A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- donor engraftment comparison
研究概览
简要总结
This pilot clinical trial will evaluate the initial safety, feasibility, and pharmacokinetics of microbiota transplant therapy (MTT) with antibiotic pre-conditioning and fiber supplementation vs. placebo in patients with pulmonary arterial hypertension (PAH). This trial will inform development of future trials of MTT as a treatment for PAH. 24 PAH patients will be randomized to receive either MTT with antibiotic preconditioning + fiber supplementation, MTT with antibiotic preconditioning + placebo supplementation, or placebo + placebo supplementation. MTT will in a capsule form composed of freeze-dried, encapsulated intestinal microbiota from healthy donors. Fiber supplementation will be 10-14 gm oral fiber supplement. Patients will be followed at week 1, week 2, week 4, week 12, and week 24. Patient will undergo stool sample collection at baseline, week 1, week 4, and week 12, blood sample collection at baseline, week 4, and week,12. In addition, patient will undergo an echocardiogram, six-minute walk test (6MWT) and quality of life questionnaire at baseline and at week 12.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Double (Participant, Outcomes Assessor)
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
- •Provision of signed and dated consent form
- •Ages 18-75
- •Diagnosis of PAH
- •On stable treatment for PAH for one month prior to enrollment
- •Able to swallow capsules
- •Able to provide blood sample and fecal sample
- •Stated willingness to comply with all study procedures and availability for the duration of trial to follow-up by telephone, in-person, email, and/or video visits or correspondence.
排除标准
- •Dysphagia to pills
- •Clinically active inflammatory bowel disease
- •Pregnancy or breastfeeding. A pregnancy test will be obtained from females of child- bearing potential at the screening visit or day 1 (prior to the receipt of MTT). Patients with a positive pregnancy test will be excluded. A negative result will be required for subjects who are females of child-bearing potential to receive MTT. Patients will be counseled to avoid pregnancy which is the standard of care for patients with PAH.
- •Life expectancy of < 6 months
- •Presence of ileostomy or colostomy
- •Patients on immunosuppressants (calcineurin inhibitors, prednisone ≥ 20 mg/day, methotrexate, azathioprine, immunosuppressive biologics, JAK inhibitors).
- •Patients with neutropenia (an absolute neutrophil count < 0.5 x 10 9 cells/L) obtained on a complete blood count with differential at screening
- •History of solid organ or bone marrow transplant
- •Anticipated recurrent antibiotic use (patients with frequent urinary tract infections or sinusitis)
- •History of severe anaphylactic food allergy
- •History of celiac disease
- •Patients receiving cancer chemotherapy, immunotherapy, or radiation
- •Patients with severe Irritable bowel syndrome (IBS) defined by an IBS score >250
研究组 & 干预措施
Drug group
PAH patients randomized to MTT with antibiotic preconditioning + fiber supplementation
干预措施: MTT with antibiotic preconditioning + fiber supplementation (Drug)
Control 1
MTT with antibiotic preconditioning + placebo supplementation
干预措施: MTT with antibiotic preconditioning + placebo supplementation (Drug)
Control 2
placebo + placebo supplementation.
干预措施: MTT with placebo + placebo supplementation. (Other)
结局指标
主要结局
donor engraftment comparison
时间窗: week 12
The difference in donor microbiota engraftment between the three study groups at week 12
次要结局
- safety of MTT with antibiotic preconditioning and fiber supplementation in patients with PAH(week 12)
- change in inflammatory markers(week 12)
- compare right ventricular function, measure 1(week 12)
- feasibility of MTT with antibiotic preconditioning and fiber supplementation in patients with PAH(week 12)
- compare right ventricular function(week 12)