Ulcerative ColitisPhase 2HARBOURNCT04259060
Hydroxocobalamin Approach for Reducing of Calprotectin With Butyrate for Ulcerative Colitis Remission
A Phase 2 study testing Hydroxocobalamin with Butyrate in people with Ulcerative Colitis, run by Joshua Korzenik at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- Hydroxocobalamin with Butyrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2024to Oct 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Chestnut Hill, Massachusetts, 02467
About this study
Official title: Hydroxocobalamin Approach for Reducing of Calprotectin With Butyrate for Ulcerative
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.
Read the 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.
- Conditions
- Ulcerative Colitis
- Being tested
- Hydroxocobalamin with Butyrate, Placebo with Butyrate
- Keywords
- Ulcerative Colitis, Inflammatory Bowel Disease, Butyrate, Hydroxocobalamin
- Medical subject headings
- Colitis, Ulcerative, Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydroxocobalamin with ButyrateDrug
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 ButyrateDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo with Butyrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline fecal calprotectin at week 4
Proportion of patients with reductions in fecal calprotectin
Measured: 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.
Measured: 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.
Measured: Up to 4 weeks
Secondary outcomes (4)
Assessment of urinary and plasma nitrite, nitrate levels and nitrosothiol levels
Comparison of levels at baseline to week 1-2 and week 4
Measured: At week 1-2 and at week 4
Normalization of fecal calprotectin below the upper limit of normal
Assessment in number of patients whose fecal calprotectin normalizes
Measured: At the end of week 4
Reduction of Mayo Score (Phase 2)
Proportion of patients with a reduction in Mayo Score
Measured: At the end of week 4
Correlation between urinary and plasma nitrite, nitrate or nitrosothiol levels and fecal calprotectin
Comparison of biochemical levels with calprotectin
Measured: Up to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2020
- Study startJan 2024 (estimated)
- Primary completionAug 2025 (estimated)
- Study completionOct 2025 (estimated)
Why it stopped: Decision to pursue a smaller scale pilot study instead
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joshua Korzenik
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Joshua Korzenik, Brigham and Women's Hospital
- Investigators
- Joshua R Korzenik, MD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04259060
- Sponsor's protocol ID
- 2019P003412
- Acronym
- HARBOUR
- Status last verified
- Apr 2023
- First submitted
- 27 Jan 2020
- Last updated
- 22 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hydroxocobalamin Approach for Reducing of Calprotectin With Butyrate for Ulcerative
- ClinicalTrials.gov ID
- NCT04259060
- Acronym / sponsor ID
- HARBOUR / 2019P003412
- Conditions
- Ulcerative Colitis
- Keywords
- Ulcerative Colitis, Inflammatory Bowel Disease, Butyrate, Hydroxocobalamin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Decision to pursue a smaller scale pilot study instead
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Joshua KorzenikUniversity, hospital or other
- Study start
- Jan 2024 (estimated)
- Primary completion
- Aug 2025 (estimated)
- Study completion
- Oct 2025 (estimated)
- First posted
- 6 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hydroxocobalamin with Butyrate | Active comparator | Drug: Hydroxocobalamin with ButyrateSubjects 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. |
| Placebo with Butyrate | Placebo comparator | Drug: Placebo with ButyrateSubjects 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydroxocobalamin with ButyrateIn 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. | Drug | Hydroxocobalamin with Butyrate |
| Placebo with ButyrateIn 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. | Drug | Placebo with Butyrate |
Primary outcome
Change from Baseline fecal calprotectin at week 4
Time frame: At baseline and 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)
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.
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.
4 secondary outcomes
Assessment of urinary and plasma nitrite, nitrate levels and nitrosothiol levels
Time frame: At week 1-2 and at week 4
Normalization of fecal calprotectin below the upper limit of normal
Time frame: At the end of week 4
Reduction of Mayo Score (Phase 2)
Time frame: At the end of week 4
Correlation between urinary and plasma nitrite, nitrate or nitrosothiol levels and fecal calprotectin
Time frame: Up to 4 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joshua R Korzenik, MD principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hydroxocobalamin with Butyrate in people with Ulcerative Colitis, run by Joshua Korzenik at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 22 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from Baseline fecal calprotectin at week 4 (time frame: At baseline and at week 4). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2024.