Effects of EPA on Prostate Cancer Cells Proliferation and Quality of Life (RCT-EPA)

Étude randomisée, contrôlée, de Phase II, Effets d'un Supplement d'oméga-3 (EPA) Sur l'Inflammation, la prolifération Cellulaire et la qualité de Vie Chez Des Patients Avec Cancer de la Prostate traités Par Prostatectomie Radicale

Prostate cancer, the most frequently diagnosed cancer among occidental men, is associated with a major individual and societal burden. Although still controversial, the literature suggests that a high consumption of omega-3 fatty acids (ω3) has protective effects against prostate cancer. One of the proposed mechanisms of action of ω3 lies in their anti-inflammatory properties. In addition, there are some observational evidences suggesting an association of ω3 intake with a lower rate of depression in cancer patients. However, no clinical study has tested the efficacy of ω3 supplementation on psychological and quality of life outcomes in that population. Several evidences point to a possible involvement of inflammation in psychological issues. Reducing the systemic inflammatory state may have beneficial impact on the quality of life of these patients. Preliminary work from this team of investigators, in a cohort of patients managed with active surveillance for their low-grade prostate cancer, show a strong inverse association between the risk of prostate cancer progression (to high-grade) and the level of prostatic eicosapentanoic acid (EPA- a type of ω3).

HYPOTHESIS: EPA-rich monoglycerides fish oil (MAG-EPA) has global positive effects on prostate cancer cell proliferation, inflammation and on the patient's psychosocial functioning and quality of life.

The investigators propose a double blind, randomized controlled clinical trial. 130 consecutive patients suffering from high-risk prostate cancer who choose to be treated by radical prostatectomy will be eligible to this study. The presence of high-grade cancer will be mandatory.

The intervention, a daily supplementation with 3g supplement of fish oil monoglycerides rich in EPA, vs. placebo capsules containing high oleic sunflower oil, will start six weeks before the prostatectomy and will continue for one year after surgery. The potential confounding variables will be measured before the start of the intervention: age, anthropometric parameters, stage and clinical and pathological tumor grade (Gleason score), pre-operative level of prostate specific antigen and diet.

This project proposes a simple intervention by dietary supplementation that could eventually help to reduce the incidence and/or progression of prostate cancer, and the consequences of its treatment, and thus could contribute to diminish the heavy individual and societal burden of prostate cancer. The clinical data generated by this trial will serve as solid basis for a large-scale phase III clinical trial.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Dietary supplement: EPA; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1R 3S1
    • Centre de Recherche Clinique et Evaluative en Oncologie - Hotel Dieu de Quebec

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Prostate cancer (Gleason score >= 7)
• Patient has chosen to undergo radical prostatectomy
• Patient agrees to stop taking any omega-3 supplements at least 3 months before the start of the study
• Patient has provided informed consent

Exclusion Criteria:

• Allergy to fish and sunflower
• Suffering from a bipolar disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Purified EPA group; 3g per day of purified EPA, capsules, to be taken once a day, for 14 months.	Dietary supplement: EPA; 3g/day of purified EPA , capsules, taken once daily, for 14 months
Experimental: Placebo group; 3 g per day of high-oleic sunflower oil capsules, to be taken once a day, for 14 months.	Dietary supplement: Placebo; 3g/day of placebo (high oleic sunflower oil) , capsules, taken once daily, for 14 months; Other Names: High oleic sunflower oil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Prostate Cancer Proliferative Index	At 6 weeks post study entry, the prostate of the patient will be removed by prostatectomy. The tissue will be preserved in paraffin blocks. The tumour will be identified and the level of Ki-67 in the tumour will be quantified.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Inflammatory mediators levels- Systemic	The changes in levels of systemic inflammatory mediators, relative to their baseline levels, at the time of radical prostatectomy and at one year post-radical prostatectomy, will be measured. The levels of mediators will be expressed in pg/mL and quantified using validated techniques.	6 weeks, 1 year
Modulation of Inflammatory mediators levels - Prostatic	The differences in the levels of expression of inflammatory mediators between both treatment groups will be measured in the peripheral zone of the prostate before surgical prostate dissection/ischemia. The levels of mediators will be expressed in pg/mL and quantified using validated techniques. Further validation could be performed using immunohistochemistry techniques.	6 weeks, 1 year
Modulation of the Quality of life of patients	Validated questionnaires will be used to measure the modulation of the treatment on Quality of Life of the patients, which will include questions on mood, anxiety levels, sleep and cognition.	6 weeks, 3, 6, 9 and 12 months post radical prostatectomy
Modulation of the psychosocial functioning of patients	Validated questionnaires will be used to measure the modulation of the treatment on psychosocial functioning of the patients, which will include questions on mood, anxiety levels, sleep and cognition.	6 weeks, 3, 6, 9 and 12 months post radical prostatectomy
Impact of inflammation on Quality of life	The impact of changes in inflammatory mediators levels induced by EPA supplementation on quality of life scores will be measured. To do so, we will use appropriate and powerful statistical tests.	6 weeks, 3, 6, 9 and 12 months post radical prostatectomy
Impact of inflammation on psychosocial functioning	The impact of changes in inflammatory mediators levels induced by EPA supplementation and changes in psychosocial functioning scores will be measured. To do so, we will use appropriate and powerful statistical tests.	6 weeks, 3, 6, 9 and 12 months post radical prostatectomy

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatty acid profiles in red blood cell membranes, change relative to baseline	The difference of fatty acid levels between both groups, relative to baseline, will be quantified using gas chromatography coupled with mass spectrometry and expressed as relative percentages of total fatty acids.	6 weeks, 3, 6, 9, 12 months post radical prostatectomy
Fatty acid profiles in prostate tissue	The difference of fatty acid levels between both groups at prostatectomy will be quantified using gas chromatography coupled with mass spectrometry and expressed as relative percentages of total fatty acids, and in absolute level (mg per gram of tissue).	6 weeks
Impact of EPA supplementation on radical prostatectomy complications	The difference in perioperative bleeding, laboratory tests (hemoglobin, hematocrit and platelets) and surgical complications between both group will be examined at surgery.	6 weeks
Impact of EPA supplementation on cancer aggressiveness	Pathological reclassification of cancer grade (ISUP grading system) and stage between the prostate diagnostic biopsy and the prostatectomy specimen will be compared between both groups.	6 weeks
Change on PSA level (ng/mL), relative to baseline	PSA change relative to baseline will be measured for both groups.	6 weeks, 3, 6, 9 and 12 months post radical prostatectomy
Impact of EPA supplementation on biochemical recurrence	The biochemical recurrence, defined as a PSA level ≥ 0.2 ng/mL after reaching a non-detectable level at three months post-surgery, will be evaluated for both groups.	5 years post radical prostatectomy

Collaborators and Investigators

• Sponsor: CHU de Quebec-Universite Laval
• Investigators: Principal Investigator: Vincent Fradet, MD, PhD, Laval University and Hotel Dieu-de-Quebec

Publications and helpful links

General Publications

• Guertin MH, Robitaille K, Pelletier JF, Duchesne T, Julien P, Savard J, Bairati I, Fradet V. Effects of concentrated long-chain omega-3 polyunsaturated fatty acid supplementation before radical prostatectomy on prostate cancer proliferation, inflammation, and quality of life: study protocol for a phase IIb, randomized, double-blind, placebo-controlled trial. BMC Cancer. 2018 Jan 10;18(1):64. doi: 10.1186/s12885-017-3979-9.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): December 1, 2020
• Study Completion (Estimated): December 1, 2023

Study Registration Dates

• First Submitted: December 17, 2014
• First Submitted That Met QC Criteria: January 5, 2015
• First Posted (Estimated): January 7, 2015

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: June 6, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Quality of life; inflammation; Omega-3 fatty acids; Prostatectomy; cellular proliferation
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 2012-1012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED