Adjunctive Treatment With Vitamin D3 in Patients With Active IBD

Study Overview
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Brief Summary
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Inflammatory bowel disease ((IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC)), is a chronic, immune-mediated disease characterized by recurrent episodes of relapse. The incidence of IBD is increasing worldwide and poses as a burden that reduces quality of life and has a significant impact on health care resources. The advent of monoclonal antibodies to tumor necrosis factor-α (anti-TNF) has revolutionized treatment of IBD, improving rates of remission and reducing hospitalizations and surgeries. Nevertheless, many patients do not adequately respond to these therapies or lose response over time. Thus, there is an important need for novel immunomodulating agents to improve our ability to achieve remission. Besides its traditional role in bone homeostasis, several studies have recognized the important role Vitamin D plays in modulating the immune response, cancer, and cardiovascular disease. Specifically, Vitamin D may mediate immunity by modulating autophagy in leukocytes and regulating the gut microbiome. Thus, Vitamin D may play an important role in IBD. Furthermore, evidence suggests that the effect of vitamin D may be mediated through the TNF-α pathway, suggesting a synergy with anti-TNF therapy. This is a randomized, double blind, placebo-controlled trial to study the effect of Vitamin D3 as an adjunct therapy for patients with active CD, UC, or IBD unspecified who are undergoing anti-TNF induction therapy.

Official Title
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Adjunctive Treatment With Vitamin D3 in Patients With Active IBD (ACTIVATED): A Randomized, Double-blind, Placebo-controlled Trial

Conditions
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IBD, Inflammatory Bowel Diseases, Crohn Disease, Ulcerative Colitis, Vitamin D3 Deficiency

Intervention / Treatment
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* Dietary Supplement: Vitamin D3
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Established diagnosis of CD, UC, or IBD-unspecified Initiating anti-TNF therapy for IBD within 2 weeks of baseline/randomization Other non-anti-TNF IBD medications must remain stable during the treatment period with the exception of tapering of corticosteroids. Recent (within 6 months) objective evidence of active IBD on colonoscopy along with elevated inflammatory markers (C-reactive protein >8 mg/L or fecal calprotectin >150 mcg/g) Current disease activity defined as a Harvey Bradshaw index > 4 at baseline (week 0) for CD subjects or Simple Clinical Colitis Activity Index > 2 at baseline (week 0) for UC subjects. Fecal Calprotectin level >150 mcg/g Exclusion Criteria: Inability to provide informed consent or unwilling or unlikely to comply with the requirements of the study. Female subjects who are pregnant, lactating, or intending to become pregnant during the study period Known intolerance or hypersensitivity to oral vitamin D3 supplementation Plasma 25(OH)D > 60 ng/mL Known celiac disease or subjects with a positive screen for celiac disease (elevated tissue transglutaminase antibodies) Serum calcium >11 mg/dL History of hyperparathyroidism History of renal calculi or chronic kidney disease Initiation of anti-TNF treatment for extra-intestinal symptoms alone Evidence of untreated infection (e.g. Clostridium difficile) History of chronic pancreatitis History of cystic fibrosis History of gastric bypass Presence of stoma or J-pouch

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D3 supplement<br>Two- 5,000 IU capsules, taken daily with a meal | Dietary Supplement: Vitamin D3<br>* Softgel capsules containing 5,000 IU cholecalciferol (Vitamin D3), sunflower oil, beef gelatin, glycerin, water<br>* Other names: cholecalciferol;|
| Placebo Comparator: Placebo<br>Two placebo capsules, taken daily with a meal | Other: Placebo<br>* Sfotgel capsules containing sunflower oil, beef gelatin, glycerin, water<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short Inflammatory Bowel Disease Questionnaire (SIBDQ) outcome | Patients will complete the SIBDQ questionnaire to measure disease activity at baseline, week 6 and week 14. | 14 weeks | 
| stool microbiome in IBD patients | Stool samples will be taken at baseline and week 14 to assess change in stool microbiome | 14 weeks | 
| serum cathelicidin levels | Serum samples will be taken at baseline and week 14 to measure serum cathelicidin levels | 14 weeks | 
| HBI | Patients with Crohn's Disease will complete the Harvey Bradshaw Index questionnaire to measure disease activity at baseline, week 6 and week 14 | 14 weeks | 
| SCCAI | Patients with Ulcerative Colitis will complete the Simple Clinical Colitis Activity Index questionnaire to measure disease activity at baseline, week 6 and week 14 | 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fecal calprotectin | Stool samples will be taken at baseline and week 14 to assess change in fecal calprotectin levels | 14 weeks | 
| plasma 25(OH)D levels. | Plasma samples will be taken at baseline and week 14 to measure 25(OH)D levels | 14 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin D3, Cholecalciferol, IBD, Inflammatory Bowel Disease, Adjunctive treatment, Crohn's Disease, Ulcerative Colitis