Multiple studies, including our own, have consistently shown that fatigue is common among colorectal cancer (CRC, also known as bowel cancer) patients. Fatigue is experienced, not only shortly after diagnosis and initial treatment, but also in the long run, and is associated with low quality of life (QoL) and disability.
Blood vitamin D levels are very low in many CRC patients. Recent observational studies have found a link between low blood vitamin D levels and fatigue, exhaustion and frailty, both in cancer patients and in the general elderly population.
This suggests that giving vitamin D supplements to vitamin D-deficient cancer patients might be a promising approach to alleviate fatigue. However, confirmation in a controlled study is needed.
The proposed trial will be the first to address the effects of vitamin D supplementation on fatigue as a primary outcome in CRC patients.
Aims and objective
The main aim of this trial is to test whether vitamin D supplementation improves fatigue, and subsequently QoL, in CRC patients with vitamin D deficiency and mild to severe fatigue.
How it will be done
Five rehabilitation clinics in Germany agreed to recruit 410 CRC patients, the number needed to detect if there is a clinically relevant difference in fatigue between the vitamin D and the placebo group. Of this, 205 will receive vitamin D and 205 will receive nothing – neither group will know if they are receiving vitamin D or not.
We will include CRC patients in the trial who were sent into the rehabilitation clinic within six months after first diagnosis of CRC, have mild or severe fatigue, and have vitamin D deficiency.
Vitamin D will be given as an initial personalised vitamin D dose and then a maintenance dose of 1,500 IU vitamin D per day for 12 weeks. The initial dose will be high enough to elevate blood vitamin D levels to the optimal level of 75 nanomoles per litre (nmol/L) and will be calculated based on an equation that takes the person’s blood vitamin D level at the beginning of the study, and body weight, into account.
We expect an average initial dose of 180,000 IU vitamin D and for safety reasons we will not give anyone more than 360,000 IU vitamin D. The effect of the vitamin D treatment will be addressed with questionnaires to assess fatigue and QoL. The questionnaires will be sent to the study participants after vitamin D capsules and tablets are used up at the end of the trial (in trial week 13–16).
The safety of the study participants will be ensured by checking blood levels of vitamin D, parathormone, calcium, phosphate and creatinine, and the urine levels of calcium at the beginning, week two–three and at the end of the trial (week 13–16).
Options for effective prevention or treatment of fatigue have remained very limited and include non-drug interventions, such as physical activity, psychosocial interventions, and mind-body interventions.
Preventing or alleviating fatigue by a drug, such as vitamin D3, could add to these treatments and substantially increase the QoL of CRC survivors, empower them in coping with their disease, and reduce disease and disability-related direct and indirect costs.
The results of the trial can be translated into routine practice because the trial population is representative of CRC patients with vitamin D deficiency and mild to severe fatigue. Therefore, if the trial results could be used for a policy change that implements a cost-effective, routine vitamin D deficiency screening programme and treatment in rehabilitation clinics for CRC patients, this could have a large impact on the fatigue, QoL and potentially also survival of this patient group.