/Group Description	Patients will be randomized to 14 day intervention of broccoli sprout extract consisting of a consistent dose of sulforaphane dissolved in mango juice. All women will be on a cruciferous free diet for the duration of the study (14 days).	Patients will be randomized to 14 day intervention of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days).
Measure Participants	15	15
Mean (Standard Deviation) [percentage of Ki67]	-1.15 (2.08)	4 (17.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Broccoli Sprout Extract and Mango Juice, Mango Juice Without Extract
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.32
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Phase II Protein Expression as Assessed by Change in Cytoprotective Enzyme Expression Within Tumor
Description	Phase II protein expression of cytoprotective enzymes known to be modulated by sulforaphane in DCIS specimens. Cytoprotective enzymes measured (NQ01 and AKR1C1 expression) based on immunohistochemical analysis. Expression was categorized by the study pathologist based on percentage of cells expressing antibody on the slide.
Time Frame	Change from baseline to 14 days post-intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Broccoli Sprout Extract and Mango Juice	Mango Juice Without Extract
Arm/Group Description	Patients will be randomized to 14 day intervention of broccoli sprout extract consisting of a consistent dose of sulforaphane dissolved in mango juice. All women will be on a cruciferous free diet for the duration of the study (14 days).	Patients will be randomized to 14 day intervention of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days).
Measure Participants	15	15
AKR1C1	62.1 (312.99)	867.4 (2097.8)
NQO1	730.98 (2411.96)	6.34 (30.12)

Adverse Events

Time Frame	14 days during the intervention period (prior to first and 3 times during intervention)
Arm/Group Title	Broccoli Sprout Extract and Mango Juice		Mango Juice
Arm/Group Description	Patients will be randomized to 14 day intervention of broccoli sprout extract consisting of a consistent dose of sulforaphane dissolved in mango juice compared to a placebo preparation of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days). Broccoli sprout extract (sulforaphane): Women newly diagnosed with DCIS on core biopsy prior to definitive surgery will be randomized to either a prepartion of broccoli sprout extract and mango juice or a placebo preparation of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days) and complete a daily dietary check list. Twelve hour urine collections and blood samples will be collected at various time points during the study. Acceptability of the 14 day dose will be evaluated by monitoring indices of compliance, including urinary measurements of ITC excretion, the daily food check list and a questionnaire administered at the end of the study.		Patients will be randomized to 14 day intervention of Mango juice without broccoli extract. All women will be on a cruciferous free diet for the duration of the study (14 days). Mango juice: Women newly diagnosed with DCIS on core biopsy prior to definitive surgery will be randomized to either a prepartion of broccoli sprout extract and mango juice or a placebo preparation of mango juice alone. All women will be on a cruciferous free diet for the duration of the study (14 days) and complete a daily dietary check list. Twelve hour urine collections and blood samples will be collected at various time points during the study. Acceptability of the 14 day dose will be evaluated by monitoring indices of compliance, including urinary measurements of ITC excretion, the daily food check list and a questionnaire administered at the end of the study.
All Cause Mortality
	Broccoli Sprout Extract and Mango Juice		Mango Juice
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Serious Adverse Events
	Broccoli Sprout Extract and Mango Juice		Mango Juice
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Broccoli Sprout Extract and Mango Juice		Mango Juice
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/15 (60%)		9/15 (60%)
Gastrointestinal disorders
constipation	5/15 (33.3%)	9	4/15 (26.7%)	7
intestional gas/bloating	4/15 (26.7%)	6	2/15 (13.3%)	6
upset stomach/indigestion	1/15 (6.7%)	1	1/15 (6.7%)	1
nausea/vomiting	1/15 (6.7%)	2	0/15 (0%)	0
abdominal cramps	0/15 (0%)	0	2/15 (13.3%)	2
diarrhea	1/15 (6.7%)	1	0/15 (0%)	0
appetite/ taste alteration	2/15 (13.3%)	2	1/15 (6.7%)	1
Nervous system disorders
light headed/ mild anxiety	1/15 (6.7%)	1	1/15 (6.7%)	1

Limitations/Caveats

Eligible patients had to have their definitive breast cancer surgery at Johns Hopkins Hospital

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.