Clinical trial NCT04259060: Hydroxocobalamin Approach for Reducing of Calprotectin With Butyrate for Ulcerative Colitis Remission
Official title: Hydroxocobalamin Approach for Reducing of Calprotectin With Butyrate for Ulcerative
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Ulcerative Colitis
Keywords: Ulcerative Colitis
Inflammatory Bowel Disease
Butyrate
Hydroxocobalamin
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2020-02-06
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from Baseline fecal calprotectin at week 4
timeFrame: At baseline and at week 4
measure: Incidence of Treatment-Emergent Adverse Events (AE) as assessed by Common Terminology Criteria for Adverse Events (CTCAE)
timeFrame: Up to 4 weeks
measure: Clinical Symptoms assessed by Simple Clinical Colitis Activity Index (SCCAI)
timeFrame: Up to 4 weeks
Secondary outcomes:
measure: Assessment of urinary and plasma nitrite, nitrate levels and nitrosothiol levels
timeFrame: At week 1-2 and at week 4
measure: Normalization of fecal calprotectin below the upper limit of normal
timeFrame: At the end of week 4
measure: Reduction of Mayo Score (Phase 2)
timeFrame: At the end of week 4
measure: Correlation between urinary and plasma nitrite, nitrate or nitrosothiol levels and fecal calprotectin
timeFrame: Up to 4 weeks
Other outcomes:
Locations:
city: Chestnut Hill
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Joshua R Korzenik, MD
role: PRINCIPAL_INVESTIGATOR
References: