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

Joshua Korzenik

Status and phase: Withdrawn; Phase 2

Conditions: Ulcerative Colitis

Treatments: Drug: Hydroxocobalamin with Butyrate; Drug: Placebo with Butyrate

Study type: Interventional

Funder types: Other

Identifiers

NCT04259060

2019P003412

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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0 participants in 2 patient groups, including a placebo group

Hydroxocobalamin with Butyrate

Active Comparator group

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.

Treatment:

Drug: Hydroxocobalamin with Butyrate

Placebo with Butyrate

Placebo Comparator group

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.

Treatment:

Drug: Placebo with Butyrate