Hydroxocobalamin Approach for Reducing of Calprotectin With Butyrate for Ulcerative Colitis Remission

Study Overview
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Brief Summary
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This is a 4-week pilot, multicenter, randomized, double-blinded placebo controlled trial of hydroxocobalamin and butyrate in ulcerative colitis (UC) that will occur in two phases. The main objectives of this study are to determine the capacity of hydroxocobalamin and butyrate to reduce calprotectin in those with inflammatory disease in UC to determine the safety and preferential dose of hydroxocobalamin with butyrate in UC.

Detailed Description
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The goal of this study is to determine the preferable dose of hydroxocobalamin in a 4-week pilot study in patients with UC and determine if this approach can reduce stool calprotectin. Before going forward with a larger efficacy trial, the investigators are first aiming to determine if the supplements/medications we are proposing to use are sufficient to reduce a biomarker. Consequently, this study will look at a more easily measurable biomarker to provide evidence that the dosing is sufficient. This pilot study will be conducted to assess preferable dose of hydroxocobalamin based on reduction of calprotectin. The investigators aim to determine if this reduction is sustained over time and is correlated to changes in clinical disease activity.

Official Title
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Hydroxocobalamin Approach for Reducing of Calprotectin With Butyrate for Ulcerative

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Hydroxocobalamin with Butyrate
* Drug: Placebo with Butyrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 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 Partial Mayo score of > 4 for phase one or a total Mayo score > 5 in phase 2 Patients with primary sclerosing cholangitis are eligible to enroll Exclusion Criteria: History of uncontrolled hypertension with a systolic BP > 140 and a systolic BP > 90 Chronic kidney disease as defined by a GFR <60mL/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 to confirm Infectious Colitis or drug induced colitis Crohn's Disease or Indeterminate colitis Decompensated liver disease Patients who are pregnant or breastfeeding Prohibited medications: Vitamin C, prednisone, immune modulators (including but not limited to azathioprine, 6-mercaptopurine, mycophenolate mofetil, tacrolimus, cyclosporine, thalidomide, interleukin-10 and interleukin-11) and anti-TNF agents within the past six weeks Use of rectal therapies Patients who have a confirmed malignancy or cancer within 5 years Participation in a therapeutic clinical trial in the preceding 30 days or simultaneously during this trial Congenital or acquired immunodeficiencies Other comorbidities including: Diabetes mellitus, systemic lupus Patients with a history of kidney stones Patients with a history or risk of cardiovascular conditions, including arrhythmia, long QT syndrome, congestive heart failure, stroke, or coronary artery disease High likelihood of colectomy in the next 2 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hydroxocobalamin with Butyrate<br>Subjects enrolled will take hydroxocobalamin capsules twice daily for 4 weeks. All subjects will take an oral butyrate dose of 120 mg twice daily for 4 weeks. | Drug: Hydroxocobalamin with Butyrate<br>* In phase 1, patients will take hydroxocobalamin at 1g daily for four weeks. This will be in the form of 1 500mg capsule twice a day. Butyrate will be 240 mg daily in a divided dose (120 mg twice daily) which is 5 pills twice a day. In phase 2, the dose of hydroxocobalamin will be increased to 2g daily (1g twice a day) for four weeks pending FDA approval. Butyrate will remain at 240 mg daily in a divided dose (120 mg twice daily) which is 5 pills twice a day. Patients will undergo flexible sigmoidoscopy at baseline and at week four in phase 2.<br>|
| Placebo Comparator: Placebo with Butyrate<br>Subjects enrolled will take placebo capsules twice daily for 4 weeks. All subjects will take an oral butyrate dose of 120 mg twice daily for 4 weeks. | Drug: Placebo with Butyrate<br>* In phase 1, patients will take 1 placebo capsule twice a day. Butyrate will be taken at 240 mg daily in a divided dose (120 mg twice daily) which is 5 pills twice a day. In phase 2, patients will take 2 placebo capsules twice a day, along with butyrate at 240 mg daily in a divided dose (120 mg twice daily) which is 5 pills twice a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline fecal calprotectin at week 4 | Proportion of patients with reductions in fecal calprotectin | At baseline and at week 4 | 
| Incidence of Treatment-Emergent Adverse Events (AE) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) | CTCAE are a set of criteria for the standardized classification of adverse effects of drugs used in clinical trials. It uses a range of grades from 1 to 5, where 1 is mild and 5 is life-threatening.The number of AE and grade of each AE will be measured for the duration of the trial. | Up to 4 weeks | 
| Clinical Symptoms assessed by Simple Clinical Colitis Activity Index (SCCAI) | The SCCAI is an index to measure disease activity in patients with UC. SCCAI will be used throughout the trial to measure clinical UC symptoms of participants. | Up to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of urinary and plasma nitrite, nitrate levels and nitrosothiol levels | Comparison of levels at baseline to week 1-2 and week 4 | At week 1-2 and at week 4 | 
| Normalization of fecal calprotectin below the upper limit of normal | Assessment in number of patients whose fecal calprotectin normalizes | At the end of week 4 | 
| Reduction of Mayo Score (Phase 2) | Proportion of patients with a reduction in Mayo Score | At the end of week 4 | 
| Correlation between urinary and plasma nitrite, nitrate or nitrosothiol levels and fecal calprotectin | Comparison of biochemical levels with calprotectin | Up to 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ulcerative Colitis, Inflammatory Bowel Disease, Butyrate, Hydroxocobalamin