Ulcerative Colitis, Ulcerative Colitis Mild
Conditions
Brief summary
This study is a clinical trial being done to investigate the efficacy of drug BRS201 as a treatment in patients with active mild ulcerative colitis. Participation in this study will take 12 weeks long and the study is structured as a crossover study in which participants will take the study drug for 4 weeks and a placebo drug for 4 weeks in a randomized order in the form of an oral medication. Participation may also involve receiving an IV dose of the medication. The study will require participants to attend 7 study visits, all of which will be conducted at a study site. Participation will involve taking an oral medication twice daily, tracking the medication in a log, and getting blood drawn and giving a stool and urine sample for a few lab tests throughout the study.
Interventions
DRUGBRS201
Groups 1, 2, 3, and 4 will all contain 5 subjects each, with each subject receiving active study drug and placebo in a 3:2 randomized order; 3 will receive active treatment for the first for four weeks followed by placebo for four weeks, while the remaining 2 will receive placebo for four weeks followed by active treatment for four weeks.
DRUGPlacebo
Groups 1, 2, 3, and 4 will all contain 5 subjects each, with each subject receiving active study drug and placebo in a 3:2 randomized order; 3 will receive active treatment for the first for four weeks followed by placebo for four weeks, while the remaining 2 will receive placebo for four weeks followed by active treatment for four weeks.
Sponsors
Brigham and Women's Hospital
Mercy Medical Center
Dartmouth-Hitchcock Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This is a double-blinded study.
Intervention model description
This is a crossover study in which each participant will receive active medication for a period of time and placebo for a period of time.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Ability to give consent * Patients with a confirmed diagnosis of UC for \> 3 months * History of ≥ 15 cm of colonic involvement as confirmed by colonoscopy * Disease activity based on calprotectin \> 200 * Allowed medications: mesalamine and sulfasalazine * Patients with primary sclerosing cholangitis are eligible to enroll
Exclusion criteria
* History of uncontrolled hypertension with systolic BP \> 140 and systolic BP \> 90 * Chronic kidney disease as defined by GFR \<55mL/min * Impaired hepatic function (transaminases elevated \> 2.5 x ULN) unless due to PSC * Evidence of C. difficile (Negative test result within 1 month is acceptable) * Infectious Colitis or drug induced colitis * Crohn's Disease or Indeterminate colitis * Decompensated liver disease * Patients who are pregnant or breastfeeding * Use of rectal therapies * Patients who have a confirmed malignancy or cancer within 5 years * Congenital or acquired immunodeficiencies * Other comorbidities including: Diabetes mellitus, systemic lupus * High likelihood of colectomy in the next 2 months * Participation in a therapeutic clinical trial in the preceding 30 days or simultaneously during this trial * Patients with a history or risk of cardiovascular conditions, including arrhythmia, long QT syndrome, congestive heart failure, stroke, or coronary artery disease * Prohibited medications: Vitamin C, prednisone, immune modulators (including but not limited to azathioprine, 6-mercaptopurine, mycophenolate mofetil, tacrolimus, cyclosporine, thalidomide, interleukin-10, interleukin-11, and Omvoh or mirikizumab-mrkz) and biologics within the past six weeks including anti-TNF agents within the past six weeks, vedolizumab within the past six weeks, ustekinumab Risankizumab), a JAKi (tofacitinib or upadacitinib), or Velsipity (etrasimod) within the past 6 weeks. (The aim is to treat people who are having disease activity and just on mesalamine.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction of H2S metabolites in plasma | 4 weeks | The primary endpoint for this study is the capacity of study drug to reduce metabolites of H2S in plasma from baseline (week 0) compared to the end of active treatment (4 weeks) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Simple Clinical Colitis Activity Index (SCCAI) | 12 weeks | Clinical symptoms assessed by SCCAI which measures patient reported outcomes on a scale of 0 to 19, where a higher score indicates more severe activity and active disease is a score of 5 or more. |
| Plasma nitrite, nitrate, or nitrosothiol | 8 weeks | Correlation between changes in plasma nitrite, nitrate or nitrosothiol levels and fecal calprotectin |
| Normalization of fecal calprotectin lab measurements | 4 weeks | The primary endpoint for this study is the capacity of study drug to normalize fecal calprotectin levels from baseline (week 0) compared to end of active treatment (4 weeks). |
| Change in fecal calprotectin lab measurements | 4 weeks | Change in fecal calprotectin to \< ULN at the end of active treatment |
| Partial Mayo score | 4 weeks | Change in partial Mayo scores from baseline to end of active treatment. The partial Mayo score measures disease activity on a scale of 0 to 9, where a higher score indicates more severe disease activity and a score of 1 or less indicated remission. |
| Measurement of sulfur metabolites in urine | 8 weeks | Analysis of urine for measurement of thiosulfate, thiocyanate, nitrate and nitrite |
Countries
United States
Contacts
CONTACTJoshua Korzenik, MD
CONTACTSiani Ellis
Outcome results
None listed