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

Ulcerative Colitis Clinical Trial

— HARBOUR  

Official title:

Hydroxocobalamin Approach for Reducing of Calprotectin With Butyrate for Ulcerative

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04259060
• Other study ID #: 2019P003412
• Status: Withdrawn
• Phase: Phase 2
• Start date: January 2024
• Est. completion date: October 2025

Study information

• Verified date: April 2023
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 2025
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

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 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.

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Chestnut Hill	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Joshua Korzenik

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline fecal calprotectin at week 4	Proportion of patients with reductions in fecal calprotectin	At baseline and at week 4
Primary	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
Primary	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	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
Secondary	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
Secondary	Reduction of Mayo Score (Phase 2)	Proportion of patients with a reduction in Mayo Score	At the end of week 4
Secondary	Correlation between urinary and plasma nitrite, nitrate or nitrosothiol levels and fecal calprotectin	Comparison of biochemical levels with calprotectin	Up to 4 weeks