Vitamin D supplementation in patients with Crohn’s Disease and vitamin D deficiency: D-CODE feasibility study. An open label feasibility study for a randomised controlled trial

Fletcher, Jane ORCID: 0000-0001-5033-8278 (2023). Vitamin D supplementation in patients with Crohn’s Disease and vitamin D deficiency: D-CODE feasibility study. An open label feasibility study for a randomised controlled trial. University of Birmingham. Ph.D.

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Abstract

Introduction:
Crohn’s Disease (CD) is one form of Inflammatory Bowel Disease (IBD) characterised by severe diarrhoea, abdominal pain, and nutritional problems. Vitamin D deficiency (25(OH)D<50nmol/L) is prevalent in CD, posing the risk of bone disease such as osteoporosis. However, studies suggest that vitamin D deficiency may also impact the symptoms of CD, and lead to poor health-related quality of life. Thus, detecting, treating, and preventing vitamin D deficiency in CD may improve patient outcomes. Nevertheless, current UK national guidance regarding the management of CD does not refer to vitamin D in this high-risk group.

Methods:
The method of investigation comprised three different studies: A, B and C.

A – A web-based quantitative/qualitative survey investigating current clinical practice in vitamin D screening and treatment in CD, was distributed to members of the British Society of Gastroenterology IBD section. The survey was open for one month. Survey data was collected using the REDCap online tool.

B – An observational, vitamin D screening study was carried out in the gastroenterology and infusion outpatient departments at the Queen Elizabeth Hospital Birmingham (QEHB). Vitamin D levels were measured by dried blood spot sample. Data regarding modifiable risk factors for vitamin D deficiency were collected including intake of vitamin D-containing foods, smoking and, sun exposure habits.

C – The D-CODE feasibility study for an open label randomised controlled trial (RCT) determining the impact of vitamin D supplementation on health-related quality of life in CD was carried out at QEHB. Only participants identified from study B with identified vitamin D deficiency were recruited. Participants were randomised on a 1:1 ratio to vitamin D supplementation Arm A (400IU cholecalciferol daily for 24 weeks) or Arm B (3,200IU cholecalciferol daily for 12 weeks, followed by 800IU daily for 12 weeks). Patient-reported outcome measures included the IBDQ-32 and EQ-5D-5L.

Results:
A – In total 62 respondents completed the survey. Vitamin D screening was most likely to be carried out annually and in those with small bowel CD or surgery related to their CD. Treatments for vitamin D deficiency included increasing sunlight exposure, dietary changes, and supplementation. However, respondents reported a need for better evidence and national guidance in managing this group.

B – In total 150 patients participated, 53.3% female, mean age 42.7 (SD16.7), ethnicity of participants was predominately white British (77.3%). Prevalence of vitamin D deficiency (25(OH)D <50nmolL) was 53.3%, with CD patients unlikely to improve vitamin D status by alterations in diet or sun exposure.

C – In total 24 patients were consented and 22 randomised. Males and females were evenly matched in both arms, with mean ages 37 (SD15.1) and 38.2 (SD17.5) respectively. Vitamin D levels increased in both arms but was more rapid in Arm B with normal levels achieved by week 12. There were no serious adverse events and doses of vitamin D supplements were safe in the context of this study. The study is feasible with modifications as a future RCT.

Conclusion:
This thesis follows a logical pathway in establishing current practice, adding to the body of evidence on the prevalence of vitamin D deficiency, and confirming the feasibility of a future RCT to provide high-grade evidence for clinical management in CD.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):