Broccoli, Peas and PIN

• ClinicalTrials.gov Identifier: NCT00535977
• Recruitment Status: Completed
• First Posted: September 27, 2007
• Last Update Posted: September 27, 2007
• Sponsor: Quadram Institute Bioscience
• Information provided by: Quadram Institute Bioscience

Study Description

Brief Summary:

This is a parallel human intervention trial to determine to what extent a dietary intervention of broccoli or peas can change the expression (switching on or off) of genes in prostate tissue in men diagnosed with high-grade Prostate Intraepithelial Neoplasia (PIN).

Condition or disease	Intervention/treatment	Phase
Prostatic Intraepithelial Neoplasia	Dietary Supplement: Broccoli; Dietary Supplement: Peas	Not Applicable

Detailed Description:

Cancer is one of the main causes of death among humans in the world. Prostate cancer affects 20,000 men in the UK alone each year. Diet is known to be a major factor that influences risk of cancer. Therefore, changes to the diet may alter cancer risk. Cruciferous vegetables, particularly broccoli, provide the diet with a substantial source of plant chemicals called glucosinolates. Previous research has indicated that glucosinolates break down to form isothiocyanates (ITCs) that can be absorbed in the body. Further research has indicated that ITCs may protect the body against the development of prostate cancer. However, the mechanisms behind this effect are not fully understood.

ITCs are thought to be powerful anti cancer agents as they can modulate the expression (switching on or off) of specific genes involved in the removal of toxic substances such as carcinogens from the body. In this study we wish to evaluate the effect of consumption of a conventionally bred cultivar of broccoli containing high levels of ITCs on gene expression in prostate tissue to gain a better understanding of its mechanism of action. Several studies suggest a further protection against cancer amongst individuals who have a deletion of certain genes.

This pilot study comprises a 12-month intervention of either 400g ITC-enriched broccoli per week of 400g garden peas in men at high risk of developing prostate cancer. Changes in gene expression of prostate biopsy tissue will be compared before and after 6 and 12 months of intervention in both dietary groups.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Human Intervention Trial Studying Gene Expression in High-Grade Prostatic Intraepithelial Neoplasia Following Consumption of Broccoli or Peas
• Study Start Date: April 2005
• Actual Study Completion Date: April 2007

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; Dietary intervention of ITC-enriched broccoli	Dietary Supplement: Broccoli; 400g ITC-enriched broccoli per week for 12 months
Experimental: 2; Dietary intervention of frozen peas	Dietary Supplement: Peas; 400g frozen garden peas per week for 12 months

Outcome Measures

Primary Outcome Measures :

1. Changes in gene expression in RNA extracted from prostate tissue [ Time Frame: Baseline, 6 months and 12 months ]

Secondary Outcome Measures :

1. Changes in levels of serum prostate specific antigen (PSA) [ Time Frame: Baseline, 6 months and 12 months ]

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Men with a previous diagnosis of high-grade Prostatic Intraepithelial Neoplasia
• BMI >18.5 or <35
• Aged between 30-70 years

Exclusion Criteria:

• Undergoing chemopreventive therapy
• Receiving testosterone replacement medicines
• Active infection requiring treatment
• BMI <18.5 or >35
• Diagnosed with diabetes
• Unable to give informed consent

Contacts and Locations

Sponsors and Collaborators

Quadram Institute Bioscience

Investigators

• Principal Investigator: Richard F Mithen, PhD; Institute of Food Research, Norwich

More Information

Publications:

Chiao JW, Chung FL, Kancherla R, Ahmed T, Mittelman A, Conaway CC. Sulforaphane and its metabolite mediate growth arrest and apoptosis in human prostate cancer cells. Int J Oncol. 2002 Mar;20(3):631-6. doi: 10.3892/ijo.20.3.631.

Cotton SC, Sharp L, Little J, Brockton N. Glutathione S-transferase polymorphisms and colorectal cancer: a HuGE review. Am J Epidemiol. 2000 Jan 1;151(1):7-32. doi: 10.1093/oxfordjournals.aje.a010124.

Fenwick GR, Heaney RK, Mullin WJ. Glucosinolates and their breakdown products in food and food plants. Crit Rev Food Sci Nutr. 1983;18(2):123-201. doi: 10.1080/10408398209527361. No abstract available.

Gamet-Payrastre L, Li P, Lumeau S, Cassar G, Dupont MA, Chevolleau S, Gasc N, Tulliez J, Terce F. Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells. Cancer Res. 2000 Mar 1;60(5):1426-33.

Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC. A prospective study of cruciferous vegetables and prostate cancer. Cancer Epidemiol Biomarkers Prev. 2003 Dec;12(12):1403-9.

Hecht SS. Inhibition of carcinogenesis by isothiocyanates. Drug Metab Rev. 2000 Aug-Nov;32(3-4):395-411. doi: 10.1081/dmr-100102342.

Hintze KJ, Keck AS, Finley JW, Jeffery EH. Induction of hepatic thioredoxin reductase activity by sulforaphane, both in Hepa1c1c7 cells and in male Fisher 344 rats. J Nutr Biochem. 2003 Mar;14(3):173-179. doi: 10.1016/s0955-2863(02)00282-6.

Key TJ, Silcocks PB, Davey GK, Appleby PN, Bishop DT. A case-control study of diet and prostate cancer. Br J Cancer. 1997;76(5):678-87. doi: 10.1038/bjc.1997.445.

Mithen R, Faulkner K, Magrath R, Rose P, Williamson G, Marquez J. Development of isothiocyanate-enriched broccoli, and its enhanced ability to induce phase 2 detoxification enzymes in mammalian cells. Theor Appl Genet. 2003 Feb;106(4):727-34. doi: 10.1007/s00122-002-1123-x. Epub 2002 Oct 24.

Surh YJ. Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer. 2003 Oct;3(10):768-80. doi: 10.1038/nrc1189.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Traka M, Gasper AV, Melchini A, Bacon JR, Needs PW, Frost V, Chantry A, Jones AM, Ortori CA, Barrett DA, Ball RY, Mills RD, Mithen RF. Broccoli consumption interacts with GSTM1 to perturb oncogenic signalling pathways in the prostate. PLoS One. 2008 Jul 2;3(7):e2568. doi: 10.1371/journal.pone.0002568.

• ClinicalTrials.gov Identifier: NCT00535977
• Other Study ID Numbers: IFR07-2004; 05/Q0101/9; 2004IFR04
• First Posted: September 27, 2007
• Last Update Posted: September 27, 2007
• Last Verified: September 2007

Keywords provided by Quadram Institute Bioscience:

Gene expression; Prostate; Broccoli; Cancer; Men diagnosed with high-grade Prostatic Intraepithelia Neoplasia

Additional relevant MeSH terms:

Neoplasms; Carcinoma in Situ; Prostatic Intraepithelial Neoplasia; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type