A Study of Fecal Microbiota Transplantation (FMT) for the Treatment of Recurrent C. Difficile Associated Diarrhea (RCDAD) Via Retention Enema or Oral Route
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 69
- 试验地点
- 2
- 主要终点
- Safety as Assessed by Number of Participants With Any Adverse Events (AE)s
研究概览
简要总结
The objective of the study is to investigate the safety of a frozen or lyophilized inoculum administered, respectively, by retention enema or capsules in patients with recurrent C. difficile associated diarrhea (RCDAD).
This is a single center, randomized, parallel assignment, open label safety study conducted in subjects with RCDAD. Fifty subjects will be enrolled in the study and randomized at 1:1 ratio to receive frozen filtered intestinal bacteria via retention enema or lyophilized donor intestinal bacteria. All subjects will be followed for a total of 3 years after study completion.
Donors will be enrolled and screened at the laboratory in the Center for Infectious Diseases at University of Texas School of Public Health (UT-SPH). The donors will come from a variety of places, including the UT-SPH. At least 20 donors will be screened to recruit at least 15 qualified donors.
Recipients may self-refer but must have a physician who agrees to accept care of the patient following fecal microbiota transplantation (FMT). Subjects consenting to treatment at Baylor St. Luke's Medical Center (BSLMC) and the UT-SPH must be willing to self-pay for the FMT in the amount of $1,500. There will be no insurance accepted. Subjects undergoing retention enema will be treated as outpatients at either at BSLMC, Kelsey-Seybold Clinic, or at the Memorial Hermann in the Texas Medical Center. All subjects taking capsules with lyophilized intestinal bacteria will be seen at UT-SPH. Once the procedure is completed, the recipient's care will be returned to their physician. At least 75 recipients will be screened to recruit 50 qualified recipients.
The primary endpoint is to evaluate the safety of FMT by rectal or oral routes with secondary endpoint related to efficacy prevention of RCDAD. In order to monitor any health effects for safety, participants will be contacted pre- and 7, 14, 30 days, then monthly basis for the first 90 days after FMT and quarterly till 3 years after FMT. The following procedures will be completed: review recipient diary with the recipient to ensure that the following information is recorded correctly and a fresh stool sample will be collected from recipient, tested for C. difficile toxins and an aliquot (2mL) stored at -80C for microbiome analysis. Recipients will be contacted by phone for their diarrhea status on monthly basis till 90 days after FMT, then on quarterly basis till 3 years after FMT.
详细描述
Clinical improvement is monitored by telephone/email and or E-mail up to 3 years after FMT. Minor clinical management of the subject with over the counter medication (e.g. loperamide, acetaminophen and Saccharomyces boulardii [probiotic]) will be performed in the case of mild diarrhea and abdominal pain.
All subjects will be followed up by phone the day after FMT to assess health status during week one. Study subjects will be monitored on approximately days 7, 14 and 30, monthly for the first 3 month and quarterly for 3 years after FMT, at which time the recipient diary will be reviewed with the recipient to review any adverse experience or medication taken since the medical history obtained at FMT.
Investigators should determine if any adverse experience or medication need to be further studied. Donor will be contacted and tested if it is necessary. All actions will be recorded on with medical condition, dates of adverse experience and medication taken, indication for new medication taken, and total daily dose.
Recipients should be instructed at FMT to contact the Investigator if they have any questions regarding adverse experience or the appropriateness of a medication after FMT.
The following definitions of terms are guided by the International Conference of Harmonization and US Code of Federal Regulations (21 CFR 312.32).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
frozen intestinal bacteria from a healthy donor given by retention enema or lyophilized intestinal bacteria given orally in capsules for therapy in subjects with recurrent C. difficile associated diarrhea (RCDAD)
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
- •Male and female subjects 18 years of age or older
- •Sexually active female subjects of child-bearing potential must agree to use an effective method of birth control during the treatment and follow-up period
- •Required to sign an informed consent form
- •Subject"s attending physician agrees to provide care following FMT
- •Able to follow study procedures and follow-ups.
- •Diagnosed by medical history of ≥ 3 RCDAD bouts in outpatients or ≥ 2 bouts of RCDAD in an inpatient with ≥ 2 positive fecal tests for C. difficile toxin
- •Received at least one course of adequate antibiotic therapy for CDAD (≥ 10 days of vancomycin, metronidazole or fidaxomicin) after the subjects last bout of CDAD
排除标准
- •Subjects with known neutropenia with absolute neutrophil count <0.5 x 109/L
- •Evidence of toxic megacolon, fulminant colitis, gastrointestinal perforation, ileus, abdominal distension, lack of bowel sounds, fever, or hypotension
- •Known peripheral white blood cell count > 15.0 x 109/L or temperature > 38.0 °C
- •Diarrhea due to definable non-CDAD pathogen
- •Post total colectomy or presence of a colostomy
- •Unable to tolerate FMT via enema for any reason
- •Requiring systemic non-C. difficile antibiotic therapy at the time of FMT
- •Actively taking Saccharomyces boulardii or other probiotic at the time of FMT
- •Need for continuing use of oral vancomycin, oral or IV metronidazole, fidaxomicin, rifaximin or nitazoxanide at the time of FMT
- •Severe underlying disease such that the patient is not expected to survive for one or more years or unstable medical condition requiring daily change in treatments
研究组 & 干预措施
Frozen Microbiota
Donor stool (greater than 150 grams) was collected <4 hours prior to the procedure and then mixed in a homogenizer with 750mL, 1:5 dilution sterilized 0.9% NaCl in a large sterilized suction canister until a smooth consistency was reached. The suspension was filtered using a coffee filter twice. The microbiota suspension (750mL) was kept at -80C labeled with ID and expiration date which was 6 months after preparation. Intervention - Frozen Microbiota will be delivered via enema
干预措施: Frozen Microbiota (Biological)
Lyophilized Microbiota
Lyophilized Microbiota_Donor stool (greater than 150 grams) was collected <4 hours prior to the procedure and then mixed in a homogenizer with 750mL, 1:5 dilution sterilized 0.9% NaCl in a large sterilized suction canister until a smooth consistency was reached. The suspension was filtered using a coffee filter twice. The microbiota suspension (750mL) was starting lyophilization process within 30 minutes after completion of stool filtration. Lyophilized microbiota products were kept at 4C and were used within 6 months after preparation. Intervention - Lyophilized Microbiota will be delivered orally
干预措施: Lyophilized Microbiota (Biological)
结局指标
主要结局
Safety as Assessed by Number of Participants With Any Adverse Events (AE)s
时间窗: 6 months after the procedure
any untoward medical occurrence associated with the use of PRIM-DJ2727 whether or not considered drug related is considered as an adverse event (AE)
次要结局
- Number of Participants Who Continue to Have Diarrhea and C. Difficile Toxin Following Fecal Microbiota Transplantation From a Healthy Donor(60 days after the procedure)
研究者
Zhi-Dong Jiang
associate professor
The University of Texas Health Science Center, Houston