An Open-Label, Pilot Clinical Trial To Test The Safety And Feasibility Of Intestinal Microbiota Transplantation In Patients With Chronic Heart Failure
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Study Drug Adherence
研究概览
简要总结
The purpose of this study is to determine whether people with CHF, who often have different gut bacteria from healthy, would benefit from replacing their gut bacteria with healthy donor bacteria (also known as Intestinal Microbiota Transplantation - IMT). IMT aims to restore healthy gut bacteria in patients with CHF, with previous studies showing its effectiveness, but further research is needed. IMT is an approved treatment for patients with infectious diarrhea. More than 10,000 IMTs are performed every year in the US. However IMT is not approved for patients with CHF, and thus considered investigational.
详细描述
Hypothesis
CHF is thought to be partly mediated by inflammation. The primary hypotheses are anchored in the premise that the pathophysiology of CHF is in part driven by inflammation arising from low diversity, dysbiotic intestinal microbiota through at least three mechanisms including: i) enrichment of gram- negative lipopolysaccharide (LPS) producers; ii) enrichment of organisms with uremic toxin producing potential, particularly in the setting of impaired renal functional which is common in CHF; iii) depletion of short chain fatty acid producers (SCFA) which are known to be important anti-inflammatory molecules. The investigators hypothesize that IMT therapy will increase gut diversity, reduce inflammation and improve functional capacity and biomarkers of hemodynamic stress.
Phase of Clinical Trial: 1
Study Design and Participants: Single-center, open-label study for safety and feasibility of IMT in patients with CHF. After consent, individuals of the ages 18+ with a diagnosis of CHF not due to acute myocarditis or infiltrative disease, will be enrolled to receive antibiotic preconditioning for 7 days followed by IMT daily for additional 7 days. Prior to antibiotics and IMT, recipients will be screened for inclusion/exclusion criteria, interviewed for medical history and medications, and consented. Additionally, prior to undergoing IMT and antibiotic preconditioning, baseline blood and fecal samples will be collected, and patients will undergo a six-minute walk test, echocardiogram, and quality of life questionnaire (emPHasis-10, a validated short questionnaire to assess health-related quality of life in those with CHF). Additional fecal sample would be collected following 7 days of antibiotics preconditioning and prior to initiation of active IMT therapy. Patients will undergo follow-up either by phone, video or in-person visit, or online survey of symptoms on days 1-21, and then monthly up to 6 months post-IMT to screen for serious adverse events (SAEs) and adverse events (AEs). Screening for SAEs and AEs will be done using a symptom questionnaire as well as by asking patients during our interview. Blood samples and a fecal sample will be collected from participants on months one and six post-IMT to assess circulating inflammatory mediators and to assess for changes in recipient microbiome (engraftment kinetics). At six months, patients will also undergo repeat six-minute walk test, echocardiogram, and quality of life questionnaire when logistically possible and clinically indicated.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Heart Failure with Reduced Ejection Fraction (HFrEF) or Heart Failure with Reduced Ejection Fraction (HFpEF), New York Heart Association Class II-IV
- •On stable treatment for CHF 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
- •History of celiac disease
- •Listed for transplant, and anticipated transplant listing or LVAD placement in the next 6 months
- •Acute myocarditis
- •Infiltrative and hypertrophic cardiomyopathies
- •Renal disease requiring dialysis
- •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 IMT). 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 IMT treatment. Patients will be counseled to avoid pregnancy which is the standard of care for patients with CHF.
- •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 109 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
- •Patients receiving cancer chemotherapy, immunotherapy, or radiation
研究组 & 干预措施
Participants with Chronic Heart Failure (CHF)
Antibiotic preconditioning: The antibiotic conditioning regimen will occur in the 7 days prior to IMT therapy. Antibiotic conditioning will consist of 250 mg of Vancomycin twice daily for 7 days + 500 mg of Neomycin twice daily for 7 days.
IMT dosing: A single dose consists of four, size 00 capsules of MTP-101C. An individual study participant will take the drug from a single lot only. Each lot contains microbiota separated and prepared from the stool of the individual donor and includes the dates of donation.
Each dose (four capsules) will be taken daily in the morning on an empty stomach. Clear liquids are allowed, and a regular breakfast can follow two hours later. Alternatively, the capsules can be taken after four hours of clear liquids, and no food other than clear liquids are allowed for two hours after the capsules are taken. The IMT treatment is administered for seven days. However, if the patient is hospitalized or wishes to stop the treatment, it will be stopped.
干预措施: MTP-101-C encapsulated Microbiota (Biological)
Participants with Chronic Heart Failure (CHF)
Antibiotic preconditioning: The antibiotic conditioning regimen will occur in the 7 days prior to IMT therapy. Antibiotic conditioning will consist of 250 mg of Vancomycin twice daily for 7 days + 500 mg of Neomycin twice daily for 7 days.
IMT dosing: A single dose consists of four, size 00 capsules of MTP-101C. An individual study participant will take the drug from a single lot only. Each lot contains microbiota separated and prepared from the stool of the individual donor and includes the dates of donation.
Each dose (four capsules) will be taken daily in the morning on an empty stomach. Clear liquids are allowed, and a regular breakfast can follow two hours later. Alternatively, the capsules can be taken after four hours of clear liquids, and no food other than clear liquids are allowed for two hours after the capsules are taken. The IMT treatment is administered for seven days. However, if the patient is hospitalized or wishes to stop the treatment, it will be stopped.
干预措施: Vancomycin (Drug)
Participants with Chronic Heart Failure (CHF)
Antibiotic preconditioning: The antibiotic conditioning regimen will occur in the 7 days prior to IMT therapy. Antibiotic conditioning will consist of 250 mg of Vancomycin twice daily for 7 days + 500 mg of Neomycin twice daily for 7 days.
IMT dosing: A single dose consists of four, size 00 capsules of MTP-101C. An individual study participant will take the drug from a single lot only. Each lot contains microbiota separated and prepared from the stool of the individual donor and includes the dates of donation.
Each dose (four capsules) will be taken daily in the morning on an empty stomach. Clear liquids are allowed, and a regular breakfast can follow two hours later. Alternatively, the capsules can be taken after four hours of clear liquids, and no food other than clear liquids are allowed for two hours after the capsules are taken. The IMT treatment is administered for seven days. However, if the patient is hospitalized or wishes to stop the treatment, it will be stopped.
干预措施: Neomycin (Drug)
结局指标
主要结局
Study Drug Adherence
时间窗: Day 14
Study drug adherence (compliance) will be measured as the number of participants taking 100% (all doses) of the IMT.
Number of Adverse Events
时间窗: Day 180
Safety will be measured by the number of adverse events that occur in participants.
次要结局
未报告次要终点
研究者
Melana Yuzefpolskaya, MD
Associate Professor of Medicine
Columbia University