Cholecalciferol in Chronic Inflammatory Bowel Diseases (5C)

Cholecalciferol Comedication in Patients With Chronic Inflammatory Bowel Diseases (Crohn's Disease or Ulcerative Colitis) - the 5C-study

In this research project, the investigators want to find out whether the additional intake of vitamin D further reduces the inflammatory events in the intestines of IBD patients. There are three groups of subjects: the 1st group takes a capsule of 24,000 IU per week, the 2nd group takes 24,000 IU per month, the 3rd group is the control group. The intake extends over 6 months during the autumn and winter period.

Study Overview

• Status: Recruiting
• Conditions: IBD
• Intervention / Treatment: Drug: D3 VitaCaps®

Detailed Description

Inflammatory bowel diseases (IBD) are a chronic immunologically mediated inflammatory condition of the gastrointestinal tract comprising two clinical entities: ulcerative colitis and Crohn's disease. Genetic,environmental and microbial factors, and the immune responses play an important role in the disease development. The incidence and prevalence of IBD have increased in the past 50 years in the Western world and are increasing in developing countries. Faecal calprotectin is a reliable biomarker for functional quantitative measurement of intestinal inflammation in IBD. Faecal calprotectin test is recognized to be reliable in clinical practice for the assessment of endoscopic activity and remission. Vitamin D or cholecalciferol is a prohormone classified as a fat-soluble vitamin. The organism can produce the substance itself in the skin during summer time. The importance of vitamin D for the regulation of calcium metabolism, for bone formation, for the treatment of osteoporosis and for the prevention of falls and associated fractures is generally recognized. Vitamin D seems to play a role in the pathogenesis of many diseases,including IBD. Several observational studies showed an inverse correlation between 25(OH)D and disease activity. Vitamin D deficiency is common among patients with IBD. The relapse rate in patients with Crohn' disease and 25(OH)D <50 nmol/l is almost doubled. There is a significant inverse correlation between serum 25(OH)D levels and the specific inflammatory marker faecal calprotectin. The lowest serum 25(OH)D levels have been reported in patients with a more severe disease progression or previous ileum resection. Low 25(OH)D serum concentrations are associated with more frequent IBDassociated surgeries and hospitalisations. However, no intervention studies have been conducted to date that have investigated the influence of vitamin D on inflammation in adult IBD patients. An intervention study with subjects aged 5-18 years nevertheless showed a statistically significant inverse correlation between 25(OH)D serum concentration and the inflammation marker calprotectin.

The FOPH Expert Commission recommends a daily intake of 600 IU for adults aged 19-59 years, 800 IU for >60 years. The maximum tolerable intake for all age groups is 4'000 IU daily, with daily or cumulative intermittent, weekly or monthly, administration being considered. Adherence is, however, better with intermittent intake. In this study, the administration to patients with monthly supplementation represents one capsule per month, corresponding to 800 IU cholecalciferol daily. The administration to patients with weekly supplementation is one capsule per week, corresponding to 3,500 IU cholecalciferol daily. The cumulative administration of 24'000 IU per week does not exceed the upper limit of 4'000 IU per day or 28'000 IU per week. Insufficient adherence to IBD medication has been identified as responsible for therapy escalation with more expensive regimens, disease complication or hospitalization, that all drive substantial costs. In a systematic review including 93'998 patients with IBD, adherence rate to prescribed biologics ranged from 37% to 96%. Difficulties with medication adherence can be identified with indirect methods such as questionnaires. To monitor adherence, questionnaires and pill-count are the most frequently used methods. However, more robust methods are recommended such as electronic methods. One option is the use of a e-pill bottles with electronic caps. The opening of the e-pill-bottle that corresponds to the withdrawal of a medicine from the container is registered with a time stamp, a method currently in development in our research group.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Petr Hrúz, Prof. Dr.; Phone Number: +41 61 777 74 19; Email: petr.hruz@clarunis.ch
• Study Contact Backup: Name: Jean-Pierre Rothen, Dr.; Phone Number: +41 61 207 61 75; Email: jp.rothen@unibas.ch

Study Locations

• Switzerland
  • Basel, Switzerland, 4002
    • Recruiting
    • Clarunis University Center for Gastrointestinal and Liver Diseases
    • Contact: Petr Hrúz, Prof. Dr.; Phone Number: 0041 61 77 77 575; Email: petr.hruz@clarunis.ch
    • Contact: Jean-Pierre Rothen, Dr.; Phone Number: 0041 61 207 61 75; Email: jp.rothen@unibas.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed IBD diagnosis; Age ≥ 18 years

Exclusion Criteria:

• Hypercalcaemia defined as serum calcium value >2.70 mmol/l; Hyperparathyreoidism defined as serum iPTH value >65 ng/l; Hypoparathyreoidism defined as serum iPTH value <15 ng/l; Renal insufficiency defined as eGFR < 30 ml/min; Anamnesis of: Propensity to form calcium-containing kidney stones, Impaired renal calcium or phosphate excretion, Sarcoidosis; Pregnancy or lactation; Supplementation of vitamin D >200 IU/d (5μg/d) during study period; Administration of products that have a potential interaction with cholecalciferol, e.g. phenytoin, rifampicin, barbiturates, actinomycin, imidazole-antifungals

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; no treatment
Active Comparator: Weekly; weekly administration of one capsule, corresponding to approximately 3'500 IU cholecalciferol daily.	Drug: D3 VitaCaps®; Gelatine free soft capsules containing 24'000 IU cholecalciferol per capsule; Other Names: Vitamin D
Active Comparator: Monthly; monthly administration of one capsule, corresponding to approximately 800 IU cholecalciferol daily.	Drug: D3 VitaCaps®; Gelatine free soft capsules containing 24'000 IU cholecalciferol per capsule; Other Names: Vitamin D

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Faecal calprotectin value	Reduction of the faecal calprotectin value after 6 months.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CRP serum levels	Change in CRP serum levels after 6 months.	6 months
Vitamin D levels	Increase in vitamin D levels after 6 months.	6 months
Disease-specific activity score	Change in disease-specific activity score after 6 months.	6 months
Adherence to the comedication	Adherence to the comedication with the vitamin D capsules	6 months

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Petr Hrúz, Prof. Dr., Clarunis University Center for Gastrointestinal and Liver Diseases

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: November 14, 2022
• First Submitted That Met QC Criteria: November 14, 2022
• First Posted (Actual): November 22, 2022

Study Record Updates

• Last Update Posted (Actual): December 1, 2022
• Last Update Submitted That Met QC Criteria: November 28, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: EKNZ 2022-00899

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No