Clinical trial NCT04225819: Adjunctive Treatment With Vitamin D3 in Patients With Active IBD
Official title: Adjunctive Treatment With Vitamin D3 in Patients With Active IBD (ACTIVATED): A Randomized, Double-blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: NA
Conditions: IBD
Inflammatory Bowel Diseases
Crohn Disease
Ulcerative Colitis
Vitamin D3 Deficiency
Keywords: Vitamin D3
Cholecalciferol
IBD
Inflammatory Bowel Disease
Adjunctive treatment
Crohn's Disease
Ulcerative Colitis
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2020-01-13
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Short Inflammatory Bowel Disease Questionnaire (SIBDQ) outcome
timeFrame: 14 weeks
measure: stool microbiome in IBD patients
timeFrame: 14 weeks
measure: serum cathelicidin levels
timeFrame: 14 weeks
measure: HBI
timeFrame: 14 weeks
measure: SCCAI
timeFrame: 14 weeks
Secondary outcomes:
measure: fecal calprotectin
timeFrame: 14 weeks
measure: plasma 25(OH)D levels.
timeFrame: 14 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Ashwin Ananthakrishnan, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: