Selenium Supplementation in Moderate-Severely Active Ulcerative Colitis Patients Treated With Advanced Therapies (Selenium-UC)

Selenium Supplementation in Moderate-Severely Active Ulcerative Colitis Patients Treated With Advanced Therapies: A Placebo-Controlled, Double-Blind, Randomized Clinical Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Ulcerative Colitis (UC)
• Intervention / Treatment: Drug: Selenium supplementation; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Libeth Rosas, MPH; Phone Number: 312-503-0006; Email: libeth.rosas@northwestern.edu
• Study Contact Backup: Name: Diego Jimenez Lara; Phone Number: 312-503-4126; Email: diego.jimenez@northwestern.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
      • Contact: Parambir S. Dulai, MD; Email: parambir.dulai@northwestern.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Selenium supplementation; Participants enrolled in the active intervention group will be taking a single daily dose of 200 mcg selenomethionine for 12 weeks	Drug: Selenium supplementation; Patients enrolled in the study will receive 200 mcg selenomethionine daily
Placebo Comparator: Placebo; Participants enrolled in the placebo group will be taking a placebo supplement once daily for 12 weeks	Drug: Placebo; The placebo group will be taking a placebo supplement once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Remission	Modified Mayo score of 0-2 with a rectal bleeding sub-score of 0 and endoscopic sub-score of 0-1	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endoscopic improvement	Mayo endoscopic sub-score of 0-1	Week 12
Endoscopic remission	Mayo endoscopic sub-score of 0	Week 12
Mucosal healing	Mayo endoscopic sub-score of 0-1 and Geboes histology score ≤ 2	Week 12
Numeric Urgency Rating	Score ranges from 0-10 ; higher scores are worse	Week 12
Fecal calprotectin	Continuous measure	Week 12
Rectal bleeding	Proportion of participants with any improvement in rectal bleeding score from baseline (any reduction in Mayo rectal bleeding sub-score, the Mayo rectal bleeding sub-score ranges from 0-3; a higher score indicates more blood seen)	Week 12
Stool frequency	Proportion of participants with any improvement in stool frequency score from baseline (any reduction in Mayo stool frequency sub-score, Mayo stool frequency sub-score ranges from 0-3; higher score indicates more abnormality in stool frequency)	Week 12
Modified Mayo Score	Sum of Mayo rectal bleeding sub-score, Mayo stool frequency sub-score, and Mayo endoscopic sub-score (score ranges from 0-9, a higher score indicates more severe disease)	Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Any AE occurring after randomization	Week 12
Selenium Toxicity	Any AE that is potentially related to selenium toxicity as assessed by blood selenium levels being outside of acceptable range with accompanying symptoms known to be associated with excess selenium intake	Week 12

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: February 15, 2026
• First Submitted That Met QC Criteria: February 15, 2026
• First Posted (Actual): February 23, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: ulcerative colitis; colitis; selenium supplementation; selenomethionine
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: STU00224383; R01DK144103 (U.S. NIH Grant/Contract)

Drug and device information, study documents

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