Condition category
Digestive System
Date applied
28/01/2019
Date assigned
01/03/2019
Last edited
22/03/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
About half to three-quarters of people with Crohn’s Disease may develop vitamin D deficiency (very low levels of vitamin D in the body). Vitamin D is very important to help maintain healthy bones. Recent research has found that for people with Crohn’s Disease, having normal levels of vitamin D might also help to improve the symptoms of their disease. Despite this vitamin D levels are not routinely checked for people with Crohn's Disease. There are many different doses and types of vitamin D available on prescription and over the counter but there is no standard treatment for vitamin D deficiency in Crohn's Disease. The aim of this study is to compare two different doses of vitamin D capsules to treat vitamin D deficiency in adults with Crohn's Disease. The aims of the study are to:
Understand what proportion of people with Crohn's Disease have vitamin D deficiency at the end of the winter and during the summer months.
Understand any specific factors that might contribute to vitamin D deficiency in people with Crohn's Disease.
Find out if it is possible to carry out the study with a large number of people to see which dose of vitamin D is best at treating vitamin D deficiency in people with Crohn's Disease

Who can participate?
Vitamin D Screening studies: Adult patients with Crohn’s Disease who have their usual care at one of the participating hospitals
Vitamin D Supplementation trial: Adult patients with Crohn’s Disease who have been found to have vitamin D deficiency in the winter vitamin D screening study

What does the study involve?
Vitamin D Screening studies: Participants have a finger-prick blood test to measure their vitamin D levels. They also answer questions about their diet and lifestyle that might influence their vitamin D levels.
Vitamin D Supplementation trial: All participants receive a vitamin called D3 (cholecalciferol). The capsule is taken once a day by mouth. Participants in one group get a different treatment than participants in another group. There are two treatment groups: one group receive vitamin D3 400 iu, one capsule daily for24 weeks. The other group receive vitamin D3 3,200 iu one capsule daily for 12 weeks and then vitamin D3 800 iu one capsule daily for 12 weeks. A number of blood samples and a stool sample are taken to monitor the safety and effectiveness of the treatment. Blood tests and stool samples are taken at the start, after 12 weeks and then at the end of 24 weeks. Participants complete questionnaires at the start of the study and at the end of 24 weeks and keep a diary of when they have taken their vitamin D capsules each day. It is expected that each study appointment may take up to 40 minutes to complete. Appointments are carried out at the hospital participants usually attend for their Crohn's Disease follow-up.

What are the possible benefits and risks of participating?
Vitamin D Screening studies: It is hoped that the results from the study will help doctors and patients in the future when making decisions about treatment. There should not be any risks involved in taking part in the Vitamin D Screening Study. Some people may find the finger-prick blood test uncomfortable. Four large spots of blood are needed for the test. If it is difficult to get enough drops of blood from the first finger prick it may need to be repeated. The researchers will try to take the samples from the least sensitive part of the fingertip.
Vitamin D Supplementation trial: It is hoped that the results from the study will help inform a large study that will help doctors and patients in the future when making decisions about treatment for people with Crohn's Disease. Both treatments have been shown to treat or prevent vitamin D deficiency, but it cannot be guaranteed that either treatment will make any difference to the symptoms of Crohn's Disease. The main risk of taking any vitamin D supplement is developing too much calcium in the blood (hypercalcaemia). Hypercalcaemia may also lead to calcium in the urine (hypercalciuria). This risk is classed as 'uncommon' but if this happened the main symptoms would be: nausea, vomiting, passing large amounts of urine, loss of appetite, weakness, apathy, thirst, constipation. For this reason calcium blood levels will be checked at the beginning of the study to ensure they are normal, and at the 12 week and 24 week appointments along with other safety blood measures to ensure they remain within safe limits. Rarely some people report developing a rash when they take a vitamin D capsules. Participants will need to have three sets of blood tests over the whole study duration. Some people may find these uncomfortable and there may be some bruising afterwards but samples will be taken by an appropriately trained person.

Where is the study run from?
1. Queen Elizabeth Hospital Birmingham (UK)
2. Birmingham Heartlands Hospital (UK)
3. Good Hope Hospital (UK)

When is the study starting and how long is it expected to run for?
Vitamin D Screening will be starting in March 2019 and will continue for about 2 months. The participants in the vitamin D supplementation study will be in the study for a total of 36 weeks.

Who is funding the study?
National Institute for Health Research (NIHR) (UK)

Who is the main contact?
Dr Jane Fletcher
jane.fletcher@uhb.nhs.uk

Trial website

www.dcode-trial.org.uk

Contact information

Type

Scientific

Primary contact

Dr Jane Fletcher

ORCID ID

http://orcid.org/0000-0001-5033-8278

Contact details

University Hospitals Birmingham
Queen Elizabeth Hospital
Mindelsohn Way
Edgbaston
Birmingham
B15 2WB
United Kingdom
+44 (0)121 371 4561
jane.fletcher@uhb.nhs.uk

Additional identifiers

EudraCT number

2018-003910-42

ClinicalTrials.gov number

NCT03718182

Protocol/serial number

40194

Study information

Scientific title

Can vitamin D supplementation in patients with Crohn's disease improve symptoms as an adjunct therapy: D-CODE feasibility study

Acronym

D-CODE Feasibility Study version 1.0

Study hypothesis

Treating vitamin D deficiency with oral supplementation in people with Crohn’s Disease may help to improve the symptoms of their disease.

Ethics approval

Newcastle and North Tyneside 2 Research Ethics Committee, NHS BT Blood Donor Centre, Holland Drive, Newcastle upon Tyne, NE2 4NQ, Tel: +44 (0)207 1048082, Email: nrescommittee.northeast-newcastleandnorthtyneside2@nhs.net, ref: 19/NE/0019 - approval pending

Study design

Randomised; Interventional; Design type: Treatment, Screening, Drug, Dietary

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Crohn's disease

Intervention

There will be two parts to the planned research involving three hospitals in Birmingham. Part 1 is a vitamin D screening study, where adults will be asked to have a finger-prick blood test to check their vitamin D levels. They will asked to answer dietary and lifestyle questions. Adults found to have vitamin D deficiency in part 1 may be invited to join part 2 of the research.

Part 2 is a vitamin D supplementation study where participants will be given a daily vitamin D capsule to take by mouth for 24 weeks. They will be randomly allocated to 2 different groups with each group receiving a different dose of vitamin D. Web randomisation will be carried out. This will be stratified by site in a ratio of 1:1.

Arm A: Fultium D3 Daily 400iu, one to be taken daily for 24 weeks
Arm B: Fultium D3 3,200iu, one to be taken daily for 12 weeks followed by Fultium D3 800iu one to be taken daily for 12 weeks.

There is no control group. Participants will have blood tests at the start,12 weeks and 24 weeks. They will complete quality of life questionnaires at the start and after 24 weeks. The last appointment will be a final follow-up appointment after 36 weeks.

Intervention type

Other

Phase

Phase IV

Drug names

Primary outcome measure

Screening studies:
25(OH) vitamin D results measured using finger-prick blood test to determine prevalence of vitamin D deficiency <50nmol/l during winter and summer months

Feasibility trial:
Feasibility assessed at the end of the trial when the final participant has had their final follow up appointment:
1. Consent rate
2. Compliance rate
3. Retention rate
4. Completion rates of efficacy outcomes
5. Adverse events

The following success criteria will be applied:
1. At least 50% of all eligible patients can be recruited and consented to join the vitamin D supplementation feasibility trial
2. At least 80% participant compliance with the intervention measured by a treatment diary.
3. Retention and follow up in at least 80% of all recruited participants at 6 months
4. Completion of all trial processes in at least 80% of recruited participants.
5. Absence of adverse reactions and causative adverse events in at least 80% of participants.

Outcomes will be either:
Feasible with no modifications
Feasible with modifications
Main study not feasible

All criteria must be met to deem the study feasible without modifications. At least criteria 1 must be met to deem the study feasible with modifications. If none of the criteria are met then the study is not feasible.

Secondary outcome measures

Outcomes that will be used to assess efficacy in future definitive trial:
Primary outcome: health related quality of life measured using the Inflammatory Bowel Disease Questionnaire (IBDQ) at baseline and 24 weeks

Overall trial start date

01/05/2018

Overall trial end date

01/06/2019

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Screening study:
1. Confirmed diagnosis of Crohn's Disease (CD)
2. > = 18 years of age
3. Written informed consent

Intervention study:
1. Confirmed diagnosis of CD
2. Identified as having Vitamin D deficiency < 50 nmol/L in the Winter screening study
3. > = 18 years of age
4. Already receiving treatment for CD as per National Institute for Health and Care Excellence (NICE) Guidance or those in remission and not currently receiving treatment but who continue to attend hospital out-patient appointments
5. Written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 300; UK Sample Size: 300

Participant exclusion criteria

Screening study:
Does not meet inclusion criteria

Intervention study:
1. Currently taking over the counter vitamin D, fish oil or multi-vitamin supplementation and unwilling to stop this to participate in the intervention study
2. Currently receiving:
2.1. Vitamin D containing supplements prescribed by a healthcare professional
2.2. Bisphosphonates
2.3. Digitalis or other cardiac glycosides
2.4. Phenytoin
2.5. Barbituates (e.g. Amylobarbitone, Butobarbitone, Methyl Phenobarbitone, Pentobarbitone, Quinalbarbitone, Amylobarbitone)
2.6. Actinomycin
2.7. Imidazole
3. With known hyperparathyroidism
4. With known sarcoidosis
5. With known renal disease or kidney stones
6. With known hypercalcaemia (corrected serum calcium > = 2.60 mmol/L)
7. With known underlying liver disease
8. With known hypersensitivity to vitamin D supplements or any of the trial medication excipients
9. Who are pregnant, breastfeeding, trying to conceive or women of child-bearing capacity who decline to have a pregnancy test where applicable and/or decline to take effective contraceptive measures during the intervention period
10. Individuals who have participated in a trial testing a medicinal product within 6 months preceding screening

Recruitment start date

01/03/2019

Recruitment end date

01/06/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University Hospitals Birmingham, Queen Elizabeth Hospital (lead site)
Mindelsohn Way Edgbaston
Birmingham
B15 2WB
United Kingdom

Trial participating centre

University Hospitals Birmingham, Birmingham Heartlands Hospital
Bordesley Green East
Birmingham
B9 5SS
United Kingdom

Trial participating centre

University Hospitals Birmingham, Good Hope Hospital
Rectory Road
Sutton Coldfield
B75 7RS
United Kingdom

Sponsor information

Organisation

University Hospitals Birmingham NHS Foundation Trust

Sponsor details

c/o Dr Chris Counsell
Queen Elizabeth Hospital Birmingham
Mindelsohn Way
Edgbaston
Birmingham
B15 2WB
United Kingdom
+44 (0)121 371 4185
chris.counsell@uhb.nhs.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

NIHR Academy; Grant Codes: ICA-CDRF-2017-03-083

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Results will be disseminated via publication and presentation at clinical and scientific conferences. In addition, the trial website will be updated in a timely manner to ensure progress reports and results are easily accessible to a wide audience. Results will be disseminated regardless of the magnitude or direction of effect.

Key target audiences are nurses and medics working in gastroenterology areas. These practitioners are key in influencing changes in everyday practice in terms of screening for vitamin D deficiency in patients with CD. Publications will include findings from:
1. Vitamin D deficiency screening and prevalence study
2. The feasibility trial
3. Patient and public involvement in the study
Publications will be in peer-reviewed journals. In order to maximise impact, journals that are most likely to be read by practitioners involved in the management of patients with CD will be selected. In addition, specific results, such as the role of vitamin D and hepcidin monitoring in the feasibility trial, will be of interest to scientists and endocrinologists who specialise in the field of vitamin D research. Publication is intended at one year after the overall trial end date

IPD sharing statement
The datasets generated during and/or analysed during the current study are not expected to be made available due to the study being a feasibility study only.

Intention to publish date

01/06/2020

Participant level data

Not expected to be available

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

22/03/2019: The condition has been changed from "Specialty: Gastroenterology, Primary sub-specialty: Inflammatory Bowel Disease; Health Category: Oral and Gastrointestinal; Disease/Condition: Noninfective enteritis and colitis" to "Crohn's disease" following a request from the NIHR.