A Study of Microbiome Transplantation for the Treatment of Constipation and/or Significant Bloating in Patients With Systemic Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Change in Pelvic Floor Distress as Assessed by the Pelvic Floor Distress Inventory Questionnaire-20 (POPDI-6 subscale score)
研究概览
简要总结
The purpose of this study is to characterize the intestinal flora in subjects with systemic sclerosis-related constipation and/or significant bloating and to determine safety and trends in improvements in the diversity of colonic microbiome and patient symptoms following the administration of either frozen or lyophilized PRIM-DJ2727 microbiota.
详细描述
The purpose of this study is to evaluate the tolerability and safety of frozen and lyophilized microbiome transplant product (PRIM- DJ2727), to characterize the microbiome (α-diversity and β-diversity) and metabolome in patients with Systemic Sclerosis (SSc)-related constipation and/or significant bloating, to examine improvement in constipation and/or significant bloating after microbiome transplant, to examine improved colonic transit after microbiome transplant, to examine subjective global improvement and improvement in SSc disease characteristics, to monitor change in concentration of systemic and fecal inflammatory markers, and to monitor for change in fecal short-chain fatty acids and metabolome.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Are seen in the UT Houston Scleroderma Center (UTHSC)
- •Meet 2013 American college of rheumatology (ACR)/European league against rheumatism (EULAR) criteria or CREST criteria for SSc
- •Meet Rome IV criteria for constipation and/or significant bloating
- •Subject willing to sign an informed consent form
- •Subject deemed likely to survive for ≥ 1 year after enrollment
- •Able to follow study procedure and follow-up
- •Sexually active male and female subjects of childbearing potential must agree to use an effective method of birth control during the treatment and follow-up period
- •Female subjects of childbearing potential must have a negative pregnancy test in the 72 hours before the procedure
- •Subjects who agree to adhere to a stable diet for at least 4 weeks before joining the study and throughout the study
- •Subjects must have an attending physician who will provide non-transplant care for the subject
排除标准
- •Subjects with constipation and/or significant bloating from causes not attributed to SSc as determined by the treating physician (e.g., inflammatory bowel disease, medication, significant diabetes, or hypothyroidism, etc.)
- •Subjects unwilling to stop taking probiotic supplements during the duration of the study
- •Subjects that have post-total or hemicolectomy or the presence of a colostomy
- •Subjects unable to tolerate microbiome transplant via enema for any reason or swallow capsules
- •Subjects requiring systemic antibiotic therapy 4 weeks before the study
- •If subjects are on immunosuppression, the immunosuppression dose should be stable for at least 4 weeks before study enrollment
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
PRIM-DJ2727
干预措施: PRIM-DJ2727 (Drug)
结局指标
主要结局
Change in Pelvic Floor Distress as Assessed by the Pelvic Floor Distress Inventory Questionnaire-20 (POPDI-6 subscale score)
时间窗: pre-transplant, post-treatment within weeks 11 to 12
The Pelvic Floor Distress Inventory Questionnaire-20 (PFDI-20) is composed of 3 subscales: the Urinary Distress Inventory-6 (UDI-6), the Pelvic Organ Prolapse Distress Inventory-6 (POPDI-6), and the Colorectal-Anal Distress Inventory-8 (CRADI-8). For each question, the participant must indicate how much bowl, bladder, or pelvic symptoms have been bothering them in the past 3 months on a 4-point scale that ranges from "not at all" (0) to "quite a bit" (4). Total score for each subscale ranges from 0 to 100, with a higher score indicating worse distress. The sum of the 3 subscales are added together to get the PFDI-20 summary score, which ranges from 0 to 300, with a higher score indicating worse distress.
Change in symptoms and signs of constipation and/or significant bloating as assessed by total score on the University of California, Los Angeles Gastrointestinal Tract Questionnaire, version 2.0 (UCLA GIT 2.0)
时间窗: pre-transplant, post-treatment within weeks 11 to 12
This consists of 34 questions covering domains such as diarrhea, constipation, abdominal pain, nausea, bloating, gastroesophageal reflux, fecal incontinence, and emotional well-being related to GI symptoms. Each item is scored on a Likert scale ranging from 0 to 3 (0 = none, 1 = mild, 2 = moderate, 3 = severe), with higher scores indicating greater symptom severity. Domain scores are calculated as the sum of responses to items within the domain, and a total score is calculated by summing all domain scores, representing the overall GI symptom burden. Total score will be reported, and the total score ranges from 0-102.
Change in Pelvic Floor Distress as Assessed by the Pelvic Floor Distress Inventory Questionnaire-20 (PFDI-20 summary score)
时间窗: pre-transplant, post-treatment within weeks 11 to 12
The Pelvic Floor Distress Inventory Questionnaire-20 (PFDI-20) is composed of 3 subscales: the Urinary Distress Inventory-6 (UDI-6), the Pelvic Organ Prolapse Distress Inventory-6 (POPDI-6), and the Colorectal-Anal Distress Inventory-8 (CRADI-8). For each question, the participant must indicate how much bowl, bladder, or pelvic symptoms have been bothering them in the past 3 months on a 4-point scale that ranges from "not at all" (0) to "quite a bit" (4). Total score for each subscale ranges from 0 to 100, with a higher score indicating worse distress. The sum of the 3 subscales are added together to get the PFDI-20 summary score, which ranges from 0 to 300, with a higher score indicating worse distress.
Change in Pelvic Floor Distress as Assessed by the Pelvic Floor Distress Inventory Questionnaire-20 (UDI-6 subscale score)
时间窗: pre-transplant, post-treatment within weeks 11 to 12
The Pelvic Floor Distress Inventory Questionnaire-20 (PFDI-20) is composed of 3 subscales: the Urinary Distress Inventory-6 (UDI-6), the Pelvic Organ Prolapse Distress Inventory-6 (POPDI-6), and the Colorectal-Anal Distress Inventory-8 (CRADI-8). For each question, the participant must indicate how much bowl, bladder, or pelvic symptoms have been bothering them in the past 3 months on a 4-point scale that ranges from "not at all" (0) to "quite a bit" (4). Total score for each subscale ranges from 0 to 100, with a higher score indicating worse distress. The sum of the 3 subscales are added together to get the PFDI-20 summary score, which ranges from 0 to 300, with a higher score indicating worse distress.
Change in Pelvic Floor Distress as Assessed by the Pelvic Floor Distress Inventory Questionnaire-20 (CRADI-8 subscale score)
时间窗: pre-transplant, post-treatment within weeks 11 to 12
The Pelvic Floor Distress Inventory Questionnaire-20 (PFDI-20) is composed of 3 subscales: the Urinary Distress Inventory-6 (UDI-6), the Pelvic Organ Prolapse Distress Inventory-6 (POPDI-6), and the Colorectal-Anal Distress Inventory-8 (CRADI-8). For each question, the participant must indicate how much bowl, bladder, or pelvic symptoms have been bothering them in the past 3 months on a 4-point scale that ranges from "not at all" (0) to "quite a bit" (4). Total score for each subscale ranges from 0 to 100, with a higher score indicating worse distress. The sum of the 3 subscales are added together to get the PFDI-20 summary score, which ranges from 0 to 300, with a higher score indicating worse distress.
Change in symptoms and signs of constipation as assessed by score on the Patient Assessment of Constipation Symptoms (PAC-SYM) scale
时间窗: pre-transplant, post-treatment within weeks 11 to 12
The PAC-SYM is a 12-item questionnaire that assesses abdominal, rectal, and stool symptoms, with each item scored from 0 (No symptoms) to 4 (Very severe symptoms), for a total score range of 0-48, with a higher score indicating worse constipation severity.
Change in Gastrointestinal Symptom Severity as Assessed by the Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM)
时间窗: pre-transplant, post-treatment within weeks 11 to 12
Total score ranges from 0 (none or absent) to 5 (very severe), with a higher score indicating a worse outcome.
Change in gut transit times (assessed by Sitz markers and X-ray)
时间窗: pre-transplant, post-treatment within weeks 11 to 12
Number of participants who show an improvement in constipation and/or significant bloating symptoms as indicated by the stool diary
时间窗: from baseline to end of study (week 12)
次要结局
- Change in alpha diversity of the microbiome(pre-transplant, post-treatment within weeks 11 to 12)
- Change in beta diversity of the microbiome(pre-transplant, post-treatment within weeks 11 to 12)
研究者
Zsuzsanna Hortobagyi Mcmahan
Associate Professor of Medicine, Co-Director of the UTHealth Scleroderma Center
The University of Texas Health Science Center, Houston