Adjunctive Treatment With Vitamin D3 in Patients With Active IBD (ACTIVATED): A Randomized, Double-blind, Placebo-controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 暂停
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- serum cathelicidin levels
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Vitamin D3 supplement
Two- 5,000 IU capsules, taken daily with a meal
干预措施: Vitamin D3 (Dietary Supplement)
Placebo
Two placebo capsules, taken daily with a meal
干预措施: Placebo (Other)
结局指标
主要结局
serum cathelicidin levels
时间窗: 14 weeks
Serum samples will be taken at baseline and week 14 to measure serum cathelicidin levels
HBI
时间窗: 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
Short Inflammatory Bowel Disease Questionnaire (SIBDQ) outcome
时间窗: 14 weeks
Patients will complete the SIBDQ questionnaire to measure disease activity at baseline, week 6 and week 14.
stool microbiome in IBD patients
时间窗: 14 weeks
Stool samples will be taken at baseline and week 14 to assess change in stool microbiome
SCCAI
时间窗: 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
次要结局
- fecal calprotectin(14 weeks)
- plasma 25(OH)D levels.(14 weeks)
研究者
Ashwin Ananthakrishnan
Professor of Medicine
Massachusetts General Hospital