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

Hydroxocobalamin Approach for Reducing of Calprotectin With Butyrate for Ulcerative

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.

Study Overview

• Status: Withdrawn
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Hydroxocobalamin with Butyrate; Drug: Placebo with Butyrate

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 Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Chestnut Hill, Massachusetts, United States, 02467
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Joshua Korzenik
• Investigators: Principal Investigator: Joshua R Korzenik, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: January 27, 2020
• First Submitted That Met QC Criteria: February 4, 2020
• First Posted (Actual): February 6, 2020

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Ulcerative Colitis; Inflammatory Bowel Disease; Butyrate; Hydroxocobalamin
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Vitamin B 12; Hydroxocobalamin
• Other Study ID Numbers: 2019P003412

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No