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

NCT04259060 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 2019P003412
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Ulcerative Colitis

Keywords

Ulcerative Colitis; Inflammatory Bowel Disease; Butyrate; Hydroxocobalamin

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• Assessment of urinary and plasma nitrite, nitrate levels and nitrosothiol levels

  At week 1-2 and at week 4

• Normalization of fecal calprotectin below the upper limit of normal

  At the end of week 4

• Reduction of Mayo Score (Phase 2)

  At the end of week 4

• Correlation between urinary and plasma nitrite, nitrate or nitrosothiol levels and fecal calprotectin

  Up to 4 weeks

Study Arms (2)

Hydroxocobalamin with Butyrate

ACTIVE COMPARATOR

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

Placebo with Butyrate

PLACEBO COMPARATOR

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

Interventions

Hydroxocobalamin with Butyrate DRUG

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.

Hydroxocobalamin with Butyrate

Placebo with Butyrate DRUG

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.

Placebo with Butyrate

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Joshua Korzenik: lead

Study Sites (1)

Brigham and Women's Hospital

Chestnut Hill, Massachusetts, 02467, United States

Location

MeSH Terms

Conditions

Colitis, Ulcerative; Inflammatory Bowel Diseases

Interventions

Hydroxocobalamin; Butyrates

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Vitamin B 12; Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Joshua R Korzenik, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Crohn's and Colitis Center

Study Record Dates

• First Submitted: January 27, 2020
• First Posted: February 6, 2020
• Study Start: January 1, 2024
• Primary Completion: August 1, 2025
• Study Completion: October 1, 2025
• Last Updated: April 22, 2024

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)