Clinical trial NCT00049309: Low-Fat Diet and/or Flaxseed in Preventing Prostate Cancer
Official title: Prostate Cancer: Impact Of Fat And Flaxseed - Modified Diets
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: stage I prostate cancer
stage IIB prostate cancer
stage IIA prostate cancer
stage III prostate cancer
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 161
Sex: MALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: A diet that is low in fat and/or high in flaxseed may slow or prevent disease progression of prostate cancer.

PURPOSE: Randomized phase II trial to study the effectiveness of a diet that is low in fat and/or high in flaxseed in slowing or preventing disease progression in patients who have newly diagnosed prostate cancer.

Detailed description: OBJECTIVES:

* Compare tumor proliferation in patients with newly diagnosed prostate cancer eating fat- and/or flaxseed-modified diets.
* Compare differences in histopathological markers associated with prostate cancer (rates of apoptosis, extent of high-grade prostatic intraepithelial neoplasia) among patients in these diet groups.
* Compare changes in serum prostate specific antigen among patients in these diet groups.
* Compare changes in hormone-related factors (total serum testosterone and free androgen index, insulin-like growth factor \[IGF\], and IGF-binding protein-3) among patients in these diet groups.
* Compare the effects of diet on nutritional biomarkers (levels of lignans in the urine and ejaculate, fatty acid profiles of erythrocytes and prostatic tissue) in these patients.
* Determine associations between dietary modification and changes in dietary biomarkers, hormonal intermediates, and study endpoints in these patients.

OUTLINE: This is a randomized study. Patients are stratified according to Gleason score (less than 7 vs at least 7) and race (black vs non-black). Patients are randomized to 1 of 4 diet groups.

* Arm I (Flaxseed-supplemented diet): Patients are instructed to incorporate ground flaxseed into their daily diets.
* Arm II (Low-fat diet): Patients are instructed on ways to achieve a diet with no greater than 20% of total energy from dietary fat.
* Arm III (Flaxseed-supplemented, low-fat diet): Patients are instructed as in arm I and arm II.
* Arm IV (Control diet): Patients are contacted weekly, but do not receive dietary counseling until after surgery.

All patients ingest the diets for at least 3 weeks and complete diet diaries until surgery. After surgery, all patients receive dietary counseling.

PROJECTED ACCRUAL: A total of 160 patients (40 per treatment arm) will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed prostate cancer
* At least 3 weeks until planned prostatectomy (24 days between day 1 visit and surgery)
* Current diet that provides more than 30% of calories from fat

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* Not specified

Life expectancy

* Not specified

Hematopoietic

* Not specified

Hepatic

* Not specified

Renal

* Not specified

Other

* Mentally competent
* Able to speak and write English
* Must have telephone access

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* Not specified

Endocrine therapy

* No concurrent hormonal therapy

Radiotherapy

* Not specified

Surgery

* At least 2 weeks since prior prostate biopsy

Other

* At least 7 days since prior antibiotics
* No prior therapy for prostate cancer
* No concurrent dietary supplements initiated within the past 3 months or anticipated to begin during study except standard multivitamin/mineral preparations (e.g., One-A-Day, Theragran, or Centrum) that do not supply \> 100% of the recommended daily allowance of any vitamin or mineral
* No other concurrent neoadjuvant therapies
* No other concurrent flaxseed consumption

Primary outcomes:
measure: Prostatic Carcinoma Proliferation Rate by MIB-1 assay at time of prostatectomy
Secondary outcomes:
measure: Prostatic Carcinoma Apoptotic Index by TUNEL assay at time of prostatectomy
measure: Prostate-specific antigen by Hybritech assay at baseline and follow-up
measure: Total testosterone, sex hormone binding globulin, insulin-like growth factor (IGF), and IGF-binding protein-3, total cholesterol, and low-density lipoprotein cholesterol by ELISA assays at baseline and follow-up
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: Duke Cancer Institute
name: Wendy Demark-Wahnefried, PhD
role: STUDY_CHAIR
References:
citation: Demark-Wahnefried W, Robertson CN, Walther PJ, Polascik TJ, Paulson DF, Vollmer RT. Pilot study to explore effects of low-fat, flaxseed-supplemented diet on proliferation of benign prostatic epithelium and prostate-specific antigen. Urology. 2004 May;63(5):900-4. doi: 10.1016/j.urology.2003.12.010.
citation: Lin X, Gingrich JR, Bao W, Li J, Haroon ZA, Demark-Wahnefried W. Effect of flaxseed supplementation on prostatic carcinoma in transgenic mice. Urology. 2002 Nov;60(5):919-24. doi: 10.1016/s0090-4295(02)01863-0.
citation: Demark-Wahnefried W, Polascik TJ, George SL, Switzer BR, Madden JF, Ruffin MT 4th, Snyder DC, Owzar K, Hars V, Albala DM, Walther PJ, Robertson CN, Moul JW, Dunn BK, Brenner D, Minasian L, Stella P, Vollmer RT. Flaxseed supplementation (not dietary fat restriction) reduces prostate cancer proliferation rates in men presurgery. Cancer Epidemiol Biomarkers Prev. 2008 Dec;17(12):3577-87. doi: 10.1158/1055-9965.EPI-08-0008.
citation: Demark-Wahnefried W, George SL, Switzer BR, Snyder DC, Madden JF, Polascik TJ, Ruffin MT 4th, Vollmer RT. Overcoming challenges in designing and implementing a phase II randomized controlled trial using a presurgical model to test a dietary intervention in prostate cancer. Clin Trials. 2008;5(3):262-72. doi: 10.1177/1740774508091676.
citation: Heymach JV, Shackleford TJ, Tran HT, Yoo SY, Do KA, Wergin M, Saintigny P, Vollmer RT, Polascik TJ, Snyder DC, Ruffin MT 4th, Yan S, Dewhirst M, Kunnumakkara AB, Aggarwal BB, Demark-Wahnefried W. Effect of low-fat diets on plasma levels of NF-kappaB-regulated inflammatory cytokines and angiogenic factors in men with prostate cancer. Cancer Prev Res (Phila). 2011 Oct;4(10):1590-8. doi: 10.1158/1940-6207.CAPR-10-0136. Epub 2011 Jul 15.
citation: Azrad M, Zhang K, Vollmer RT, Madden J, Polascik TJ, Snyder DC, Ruffin MT, Moul JW, Brenner D, Hardy RW, Demark-Wahnefried W. Prostatic alpha-linolenic acid (ALA) is positively associated with aggressive prostate cancer: a relationship which may depend on genetic variation in ALA metabolism. PLoS One. 2012;7(12):e53104. doi: 10.1371/journal.pone.0053104. Epub 2012 Dec 28.
citation: Azrad M, Vollmer RT, Madden J, Dewhirst M, Polascik TJ, Snyder DC, Ruffin MT, Moul JW, Brenner DE, Demark-Wahnefried W. Flaxseed-derived enterolactone is inversely associated with tumor cell proliferation in men with localized prostate cancer. J Med Food. 2013 Apr;16(4):357-60. doi: 10.1089/jmf.2012.0159.
citation: Azrad M, Vollmer RT, Madden J, Polascik TJ, Snyder DC, Ruffin MT 4th, Moul JW, Brenner D, He X, Demark-Wahnefried W. Disparate results between proliferation rates of surgically excised prostate tumors and an in vitro bioassay using sera from a positive randomized controlled trial. Biotech Histochem. 2015 Apr;90(3):184-9. doi: 10.3109/10520295.2014.976840. Epub 2014 Dec 1.