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

Phase 2

Withdrawn

• Conditions: Ulcerative Colitis
• Interventions: Drug: Hydroxocobalamin with Butyrate; Drug: Placebo with Butyrate

• Registration Number: NCT04259060
• Lead Sponsor: Joshua Korzenik

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.

Study Timeline

• Study First Submitted: 2020-01-27
• Study First Submitted QC: 2020-02-04
• Study First Posted: 2020-02-06
• Status Verified: 2023-04
• Study Start: 2024-01
• Last Update Submitted: 2024-04-19
• Last Update Posted: 2024-04-22
• Primary Completion: 2025-08
• Study Completion: 2025-10

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Hydroxocobalamin with Butyrate	Hydroxocobalamin with Butyrate	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.
Placebo with Butyrate	Placebo with Butyrate	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.

Primary Outcome Measures

Name	Time	Method
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.
Change from Baseline fecal calprotectin at week 4	At baseline and at week 4	Proportion of patients with reductions in fecal calprotectin
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 Outcome Measures

Name	Time	Method
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
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
Correlation between urinary and plasma nitrite, nitrate or nitrosothiol levels and fecal calprotectin	Up to 4 weeks	Comparison of biochemical levels with calprotectin

Trial Locations

Locations (1)

Brigham and Women's Hospital; 🇺🇸 Chestnut Hill, Massachusetts, United States