Ulcerative Colitis
Conditions
Keywords
Ulcerative Colitis, Inflammatory Bowel Disease, Butyrate, Hydroxocobalamin
Brief summary
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
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.
Interventions
DRUGHydroxocobalamin with Butyrate
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.
DRUGPlacebo with Butyrate
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.
Sponsors
Joshua Korzenik
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-75 2. Ability to give consent 3. Patients with a confirmed diagnosis of UC for \> 3 months 4. History of \> 15 cm of colonic involvement as confirmed by colonoscopy 5. Disease activity based on calprotectin \> 200 6. Allowed medications: mesalamine and sulfasalazine 7. Partial Mayo score of \> 4 for phase one or a total Mayo score \> 5 in phase 2 8. Patients with primary sclerosing cholangitis are eligible to enroll
Exclusion criteria
1. History of uncontrolled hypertension with a systolic BP \> 140 and a systolic BP \> 90 2. Chronic kidney disease as defined by a GFR \<60mL/min 3. Impaired hepatic function (transaminases elevated \> 2.5 x ULN) unless due to PSC 4. Evidence of C. difficile - negative test result within 1 month is acceptable to confirm 5. Infectious Colitis or drug induced colitis 6. Crohn's Disease or Indeterminate colitis 7. Decompensated liver disease 8. Patients who are pregnant or breastfeeding 9. 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 10. Use of rectal therapies 11. Patients who have a confirmed malignancy or cancer within 5 years 12. Participation in a therapeutic clinical trial in the preceding 30 days or simultaneously during this trial 13. Congenital or acquired immunodeficiencies 14. Other comorbidities including: Diabetes mellitus, systemic lupus 15. Patients with a history of kidney stones 16. Patients with a history or risk of cardiovascular conditions, including arrhythmia, long QT syndrome, congestive heart failure, stroke, or coronary artery disease 17. High likelihood of colectomy in the next 2 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline fecal calprotectin at week 4 | At baseline and at week 4 | Proportion of patients with reductions in fecal calprotectin |
| Incidence of Treatment-Emergent Adverse Events (AE) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) | Up to 4 weeks | 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. |
| Clinical Symptoms assessed by Simple Clinical Colitis Activity Index (SCCAI) | Up to 4 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of urinary and plasma nitrite, nitrate levels and nitrosothiol levels | At week 1-2 and at week 4 | Comparison of levels at baseline to week 1-2 and week 4 |
| Correlation between urinary and plasma nitrite, nitrate or nitrosothiol levels and fecal calprotectin | Up to 4 weeks | Comparison of biochemical levels with calprotectin |
| Normalization of fecal calprotectin below the upper limit of normal | At the end of week 4 | Assessment in number of patients whose fecal calprotectin normalizes |
| Reduction of Mayo Score (Phase 2) | At the end of week 4 | Proportion of patients with a reduction in Mayo Score |
Countries
United States
Outcome results
None listed