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

Tracking Information

• First Submitted Date: September 26, 2007
• First Posted Date: September 27, 2007
• Last Update Posted Date: September 27, 2007
• Study Start Date: April 2005
• Primary Completion Date: Not Provided
• Current Primary Outcome Measures (submitted: September 26, 2007): Changes in gene expression in RNA extracted from prostate tissue [ Time Frame: Baseline, 6 months and 12 months ]
• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted
• Current Secondary Outcome Measures (submitted: September 26, 2007): Changes in levels of serum prostate specific antigen (PSA) [ Time Frame: Baseline, 6 months and 12 months ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Broccoli, Peas and PIN
• Official Title: A Human Intervention Trial Studying Gene Expression in High-Grade Prostatic Intraepithelial Neoplasia Following Consumption of Broccoli or Peas
• 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).

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 Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Prostatic Intraepithelial Neoplasia

Intervention

• Dietary Supplement: Broccoli
  400g ITC-enriched broccoli per week for 12 months
• Dietary Supplement: Peas
  400g frozen garden peas per week for 12 months

Study Arms

• Experimental: 1
  Dietary intervention of ITC-enriched broccoli
  Intervention: Dietary Supplement: Broccoli
• Experimental: 2
  Dietary intervention of frozen peas
  Intervention: Dietary Supplement: Peas

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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 26, 2007): 22
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: April 2007
• Primary Completion Date: Not Provided

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 30 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT00535977
• Other Study ID Numbers: IFR07-2004; 05/Q0101/9; 2004IFR04
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Not Provided
• Original Responsible Party: Same as current
• Current Study Sponsor: Quadram Institute Bioscience
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Quadram Institute Bioscience
• Verification Date: September 2007