Comprehensive Lifestyle Improvement Program for Prostate Cancer (CLIPP) is associated with improvement in weight and components of metabolic syndrome in men exposed to androgen deprivation therapy for prostate cancer.

BACKGROUND: Androgen deprivation therapy (ADT) for prostate cancer is associated with adverse effects, such as obesity and metabolic syndrome, which increase cardiovascular risk, the most common cause of non-cancer mortality in men diagnosed with prostate cancer. The Comprehensive Lifestyle Improvement Program for Prostate Cancer (CLIPP) was created to determine the feasibility of conducing a comprehensive lifestyle modification intervention in men on ADT for prostate cancer and determine its early efficacy in reducing obesity and metabolic syndrome. METHODS: A single-arm, open-label clinical trial was conducted by recruiting 31 men diagnosed with prostate cancer and exposed to ADT within the last 5 years. A multicomponent lifestyle modification program was delivered weekly for 16 weeks by a trained health coach. This was followed by 8 weeks of passive follow-up resulting in a total trial duration of 24 weeks. Feasibility was determined by calculating study recruitment, retention, and adherence rates. Weight and components of metabolic syndrome (waist circumference, triglycerides (TG), high-density lipoprotein (HDL), serum glucose, and blood pressure (BP)) were measured at baseline, 12, and 24 weeks. RESULTS: Recruitment, retention, and adherence rates were 47.1%, 90.3%, and 100%, respectively. Statistically significant improvements were noted between baseline and end of study measurements for weight (206.3 vs. 191.3 lbs, p < 0.001), waist (41.3 vs. 38.8 inches, p < 0.001), systolic BP (144.1 vs. 133.4 mm of Hg, p = 0.014), diastolic BP (83.3 vs. 76.2 mm of Hg, p = 0.0056), TG (146.0 vs. 113.8 mg/dl, p = 0.022), HDL (51.1 vs. 55.0 mg/dl, p = 0.012), and serum glucose (114.0 vs. 103.2 mg/dl, p = 0.013). CONCLUSION: CLIPP demonstrates feasibility and early efficacy of a multicomponent lifestyle modification intervention toward addressing obesity as well as components of metabolic syndrome in men on ADT for prostate cancer. This study provides strong preliminary data to develop future clinical trials in this population.

Protocol for a feasibility and early efficacy study of the Comprehensive Lifestyle Improvement Program for Prostate Cancer-2 (CLIPP2).

BACKGROUND: Although androgen deprivation therapy (ADT) for prostate cancer demonstrates improved overall and disease-free survival, it is associated with adverse effects such as obesity and metabolic syndrome that increase risk of cardiometabolic disease and diabetes type 2. ADT also leads to fatigue, depression and erectile dysfunction, which reduce quality of life (QoL). Lifestyle modification has shown promise in reducing obesity, metabolic syndrome and diabetes type 2 in other disease types. However, there is a paucity of data regarding the utility of lifestyle modification in men receiving ADT for prostate cancer. METHODS: The primary aim of the Comprehensive Lifestyle Improvement Program for Prostate Cancer-2 (CLIPP2) is to test the feasibility of conducting a 24-week lifestyle modification intervention in men on ADT for prostate cancer. Additionally, it will also determine the effect of this intervention on weight loss, cardiometabolic markers (secondary aim and markers of interest: serum glucose, insulin resistance, hemoglobin A1C and lipid panel), and QoL (tertiary aim). The intervention will be delivered weekly via telephone for the first 10 weeks and bi-weekly for the remaining 14 weeks. Questionnaires and serum samples will be collected at baseline, week 12, and week 24. Anthropometric measurements will be collected at baseline, week 6, week 12, week 18 and week 24. RESULTS: We hypothesize that the CLIPP2 intervention will produce a 7% weight loss that will result in improved markers associated with cardiometabolic disease and type 2 diabetes in the study population. CONCLUSION: Results will provide insight into the role of lifestyle modification in addressing ADT adverse effects as well as provide preliminary data to inform the development of future lifestyle interventions in this area. TRIAL REGISTRATION: NCT04228055 Clinicaltrials. gov.

EFFECT OF SELENIUM SUPPLEMENTATION ON PROTEOMIC SERUM BIOMARKERS IN ELDERLY MEN.

OBJECTIVES: To determine the effect of selenium supplementation on the human proteomic profile. DESIGN: Serum samples were collected in this pilot study from a randomized placebo controlled Phase 2 clinical trial (Watchful Waiting (WW)). SETTING: Subjects were followed every three months for up to five years at the University of Arizona Prostate Cancer Prevention Program. PARTICIPANTS: One hundred and forty men (age < 85 years) had biopsy-proven prostate cancer, a Gleason sum score less than eight, no metastatic cancer, and no prior treatment for prostate cancer. INTERVENTION: As part of the WW trial, men were randomized to placebo, selenium 200 µg/day or selenium 800 µg/day. For the purpose of the current study, 40 subjects enrolled in the WW study (20 from the placebo group and 20 from Se 800 µg/day group) were selected. MEASUREMENTS: Baseline serum samples were collected at each follow-up visit and stored at -80 degrees Celsius. A multiplexed proteomic panel investigated changes in 120 proteins markers simultaneously. RESULTS: Thirteen proteins (Apolipoprotein J, IL-10, IL-1 alpha, MMP-3, IL-12p70, IL-2 receptor alpha, cathepsin B, eotaxin, EGFR, FGF-basic, myeloperoxidase, RANTES, TGF-beta) were determined to be either statistically (p-value < 0.05) or marginally significantly (0.05 < p-value <0.1) changed in the selenium supplemented group as compared to placebo. CONCLUSION: Although independent validation of these results is needed, this study is the first of its kind to utilize high throughput fluorescence based protein multiplex panel in analyzing changes in the proteomic profile due to selenium supplementation. Results from this study provide insight into the ability of selenium to modulate numerous protein markers and thus impact various biological processes in humans.

Differences in characteristics of men with localised prostate cancer who demonstrate low, intermediate or high prostate-specific antigen velocity.

BACKGROUND: Current diagnostic tools are inadequate for reliable prediction of prostate cancer (PCa) aggressiveness in patients with localised disease. This results in many patients being exposed to potentially unnecessary invasive treatment and its associated morbidities. In order to develop appropriate treatment strategies, it is essential to understand the differences between patients who will develop aggressive disease and those who will not. METHODS: A longitudinal study was conducted in men with localised PCa on active surveillance for their disease in which 140 subjects were followed every 3 months for up to 5 years. Change in prostate-specific antigen (PSA) over time (PSA velocity) was used as a marker for PCa progression. Subjects were categorised as slow, intermediate and fast progressors based on tertiles of PSA velocity. Differences in baseline markers were investigated using logistic regressions. Two approaches were used, slow progressors were compared with fast progressors (model 1) and slow progressors were compared with combination of intermediate and fast progressors (model 2). RESULTS: Aspirin was negatively associated with high PSA velocity in model 1 (odds ratio (95% confidence interval): 0.24 (0.06, 0.94), P-value = 0.04) and model 2 (odds ratio = 0.22 (0.08, 0.59), P-value = 0.003), whereas smoking was positively associated with high PSA velocity in model 1 (1.03 (0.92, 1.13), P-value = 0.01). CONCLUSIONS: These findings highlight the role of aspirin and smoking in PCa progression. They have potential towards risk stratification as well as PCa prevention and hence need to be investigated further.