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Background: Cancer-related fatigue represents one major cause of reduced quality of life in cancer patients and can seriously affect the physical, emotional, and cognitive functioning impeding coping with the disease. Options for effective treatment of cancer-related fatigue are limited, consisting only of non-pharmacologic interventions like physical activity, psychosocial, and mind-body interventions. Recent evidence suggests that vitamin D3 supplementation might alleviate cancer-related fatigue. However, confirmation in a randomized controlled trial is needed.Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 456 colorectal cancer (CRC) patients aged 18 years and older are being recruited in three German rehabilitation clinics. Study inclusion requires hospitalization of at least 3 weeks at such a clinic, a diagnosis of non-metastatic CRC (stage I-III), surgical removal of the tumor within the past 9 months, and season-adapted vitamin D insufficiency or deficiency. Eligible patients are randomly assigned to a personalized regimen of vitamin D3 or placebo for 12 weeks. In the intervention group, a loading dose of 20,000 or 40,000 IU vitamin D3 will be administered daily during the first 11 days, followed by a maintenance dose of 2000 IU daily. Patients will complete questionnaires for secondary outcomes (fatigue subdomains, quality of life and subdomains, depression, functional well-being, and infection frequency). Blood and urine samples will be collected for analyses of safety parameters (hypervitaminosis D, hypercalcemia, hypercalciuria, and renal impairment) and efficacy biomarkers (25-hydroxyvitamin D, HbA1c, white blood cell count, leukocyte subtype counts, serum C-reactive protein, uric acid, creatinine, triglycerides, total, low- and high-density lipoprotein cholesterol).Discussion: This trial tests whether a personalized vitamin D3 dosing regimen reduces or prevents fatigue among non-metastatic CRC patients by treating the underlying vitamin D deficiency/insufficiency. If efficacy can be confirmed, personalized vitamin D3 supplementation could be used as a tertiary prevention measure in addition to non-pharmacological treatments of cancer-related fatigue in CRC patients. We expect to detect an effect of vitamin D3 supplementation on secondary outcomes like quality of life, depression, functional well-being, infections, inflammatory biomarkers, diabetes mellitus, and dyslipidemia.Trial Registration: European Clinical Trials Database: EudraCT-No: 2019-000502-30, January 21, 2019; German Clinical Trials Register (DRKS): DRKS00019907 , April 30, 2019. [ABSTRACT FROM AUTHOR]

ᅟ: Immunochemical fecal occult blood tests (iFOBTs) are increasingly used for colorectal cancer (CRC) screening. In our preceding observational study, sensitivity for detecting advanced colorectal neoplasms by iFOBT was 70.8% among users of low-dose acetylsalicylic acid compared with 35.9% among non-users (p = 0.001), whereas there were only very small differences in specificity. In receiver operating characteristics (ROC) analyses, the area under the curve (AUC) was much higher for acetylsalicylic acid users than for non-users, with particularly strong differences in men (0.87 versus 0.68, p = 0.003). These findings suggested that use of acetylsalicylic acid before conduct of iFOBT might be a promising approach to improve non-invasive screening for CRC.Methods/design: In this randomized, double-blind, placebo-controlled trial, the diagnostic performance of two iFOBTs for detecting advanced colorectal neoplasms after a single low-dose of acetylsalicylic acid (300 mg) compared to placebo is evaluated. Acetylsalicylic acid or placebo is administered at least 5 days before a planned, study-independent colonoscopic screening in 2400 participants aged 40 to 80 years. Stool samples are obtained before and on three different days after the single dose of acetylsalicylic acid or placebo. In addition, optional blood samples are taken for future biomarker analyses. The diagnostic performance of the iFOBTs will be compared to the results of the colonoscopy as a gold standard for the diagnosis of colorectal neoplasms. Additionally, gender-specific performance of the tests and gain in diagnostic performance by test application on multiple days will be evaluated.Discussion: If the findings from our preceding observational study will be confirmed in this large trial, the proposed low-risk, inexpensive intervention would considerably improve the diagnostic accuracy of iFOBTs and thus lead to enhanced early detection of colorectal neoplasms. Thus, the results of this trial may have a large public health impact.Trial Registration: This trial was registered before recruitment of the participants in www.clinicaltrialsregister.eu on the 30th of May 2012: EudraCT No.: 2011-005603-32 and in www.drks.de on 13th of March 2012: German Clinical Trials Register DRKS-ID: DRKS00003252 . [ABSTRACT FROM AUTHOR]