Back to resultsHydroxocobalamin Approach for Reducing of Calprotectin With Butyrate for Ulcerative Colitis Remission (HARBOUR)
Primary Purpose
Ulcerative Colitis
Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Hydroxocobalamin with Butyrate
Placebo with Butyrate
Sponsored by
About this trial
This is an interventional treatment trial for Ulcerative Colitis focused on measuring Ulcerative Colitis, Inflammatory Bowel Disease, Butyrate, Hydroxocobalamin
Eligibility Criteria
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
Sites / Locations
- Brigham and Women's Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Hydroxocobalamin with Butyrate
Placebo with Butyrate
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Change from Baseline fecal calprotectin 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)
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)
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
Comparison of levels at baseline to week 1-2 and week 4
Normalization of fecal calprotectin below the upper limit of normal
Assessment in number of patients whose fecal calprotectin normalizes
Reduction of Mayo Score (Phase 2)
Proportion of patients with a reduction in Mayo Score
Correlation between urinary and plasma nitrite, nitrate or nitrosothiol levels and fecal calprotectin
Comparison of biochemical levels with calprotectin
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04259060
Brief Title
Hydroxocobalamin Approach for Reducing of Calprotectin With Butyrate for Ulcerative Colitis Remission
Acronym
HARBOUR
Official Title
Hydroxocobalamin Approach for Reducing of Calprotectin With Butyrate for Ulcerative
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
January 2024 (Anticipated)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
October 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Joshua Korzenik
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ulcerative Colitis
Keywords
Ulcerative Colitis, Inflammatory Bowel Disease, Butyrate, Hydroxocobalamin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
42 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Hydroxocobalamin with Butyrate
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo with Butyrate
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Hydroxocobalamin with Butyrate
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo with Butyrate
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change from Baseline fecal calprotectin at week 4
Description
Proportion of patients with reductions in fecal calprotectin
Time Frame
At baseline and at week 4
Title
Incidence of Treatment-Emergent Adverse Events (AE) as assessed by Common Terminology Criteria for Adverse Events (CTCAE)
Description
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.
Time Frame
Up to 4 weeks
Title
Clinical Symptoms assessed by Simple Clinical Colitis Activity Index (SCCAI)
Description
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.
Time Frame
Up to 4 weeks
Secondary Outcome Measure Information:
Title
Assessment of urinary and plasma nitrite, nitrate levels and nitrosothiol levels
Description
Comparison of levels at baseline to week 1-2 and week 4
Time Frame
At week 1-2 and at week 4
Title
Normalization of fecal calprotectin below the upper limit of normal
Description
Assessment in number of patients whose fecal calprotectin normalizes
Time Frame
At the end of week 4
Title
Reduction of Mayo Score (Phase 2)
Description
Proportion of patients with a reduction in Mayo Score
Time Frame
At the end of week 4
Title
Correlation between urinary and plasma nitrite, nitrate or nitrosothiol levels and fecal calprotectin
Description
Comparison of biochemical levels with calprotectin
Time Frame
Up to 4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Charu Madhwani Jain, MBBS, MPH
Phone
6177329119
Email
cmjain@bwh.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Joshua Korzenik, MD
Phone
617-732-9173
Email
jkorzenik@bwh.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joshua R Korzenik, MD
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Chestnut Hill
State/Province
Massachusetts
ZIP/Postal Code
02467
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Charu Madhwani Jain, MBBS, MPH
Phone
617-732-9119
Email
cmjain@bwh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Marin Waddington
Phone
6177329451
Email
mwaddington@bwh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Joshua Korzenik, MD
12. IPD Sharing Statement
Plan to Share IPD
No
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Hydroxocobalamin Approach for Reducing of Calprotectin With Butyrate for Ulcerative Colitis Remission
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