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

Sponsor

Joshua Korzenik (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04259060

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ulcerative Colitis	Drug: Hydroxocobalamin with Butyrate Drug: Placebo with Butyrate	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

42 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

Double (Participant, Care Provider)

Primary Purpose:

Treatment

Official Title:

Hydroxocobalamin Approach for Reducing of Calprotectin With Butyrate for Ulcerative

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Drug: Hydroxocobalamin 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.
Placebo Comparator: 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.	Drug: Placebo 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.

Arm

Intervention/Treatment

Active Comparator: 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.

Drug: Hydroxocobalamin 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.

Placebo Comparator: 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.

Drug: Placebo 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.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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