Hydroxocobalamin Approach for Reducing of Calprotectin With Butyrate for Ulcerative
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-Emergent Adverse Events (AE) as assessed by Common Terminology Criteria for Adverse Events (CTCAE)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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
研究组 & 干预措施
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.
干预措施: Hydroxocobalamin with Butyrate (Drug)
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.
干预措施: Placebo with Butyrate (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events (AE) as assessed by Common Terminology Criteria for Adverse Events (CTCAE)
时间窗: 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.
Change from Baseline fecal calprotectin at week 4
时间窗: At baseline and at week 4
Proportion of patients with reductions in fecal calprotectin
Clinical Symptoms assessed by Simple Clinical Colitis Activity Index (SCCAI)
时间窗: 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.
次要结局
- 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)
研究者
Joshua Korzenik
Director, Crohn's and Colitis Center
Brigham and Women's Hospital