Title: Can Vitamin D Supplementation in Patients with Crohn's Disease Improve Symptoms as an Adjunct Therapy: ViDs Feasibility Study
Funder: Health Education England

Abstract: Background It is estimated that over 300,000 people in the UK are affected by Inflammatory Bowel Diseases (IBD). IBD refers to a group of chronic, debilitating diseases characterised by diarrhoea, malabsorption, abdominal pains, iron-deficiency anaemia, nutritional problems including Vitamin-D deficiency, and a poor health-related-quality-of-life. One of the principal diseases in this group is Crohn's Disease (CD), affecting approximately 115,000 people. CD may cause inflammation and ulceration anywhere within the gastro-intestinal tract. Vitamin-D deficiency is common in CD patients (approximately 68% of patients have deficient serum levels of 25hydroxy-vitamin D (25OHD) AimsInvestigate current clinical practice in detecting and treating Vitamin-D-deficiency in patients with CDUndertake a multi-centre randomised, feasibility trial to: Explore the acceptability, safety and feasibility of giving a daily oral vitamin supplement to CD patients with Vitamin-D-deficiency Explore the feasibility of proposed clinical measures including multiple Vitamin-D metabolites, hepcidin and iron serum levels and health-related-quality-of-life measures in patients with CDEstimate the proportion of eligible patients successfully recruited compared to the proportion of participants who complete the study.Plan of investigation Part 1 Current Practice SurveyA questionnaire will be developed and sent electronically to Gastroenterology healthcare professionals to explore: if Vitamin-D screening is routine, what factors would prompt healthcare professionals to check Vitamin-D levels and what treatment would be recommended for Vitamin-D-deficiency.Part 2 Screening and Recruitment for a Feasibility StudyEstimate prevalence of Vitamin-D-deficiency in patients with CD seen at University Hospital Birmingham Foundation Trust and Heart of England Foundation Trust during February, March and April when Vitamin-D-deficiency is likely to be most prevalent. Explore lifestyle influences on Vitamin-D levels including diet and sun exposure. Recruit eligible patients to participate in the feasibility study. Repeat Vitamin-D screening in June, July and August to test the feasibility of recruitment throughout the year. Part 3 Feasibility StudyRandomise participants with 25(OH)D Patient Benefit A full RCT will add to the current body of evidence and inform national guidance regarding the management of patients with CD. However, as per Medical Research Council guidelines smaller feasibility studies should be conducted first to test methodology and establish parameters for a full RCT. This will help ensure success and appropriate use of resources in a substantive trial. The primary outcome of the substantive RCT will provide evidence for routine monitoring of Vitamin-D levels as part of CD management and for this to be incorporated in to NICE CD recommendations . There is currently no agreed dose for Vitamin-D supplementation in CD. Therefore, a further intended outcome of a substantive RCT would be to compare and test two different doses of Vitamin-D supplementation in patients with CD.

Lay abstract: Background Crohn's Colitis UK has estimated that there are over 300,000 people in the UK living with Inflammatory Bowel Diseases (IBD). IBD refers to a group of chronic diseases that cause inflammation and ulceration in the gut. One of the main diseases is Crohn's Disease which can affect any part of the gut. People with Crohn's Disease suffer from symptoms that include:DiarrhoeaAbdominal painIron-deficiency anaemiaNutritional problems including Vitamin-D-deficiencyA poor quality-of-life as a result of their Crohn's DiseaseResearch in the UK has found that Vitamin-D-deficiency is common in over two-thirds of people with Crohn's Disease. This is because people with Crohn's Disease have difficulty absorbing nutrients. They have also found that about half of people with Crohn's Disease have anaemia. Iron is used in the body to make red blood cells. These cells help store and carry oxygen in the blood. Anaemia is a condition where there is a lack of iron in the body which causes a reduction in the number of red blood cells. Other research has discovered that taking a Vitamin-D supplement sometimes improves the symptoms for people with Crohn's Disease. This may be because Vitamin-D:Helps reduce inflammation.Prevents the liver from making too much of the hormone hepcidin, which allows the gut to absorb more iron from food and might help to lessen anaemia.There are national guidelines regarding the medical management of Crohn's Disease. However, these guidelines do not give advice on how often to check for Vitamin-D-deficiency. Advice is also needed on the most effective method to treat Vitamin-D-deficiency in people with Crohn's Disease. Aims: Investigate current clinical practice in detecting and treating Vitamin-D-deficiency.Investigate the feasibility of carrying out a large randomised-controlled trial of Vitamin-D screening and supplementation in people who have Crohn's Disease.Method: Part 1 Current Practice Survey: we will carry out a survey to ask doctors and nurses whether they routinely check for Vitamin-D-deficiency and how they would treat this in people with Crohn's Disease. Part 2 Screening: At their routine Crohn's Disease clinic appointments, we will invite people to take a finger-prick blood test to check their Vitamin-D levels to establish if they have Vitamin-D-deficiency. This will be for patients who visit the University Hospital Birmingham Foundation Trust or Heart of England Foundation Trust for their appointment February-April, when people are most likely to have Vitamin-D-deficiency. We will ask questions about their diet and exposure to sunlight during the winter months, such as recent holidays to a hot country. This is important because Vitamin-D can be made by the body from exposure to sunlight. There is also Vitamin-D in some foods, such as oily fish. Part 3 Feasibility Study: We will invite people who have Vitamin-D-deficiency to join a feasibility study where they will be asked to take a daily Vitamin-D supplement by mouth for 6 months. Half of the participants will be treated with a low dose and the other half treated with a higher dose. We will randomly allocate participants to either group. We will carry out blood tests at the start, after 3 months and after 6 months of starting the supplement. We will also ask participants to complete quality of life questionnaires. During the feasibility study we will check if:Participants find it acceptable to take the daily supplementParticipants find it acceptable to have blood tests and complete the questionnairesIt would be feasible to carry out the same study in a large number of peopleParticipants We will include people who are:Aged 18 years or olderAlready having treatment for Crohn's Disease or those who have Crohn's Disease but not currently needing treatmentAble to provide informed written consent to take partPatient and Public Involvement A group of patients, who have IBD, has been involved in the design of this study including the development of the research question and the method. Patient representatives will form part of the Trial Management Group and Trial Steering Committee and will help with dissemination of results. Dissemination Findings will be shared with patient groups such as Crohn's Colitis UK. Results will also be published in medical and research journals to share with other healthcare professionals and researchers. The results will be used to help design a much larger randomised-controlled trial. The larger trial will provide important evidence on whether Vitamin-D supplements do improve symptoms for sufferers of Crohn's Disease who have Vitamin-D-deficiency. These results may then be used to update national guidelines regarding management of this disease.

Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION;6.1 PHARMACEUTICALS
Health categories: ORAL AND GASTROINTESTINAL