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.
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)
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.
Parallel
Selenium supplementation
DrugPatients enrolled in the study will receive 200 mcg selenomethionine daily
Placebo
DrugThe placebo group will be taking a placebo supplement once daily
Clinical Remission
Modified Mayo score of 0-2 with a rectal bleeding sub-score of 0 and endoscopic sub-score of 0-1
Endoscopic improvement
Mayo endoscopic sub-score of 0-1
Endoscopic remission
Mayo endoscopic sub-score of 0
Mucosal healing
Mayo endoscopic sub-score of 0-1 and Geboes histology score ≤ 2
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)
Adverse Events
Any AE occurring after randomization
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
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Northwestern University
Lead sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborator
