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Placebo-controlled, randomized clinical trial of high-dose cholecalciferol in renal dialysis patients: effect on muscle strength and quality of life.
Singer, R, Chacko, B, Talaulikar, G, Karpe, K, Walters, G
Clinical kidney journal. 2019;(2):281-287
Abstract
BACKGROUND The importance of vitamin D sufficiency in deficient dialysis patients is uncertain. This study aimed to determine if high-dose cholecalciferol for 1-year affected symptoms, muscle strength, blood pressure (BP), cardiac ischaemia, parathyroid hormone, calcium or phosphate. METHODS This was a randomized, double-blind, placebo-controlled trial with 1-year follow-up that enrolled dialysis patients with 25-hydroxy-vitamin D [25(OH)D] concentration <50 nmol/L. Consenting patients were randomized to 50 000 U/week oral cholecalciferol or matching placebo. Dosage was adjusted at 3- and 6-month study visits, targeting a 25(OH)D concentration >80 nmol/L. The primary objectives were to assess the effect of supplementation on renal-specific symptoms and on hand-grip strength. Symptoms were assessed using the Kidney Disease Quality of Life Short Form and muscle strength with a hand grip-strength dynamometer. Hypothesis testing was by two-group t-test and Wilcoxon rank-sum on an intention-to-treat basis. RESULTS In all, 68 participants were randomized and received study medication. Median 12-month plasma 25(OH)D concentration was 119 nmol/L and 37 nmol/L in the cholecalciferol and placebo groups, respectively. There was no statistical difference in primary outcomes at 12 months. Mean symptom scores at 12 months were two lower in the cholecalciferol group (95% confidence interval -10 to 6) and geometric mean grip-strength was 27 kg in both groups. Symptoms, strength, BP, plasma mineral bone parameters and adverse events were not different between the groups at follow-up. CONCLUSIONS High-dose cholecalciferol in a deficient dialysis population had no effect on muscle strength or symptoms but appears safe.
2.
Feasibility outcomes of a presurgical randomized controlled trial exploring the impact of caloric restriction and increased physical activity versus a wait-list control on tumor characteristics and circulating biomarkers in men electing prostatectomy for prostate cancer.
Demark-Wahnefried, W, Nix, JW, Hunter, GR, Rais-Bahrami, S, Desmond, RA, Chacko, B, Morrow, CD, Azrad, M, Frugé, AD, Tsuruta, Y, et al
BMC cancer. 2016;16:61
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There is a strong body of evidence associating obesity and increased risk for more aggressive and progressive cancer. This paper aims to assess the feasibility of a presurgical diet and exercise weight loss intervention in men with newly-diagnosed prostate cancer who elected for prostatectomy. It also aims to explore the intervention’s effects on tumour proliferation rates and other biomarkers. The 3-weeks randomised controlled study included 40 overweight or obese men newly-diagnosed with prostate cancer. Participants in experimental arm were assigned to a healthy energy-restricted diet versus wait-list control arm. All feasibility endpoints were achieved with accrual completed within 2 years, retention of 85%, adherence of 95% and no adverse events. Biologic outcomes were not included in this paper, as biological testing was still ongoing. Authors concluded that this study’s methods and data on feasibility could provide useful framework for the design of future trials. They also highlighted the importance of presurgical trials as a feasible and safe means to assess the impacts of diet and exercise on tumour tissue.
Abstract
BACKGROUND Obesity is associated with tumor aggressiveness and disease-specific mortality for more than 15 defined malignancies, including prostate cancer. Preclinical studies suggest that weight loss from caloric restriction and increased physical activity may suppress hormonal, energy-sensing, and inflammatory factors that drive neoplastic progression; however, exact mechanisms are yet to be determined, and experiments in humans are limited. METHODS We conducted a randomized controlled trial among 40 overweight or obese, newly-diagnosed prostate cancer patients who elected prostatectomy to explore feasibility of a presurgical weight loss intervention that promoted a weight loss of roughly one kg. week(-1) via caloric restriction and physical activity, as well as to assess effects on tumor biology and circulating biomarkers. Measures of feasibility (accrual, retention, adherence, and safety) were primary endpoints. Exploratory aims were directed at the intervention's effect on tumor proliferation (Ki-67) and other tumor markers (activated caspase-3, insulin and androgen receptors, VEGF, TNFβ, NFκB, and 4E-BP1), circulating biomarkers (PSA, insulin, glucose, VEGF, TNFβ, leptin, SHBG, and testosterone), lymphocytic gene expression of corresponding factors and cellular bioenergetics in neutrophils, and effects on the gut microbiome. Consenting patients were randomized in a 1:1 ratio to either: 1) weight loss via a healthful, guidelines-based diet and exercise regimen; or 2) a wait-list control. While biological testing is currently ongoing, this paper details our methods and feasibility outcomes. RESULTS The accrual target was met after screening 101 cases (enrollment rate: 39.6%). Other outcomes included a retention rate of 85%, excellent adherence (95%), and no serious reported adverse events. No significant differences by age, race, or weight status were noted between enrollees vs. non-enrollees. The most common reasons for non-participation were "too busy" (30%), medical exclusions (21%), and "distance" (16%). CONCLUSIONS Presurgical trials offer a means to study the impact of diet and exercise interventions directly on tumor tissue, and other host factors that are feasible and safe, though modifications are needed to conduct trials within an abbreviated period of time and via distance medicine-based approaches. Pre-surgical trials are critical to elucidate the impact of lifestyle interventions on specific mechanisms that mediate carcinogenesis and which can be used subsequently as therapeutic targets. TRIAL REGISTRATION NCT01886677.