Effects of EPA on Prostate Cancer Cells Proliferation and Quality of Life

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Prostate Cancer

Intervention / Treatment
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* Dietary Supplement: EPA
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostatectomy, Omega-3 fatty acids, Quality of life, inflammation, cellular proliferation