Selenium Supplementation in Moderate-Severely Active Ulcerative Colitis Patients Treated With Advanced Therapies: A Placebo-Controlled, Double-Blind, Randomized Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- Clinical Remission
研究概览
简要总结
Micronutrient deficiencies are common in ulcerative colitis (UC). Selenium deficiency is associated with worse disease outcomes including disease flares and need for surgery. Previous in vitro and in vivo studies demonstrated that selenium regulates colonic inflammation, and that selenium supplementation protects against DSS-induced colitis. In this proof-of-concept clinical trial, we aim to test the hypothesis that selenium supplementation in moderate to severely active UC patients will improve responsiveness to advanced therapy such as biologics and small molecules.
详细描述
Ulcerative colitis (UC) is an immune-mediated inflammatory condition of the colon characterized by mucosal inflammation and bloody diarrhea. UC affects over 1 million Americans with a rapidly growing international prevalence. The primary driver of disease impact in UC is uncontrolled inflammation and disease flares with downstream effects related to disease complications, including lower quality of life, hospitalizations, surgery, and development of colon cancer. Micronutrients exert a critical influence on immune responses, and micronutrient deficiencies have been linked to immune mediated inflammation. Micronutrient deficiencies are common in UC patients, even during periods of quiescent disease. Deficiency of one micronutrient in particular, selenium, is associated with an increased risk for disease flare and need for surgery in UC.
Given selenium is a naturally occurring micronutrient found in many foods and sold over the counter as a dietary supplement or as part of multi-vitamin supplements, demonstration of its efficacy as a supplement in UC would offer an opportunity to better guide the use of these in routine practice through nutritional counseling and optimization of disease outcomes with minimal additive risk. Patients enrolled in the study will either receive 200 mcg selenomethionine daily or a placebo supplement daily depending on their randomization group. Daily selenomethionine or placebo. The supplementation should begin within 1 week of the first dose of the advanced therapy initiation for UC.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Known or newly diagnosed moderate to severe UC (as defined by the modified Mayo score of 5-9; confirmed by clinical, endoscopic, and/or histopathological evidence prior to screening as per standard of care) who are either being started on or are being switched to a different FDA approved advanced therapy
- •The acceptable list of advanced therapies is (anti-TNF, anti-IL23, anti-integrin). For example, anti-tumor necrosis factor - infliximab, adalimumab, golimumab, certolizumab; anti-IL12/23 - ustekinumab, mirikizumab, risakizumab, guselkumab; anti-integrin - vedolizumab
- •Mayo endoscopic sub-score ≥2 (moderate to severe)
- •Mayo rectal bleeding sub-score ≥1 (moderate to severe)
- •Mayo stool frequency sub-score ≥2 (moderate to severe)
- •Age 18-85 and able to fully participate in all aspects of the trial
排除标准
- •Pediatric patients defined by being younger than 18 years of age
- •Patients who are currently pregnant, expecting to participate in getting pregnant during the study period through natural or assisted techniques (in-vitro fertilization, intra-uterine insemination, intracytoplasmic sperm injection, embryo transfer, planned egg or sperm donor), or are currently lactating.
- •Women with childbearing potential will be required to use highly effective birth control if not surgically sterile or postmenopausal for ≥ 2 years for the duration of the active intervention period. Highly effective forms of birth control include those that alone or in combination result in a low failure rate (i.e., less than 1 percent per year) when used consistently and correctly. This would include combined pill and progestin-only pill, evra patch, nuvaring, depo-provera, paragard, mirena, implanon, female sterilization, male sterilization.
- •The criteria for being considered postmenopausal would be the following: twelve months of spontaneous amenorrhea or; six months of spontaneous amenorrhea with serum FSH levels 40 mIU/mL or; six weeks post-surgical bilateral oophorectomy with or without hysterectomy.
- •Male subjects are considered of reproductive potential unless surgically sterile (e.g., vasectomy) and should not participate in activities of reproductive potential other than heterosexual intercourse (e.g., they should not participate in in-vitro fertilization or other reproductive assistance techniques) during the active intervention period of 12 weeks. Male subjects of reproductive potential that have female partners of reproductive potential should commit to the use of recommended contraception in the partnership during the active intervention period of 12 weeks, and be informed of the recommendations for pregnancy screening during the intervention phase of the trial. Additionally, male subjects (regardless of reproductive potential) that have partners that are currently pregnant should commit to condom use during intercourse to prevent transmission of the drug product through semen during the active intervention period of 12 weeks.
- •If participants become pregnant during the intervention period, they will be withdrawn to avoid risks to the fetus. If participants become pregnant during the follow-up observational period, they will be permitted to remain in the study as no active intervention is being administered. Research related assessments and visits will be tailored to those recommended during pregnancy by the treating provider(s).
- •Medical conditions that may predispose to toxicity including a history of type 2 diabetes mellitus, hypothyroidism, acute or chronic kidney disease, history of kidney transplant, history of infertility.
- •Abnormal baseline labs for renal function, thyroid function, or hepatic function: Renal function panel including creatinine (results should fall within normal lab reference ranges below 1.3 mg/dL for males and 1.1 mg/dL for females). Thyroid function tests with thyroid stimulating hormone (TSH; results should fall within normal lab reference ranges of 0.5 to 5.0 mIU/L). Hepatic function panel (results should fall within normal lab reference ranges) including alanine aminotransaminase (below 55 U/L for males and 45 U/L for females), aspartate aminotransferase (below 40 U/L for males and 32 U/L for females), total bilirubin (below 1.2 mg/dL), direct bilirubin (below 0.3 mg/dL), alkaline phosphatase (below 120 IU/L for males and 104 IU/L for females).
- •Any patient taking blood thinners, cholesterol-lowering drugs, antioxidants, warfarin, or any other immune system-dependent medications that may interact with selenium. Specifically, they should not be taking any of the following: alendronate, baloxavir marboxil, cinoxacin, ciprofloxacin, deferiprone, delafloxacin, dimercaprol, eltrombopag, enoxacin, etidronate, gatifloxacinm gemifloxacin, grepafloxacin, ibandronate, levofloxacin, lomefloxacin, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, patiromer, penicillamine, risedronate. sodium polystyrene sulfonate, sparfloxacin. tiludronate, trientine, trovafloxacin, vadadustat
- •Allergies to components/compounds used to formulate selenium or placebo supplements.
- •Known or suspected diagnosis of Crohn's colitis, indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, microscopic colitis or infectious colitis (Clostridium difficile, cytomegalovirus (CMV), any other pathogenic illness felt by the investigator to be the source of colitis).
- •Concern for impending need for hospitalization or urgent colectomy as determined by the treating provider(s) and/or investigator performing screening/evaluation for enrollment.
- •Unwillingness or inability to be compliant with selenium supplementation, adjustments in diet if necessary, or complete study-related visits/biospecimen collection.
研究组 & 干预措施
Selenium supplementation
Participants enrolled in the active intervention group will be taking a single daily dose of 200 mcg selenomethionine for 12 weeks
干预措施: Selenium supplementation (Drug)
Placebo
Participants enrolled in the placebo group will be taking a placebo supplement once daily for 12 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Clinical Remission
时间窗: Week 12
Modified Mayo score of 0-2 with a rectal bleeding sub-score of 0 and endoscopic sub-score of 0-1
次要结局
- Endoscopic improvement(Week 12)
- Endoscopic remission(Week 12)
- Mucosal healing(Week 12)
- Numeric Urgency Rating(Week 12)
- Fecal calprotectin(Week 12)
- Rectal bleeding(Week 12)
- Stool frequency(Week 12)
- Modified Mayo Score(Week 12)
研究者
Parambir Dulai
Associate Professor of Medicine
Northwestern University