Adjunctive Treatment With Vitamin D3 in Patients With Active IBD (ACTIVATED)

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

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.

Study Overview

• Status: Suspended
• Conditions: Inflammatory Bowel Diseases; Crohn Disease; Ulcerative Colitis; IBD; Vitamin D3 Deficiency
• Intervention / Treatment: Dietary supplement: Vitamin D3; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kelly Ling; Phone Number: 6177247559; Email: kling1@mgh.harvard.edu
• Study Contact Backup: Name: Rachel Glasser; Phone Number: 6176439374; Email: rglasser@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Ashwin Ananthakrishnan, MD, MPH, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: January 3, 2020
• First Submitted That Met QC Criteria: January 8, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Ulcerative Colitis; Inflammatory Bowel Disease; Vitamin D3; IBD; Crohn's Disease; Cholecalciferol; Adjunctive treatment
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Inflammatory Bowel Diseases; Crohn Disease; Intestinal Diseases; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: 2019P003843

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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