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

• ClinicalTrials.gov Identifier: NCT04225819
• Recruitment Status: Recruiting
• First Posted: January 13, 2020
• Last Update Posted: April 6, 2022
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): Ashwin Ananthakrishnan, Massachusetts General Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
IBD; Inflammatory Bowel Diseases; Crohn Disease; Ulcerative Colitis; Vitamin D3 Deficiency	Dietary Supplement: Vitamin D3; Other: Placebo	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Adjunctive Treatment With Vitamin D3 in Patients With Active IBD (ACTIVATED): A Randomized, Double-blind, Placebo-controlled Trial
• Actual Study Start Date: October 1, 2020
• Estimated Primary Completion Date: April 1, 2023
• Estimated Study Completion Date: April 1, 2024

Arms and Interventions

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 Name: cholecalciferol
Placebo Comparator: Placebo; Two placebo capsules, taken daily with a meal	Other: Placebo; Sfotgel capsules containing sunflower oil, beef gelatin, glycerin, water

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. fecal calprotectin [ Time Frame: 14 weeks ]
   Stool samples will be taken at baseline and week 14 to assess change in fecal calprotectin levels
2. plasma 25(OH)D levels. [ Time Frame: 14 weeks ]
   Plasma samples will be taken at baseline and week 14 to measure 25(OH)D levels

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Kelly Ling; 6177247559; kling1@mgh.harvard.edu

Contact: Rachel Glasser; 6176439374; rglasser@mgh.harvard.edu

Locations

United States, Massachusetts

Massachusetts General Hospital; Recruiting

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

Investigators

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

More Information

• Responsible Party: Ashwin Ananthakrishnan, Professor of Medicine, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT04225819
• Other Study ID Numbers: 2019P003843
• First Posted: January 13, 2020
• Last Update Posted: April 6, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ashwin Ananthakrishnan, Massachusetts General Hospital:

Vitamin D3; Cholecalciferol; IBD; Inflammatory Bowel Disease; Adjunctive treatment; Crohn's Disease; Ulcerative Colitis

Additional relevant MeSH terms:

Inflammatory Bowel Diseases; Crohn Disease; Colitis; Colitis, Ulcerative; Intestinal Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Vitamin D; Cholecalciferol; Vitamins; Micronutrients; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents