Active Crohn's Disease in colon and/or terminal ileum MedDRA version: 19.0 Level: LLT Classification code 10011408 Term: Crohns disease aggravated System Organ Class: 100000004856
Conditions
Interventions
Trade Name: Dekristol 20.000 ie
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: cholecalciferol
Other descriptive name: CHOLECALCIFEROL
Sponsors
Jørgen Agnholt
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: CD patients: Age = 18 years and 5 and CRP > 8 or calprotectin > 100 mg/g CDEIS score > 5 Healthy controls: Age = 18 years and =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: CD patients: • Untreated infections, sepsis or opportunistic infections • 25-hydroxyvitamin D2 + D3 > 100 nmol/l • Biological treatment with Infliximab or Adalimumab within 3 month • Unable to talk and understand Danish • Allergy to Dekristol, peanuts or soya • Allergy to Infliximab • Infliximab antibodies detected at previous Infliximab treatment • Active or suspicion of tuberculosis infection (positive T-spot, positive quantiferon gold-test or radiological changes on thoracic x-ray) • Active and chronic viral hepatitis, present CMV or EBV infection • Hypercalcaemia and/or hypercalcuria • Pseudohypoparathyrodism • Prior calcium-containing kidney stones • Disorders of renal calcium and phosphate excretion • Treatment with benzothiadiazine derivate, phenytoin, barbiturates or digoxin • Immobilisation • Sarcoidosis • Moderate to severe heart failure (NYHA class 3 and 4) • Present or former cancer • Breastfeeding • Demyelinating diseases inclusive Guillian-Barré and Multiple Sclerosis • Vaccination with living vaccine within 4 weeks • CD with untreated abscesses • Changes in azathioprine treatment dose within 3 months • Steroid dose > 20 mg/day (prednison) or > 3 mg/day budesonide • P-sodium > 150 mmol/l • P-chloride > 106 mmol/l • Over hydration Healthy controls: • Hypercalcaemia or hypercalcuria • Ongoing infection • Known autoimmune disease • Allergy to Dekristol (cholecalciferol), peanuts or soya • Pseudohypoparathyrodism • Prior calcium-containing kidney stones • Disorders of renal calcium and phosphate excretion • Treatment with benzothiadiazine derivate, phenytoin, barbiturates or digoxin • Immobilisation • Sarcoidosis • Pregnancy or breast-feeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Mucosal T cell and macrophage VDR expression is increased by high dose vitamin D treatment and inflammation in CD compared to CD in remission and placebo. • High dose vitamin D treatment to patients with active CD down regulates the Th17 cell inflammatory cytokine production in the intestinal mucosa. • Increased VDR expression in active CD leads to an increased cathelicidin production in patients receiving vitamin D treatment. • High dose vitamin D treatment modulates the macrophage function and phenotype in mucosa. ;Secondary Objective: not applicable; Primary end point(s): Measurement of the VDR expression in mucosal T cells, DCs and macrophages before and after high dose vitamin D treatment and inflammation and compare to placebo treatment. IL-17A, IL-17F, IFN?, IL-4 and IL-22 expression in mucosal T cells before and after high dose vitamin D treatment and inflammation. Investigate whether high dose vitamin D improve the effect of TNFalpha antibody treatment on the cytokines listed above ;Timepoint(s) of evaluation of this end point: when all patients have finished the study period and the treatment is unblinded | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •HBI score, CRP and faecal calprotectin before and after high dose vitamin D treatment •The amount of dendritic cells and macrophages before and after high dose vitamin D treatment in inflamed and non-inflamed mucosa •Cathelicidin concentrations before and after treatment of inflammation •Cathelicidin concentration before and after vitamin D treatment •Correlation between vitamin D binding protein concentration, Vitamin D binding protein phenotype and 25D3 levels before and after vitamin D treatment •Correlation between VDR expression in mucosal macrophages, dendritic cells and T cells and vitamin D binding protein •Changes in phenotypes within inflammation and vitamin D treatment in T cells, macrophages and dendritic cells. •Changes in mucosal adherent bacteria measurement before and after inflammation. •Changes in phenotype and function of T cells and dendritic cells before and after treatment in PBMCs. •VDR expression and cathelicidin concentration measurements in epithelial cells • Identify the micro biome in stool samples before and after treatment and compare to healthy controls Helthy controls: • Changes in mRNA expression of vitamin D dependent genes in healthy controls treated with high dose vitamin D • VDR expression in mucosal T cells from healthy controls compared to CD patients • Cytokine production in mucosal T cells from healthy controls compared to CD patients ; Timepoint(s) of evaluation of this end point: when all patients have finished the study period and the treatment is unblinded Healthy controls: Helthy controls are included independent of the patients and the results are evaluated when all ten healthy controls are included. | — |
Countries
Denmark
Contacts
Public ContactJørgen Agnholt
Hepatology and Gastroenterology department V, Aarhus University Hospital
Outcome results
None listed