Study of Novel Therapeutics for Acute Remedy of Colitis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Sulfur Metabolism
研究概览
简要总结
This study is a clinical trial being done to investigate the efficacy of drug BRS201 as a treatment in patients with acute ulcerative colitis. Patients who qualify are adults who have not responded to treatments for their severe ulcerative colitis. Participation in this study will take 12 weeks long and the study is structured as an open-label pilot study in which participants will take the study drug for 4 weeks in the form of an oral medication. Participation may also involve receiving an IV dose of the medication. The study will require participants to attend 8 study visits, all of which will be conducted at a study site. Participation will involve taking an oral medication twice daily, tracking the medication in a log, and getting blood drawn and giving a stool and urine sample for a few lab tests throughout the study. Participants may also undergo a flexible sigmoidoscopy at the beginning and end of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Severe outpatient or hospitalized for an acute UC flare
- •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
- •Patients with primary sclerosing cholangitis are eligible to enroll
- •Patients will have failed 5 days of oral prednisone 30 mg or greater for 5 days and still having a SCCAI of > 6
- •Patients who are taking 20mg or less of oral prednisone and plan to stay at that dose during their participation in the study
- •Accepted medications:
- •Anti-TNF agents are permissible if the patient has been taking them for at least 10 weeks and anticipates to maintain a steady for the duration of the study.
- •Rinvoq (Upadacitinib) is permissible if the subject has been taking this medication for at least 4 weeks and anticipates to maintain a steady dose for the duration of the study.
- •Xeljanz (Tofacitinib) is permissible if the subject has been taking this medication for at least 4 weeks and anticipates to maintain a steady dose for the duration of the study.
- •Other biologics are permissible if the subject has been taking the medication for at least 10 weeks and anticipates to maintain a steady dose for the duration of the study
排除标准
- •History of uncontrolled hypertension with systolic BP > 140 and systolic BP > 90
- •Chronic kidney disease as defined by GFR <55mL/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)
- •Infectious Colitis or drug induced colitis
- •Crohn's Disease or Indeterminate colitis
- •Decompensated liver disease
- •Patients who are pregnant or breastfeeding
- •Patients who have a confirmed malignancy or cancer within 5 years
- •Congenital or acquired immunodeficiencies
- •Other comorbidities including: Diabetes mellitus, systemic lupus
- •Participation in a therapeutic clinical trial in the preceding 30 days or simultaneously during this trial
- •Patients with a history or risk of cardiovascular conditions, including arrhythmia, long QT syndrome, congestive heart failure, stroke, or coronary artery disease
- •Prohibited medications:
- •Rinvoq (Upadacitinib): Subjects will be excluded from this study if their last dose of this medication was administered within 4 weeks. If subjects have stopped taking this medication and their last dose was administered more than 4 weeks prior to enrollment, they will be eligible for participation.
- •Xeljanz (Tofacitinib): Subjects will be excluded from this study if their last dose of this medication was administered within 4 weeks. If subjects have stopped taking this medication and their last dose was administered more than 4 weeks prior to enrollment, they will be eligible for participation.
- •Other Medications: Subjects will be excluded from this study if they stopped taking any other medications for ulcerative colitis within 8 weeks. If subjects have stopped taking the medication and their last dose was more than 8 weeks prior to enrollment, they will be eligible for participation.
研究组 & 干预措施
BRS201 Arm
In Group 1 of the study, subjects will take oral study drug at 1.2g daily, PO with 120mg oral butyrate twice daily (240mg daily) for 4 weeks.
In Group 3 of the study, subjects will take oral study drug at 1.2g twice daily, PO (2.4g daily) with 120mg oral butyrate twice daily (240mg daily) for 4 weeks.
In Group 3 of the study, subjects will take oral study drug at 1.2g twice daily, PO (2.4g daily) with 120mg oral butyrate twice daily (240mg daily) for 4 weeks. Subjects will also receive a one time 2.5g dose of study drug at initiation.
In Group 4 of the study, subjects will repeat the previous conditions of the group that proves to be the most effective. Subjects in Group 4 will undergo two flexible sigmoidoscopies, one at screening and one at week 4.
干预措施: BRS201 (Drug)
结局指标
主要结局
Sulfur Metabolism
时间窗: 4 weeks
The primary measure of dose response will be urinary measures of sulfur metabolism including a \> 50% reduction from pretreatment levels sulfate, and thiosulfate.
次要结局
- Plasma nitrite, nitrate, or nitrosothiol(8 weeks)
- Reduction in fecal calprotectin lab measurements(4 weeks)
- Mitochondria evaluation(12 weeks)
- Simple Clinical Colitis Activity Index (SCCAI)(12 weeks)
- Normalization of fecal calprotectin lab measurements(8 weeks)
- Mayo Score(4 weeks)
- Tissue Analysis(4 weeks)
- Urine Assays(12 weeks)
研究者
Joshua Korzenik
MD-Director, Brigham and Women's Hospital Crohn's and Colitis Center
Brigham and Women's Hospital