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

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ClinicalTrials.gov Identifier: NCT04259060
Recruitment Status : Not yet recruiting
First Posted : February 6, 2020
Last Update Posted : March 18, 2022
Sponsor:
Information provided by (Responsible Party):
Joshua Korzenik, Brigham and Women's Hospital

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Study Start Date : January 2023
Estimated Primary Completion Date : January 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine


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.





Primary Outcome Measures :
  1. Change from Baseline fecal calprotectin at week 4 [ Time Frame: At baseline and at week 4 ]
    Proportion of patients with reductions in fecal calprotectin

  2. Incidence of Treatment-Emergent Adverse Events (AE) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: 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.

  3. Clinical Symptoms assessed by Simple Clinical Colitis Activity Index (SCCAI) [ Time Frame: 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 :
  1. Assessment of urinary and plasma nitrite, nitrate levels and nitrosothiol levels [ Time Frame: At week 1-2 and at week 4 ]
    Comparison of levels at baseline to week 1-2 and week 4

  2. Normalization of fecal calprotectin below the upper limit of normal [ Time Frame: At the end of week 4 ]
    Assessment in number of patients whose fecal calprotectin normalizes

  3. Reduction of Mayo Score (Phase 2) [ Time Frame: At the end of week 4 ]
    Proportion of patients with a reduction in Mayo Score

  4. Correlation between urinary and plasma nitrite, nitrate or nitrosothiol levels and fecal calprotectin [ Time Frame: Up to 4 weeks ]
    Comparison of biochemical levels with calprotectin



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04259060


Contacts
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Contact: Fernanda Quevedo 617-732-9173 squevedo@bwh.harvard.edu
Contact: Joshua Korzenik, MD 617-732-9173 jkorzenik@bwh.harvard.edu

Locations
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United States, Massachusetts
Brigham and Women's Hospital
Chestnut Hill, Massachusetts, United States, 02467
Contact: Fernanda Quevedo    617-732-9173    sfernandaquevedo@bwh.harvard.edu   
Principal Investigator: Joshua Korzenik, MD         
Sponsors and Collaborators
Joshua Korzenik
Investigators
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Principal Investigator: Joshua R Korzenik, MD Brigham and Women's Hospital
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Responsible Party: Joshua Korzenik, Director, Crohn's and Colitis Center, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT04259060    
Other Study ID Numbers: 2019P003412
First Posted: February 6, 2020    Key Record Dates
Last Update Posted: March 18, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Joshua Korzenik, Brigham and Women's Hospital:
Ulcerative Colitis
Inflammatory Bowel Disease
Butyrate
Hydroxocobalamin
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Hydroxocobalamin
Vitamin B 12
Hematinics
Vitamin B Complex
Vitamins
Micronutrients
Physiological Effects of Drugs