The Potential for Oral Diindolylmethane (DIM) Supplementation to Increase the Production of the BRCA1 Protein in BRCA1 Mutation Carriers

The Potential for Oral DIM Supplementation to Increase the Production of the BRCA1 Protein in BRCA1 Mutation Carriers

Women with a BRCA1 mutation face a lifetime risk of breast cancer of approximately 70% and a lifetime risk of ovarian cancer of approximately 40%. A number of potential anti-cancer nutrients have been proposed, however, it is important that diet supplements be evaluated prior to general recommendation.

The risk of breast and ovarian cancer in carriers of a BRCA1 mutation might be lowered by some nutritional supplements. For example, green tea, broccoli and vitamin D are of potential interest. One dietary supplement that is thought to have potential for BRCA1 carriers is diindolylmethane (DIM), which is an active ingredient in broccoli and other green vegetables. DIM - is found in vegetables like broccoli and is available as a supplement in health food stores. The investigators think that DIM may increase the production of the normal copy of BRCA1 and offset the effect of the mutation.

The purpose of this study is to determine that there is a potential for oral DIM supplementation to result in the increased production of the BRCA1 protein in BRCA1 mutation carriers. The results of the study will also serve as an evaluation of the current use and success of preventive strategies for BRCA1 mutation carriers.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Dietary supplement: Diindolylmethane (DIM)

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1N8
      • Recruiting
      • Familial Breast Cancer Research Unit, Women's College Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Carriers of a mutation in the BRCA1 gene
• Non-carriers of a mutation in the BRCA1 gene who come from a family with a BRCA1 mutation (a family in which at least one individual has tested positive for a BRCA1 mutation)
• Can participate after being free of DIM supplementation for one month

Exclusion Criteria:

• Have a personal history of cancer
• Currently pregnant or breast-feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DIM group (BRCA1 carriers); This group will have up to 100 women who are carriers of a BRCA1 deleterious mutation. To ensure safety, women in this group will not be able to participate in the study if they are under medications with warfarin, theophylline, or anticonvulsants; or if they are pregnant, breast-feeding or planning to become pregnant within 6 months of the research project. Women in this group will receive 300 mg per day of Rx Balance BioResponse DIM for six weeks. Supplements will be given free of charge. A blood sample (20cc) and a urine sample (20cc) will be collected from these women during two clinic visits; the second visit will be during the six weeks of DIM supplementation (4-6 weeks after the first clinic visit).	Dietary supplement: Diindolylmethane (DIM); 300 mg per day of DIM for six weeks.; Other Names: Rx Balance BioResponse DIM
No Intervention: No DIM group (BRCA1 carriers); This group will have up to a 100 women who are carriers of a BRCA1 deleterious mutation. This group will not receive DIM. Women that choose not to take DIM will be in this group. A blood sample (20cc) and a urine sample (20cc) will be collected from these women during two clinic visits; the second visit will be 4-6 weeks after the first clinic visit.
No Intervention: General Control Group; This group will have up to 100 women who do not carry a BRCA1 mutation but who come from BRCA1 carrier family (a family with at least one individual that has tested positive for a BRCA1 mutation). A control subject is considered negative for a BRCA1 mutation if she has been confirmed by direct DNA sequencing to not be a carrier of this gene. A blood sample (20cc) and a urine sample (20cc) will be collected from these women at a single clinic visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Oral DIM supplementation increases BRCA1 mRNA expression and hence BRCA1 protein in women with a BRCA1 mutation	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Oral DIM supplementation causes favorable estrogen metabolism in women with a BRCA1 mutation	6 months

Collaborators and Investigators

• Sponsor: Women's College Hospital
• Collaborators: BioResponse
• Investigators: Principal Investigator: Steven A Narod, MD, Women's College Research Institute

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Anticipated): July 1, 2010
• Study Completion (Anticipated): December 1, 2010

Study Registration Dates

• First Submitted: November 26, 2009
• First Submitted That Met QC Criteria: November 30, 2009
• First Posted (Estimate): December 1, 2009

Study Record Updates

• Last Update Posted (Estimate): December 1, 2009
• Last Update Submitted That Met QC Criteria: November 30, 2009
• Last Verified: November 1, 2009

More Information

Terms related to this study

• Keywords: breast cancer; BRCA1; dietary intervention; Estrogen; 3,3'-di-indolylmethane; estrogen metabolites; mRNA expression; BRCA1 protein
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Protective Agents; Anticarcinogenic Agents; 3,3'-diindolylmethane
• Other Study ID Numbers: 2009-015-B