Washed Microbiota Transplantation for Chronic Constipation in Adults: a Single-center, Randomized, Double-blind, Placebo-controlled, Dose-exploring Clinical Study
Overview
- Phase
- Phase 1
- Intervention
- High-dose washed microbiota suspension
- Conditions
- Constipation
- Sponsor
- The Second Hospital of Nanjing Medical University
- Enrollment
- 18
- Locations
- 2
- Primary Endpoint
- The incidence of treatment-related adverse events (AE) assessed by CTCAE, Version 5.0
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a single-center, randomized, double-blind, placebo-controlled, dose-exploring clinical study to explore the safety and efficacy of washed microbiota transplantation (WMT) for patients with chronic constipation.
Detailed Description
At least 18 subjects who meet all the inclusion criteria but do not meet any exclusion criteria will be enrolled in this study. They will be randomly assigned to the high-dose group (high dose of washed microbiota suspension), the low-dose group (low dose of washed microbiota suspension) and the control group (placebo). Data of demographic characteristics, intestinal symptoms，medicine treatment usage and clinical outcomes will be collected. After treatment (D1-D4), they will enter the double-blind visit (D5, D18) for safety and efficacy evaluation. Open follow-up periods will be performed on days 32 and 60 after administration.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Meet all of the following inclusion criteria :
- •Voluntary sign informed consent, age 18-70 years old (including the threshold), male and female.
- •For subjects diagnosed with chronic constipation, the duration of the disease is at least 6 months, and the following conditions are met:
- •Frequency of spontaneous defecation \<3 times/week (spontaneous defecation refers to spontaneous defecation without the aid of remedial purgatives or manual assistance).
- •Dry and hard stool: More than a quarter of the stool is type 1 or 2 on the Bristol Fecal Trait Scale.
- •The subject or his/her legal representative has given informed consent, is fully aware of the purpose of the study, is able to communicate well with the investigator, and is able to understand and comply with the requirements of the study.
Exclusion Criteria
- •All exclusion criteria below are not met:
- •Outlet obstruction constipation, such as rectal mucosal prolapse.
- •History of abdominal and pelvic surgery, except for no intestinal complications after cholecystectomy, caesarean section, appendectomy, and treatment of intestinal polyps.
- •Combined with the colonoscopy results in the past 24 months, patients with intestinal stenosis caused by organic lesions of the digestive tract (such as tumor, inflammation, anal fissure, Crohn's disease, intestinal adhesion, ulcerative colitis, intestinal tuberculosis, etc.) and constipation.
- •Other systemic diseases involving the digestive tract (such as neurological diseases (such as Parkinson's disease, spinal cord injury, multiple sclerosis, etc.), muscle diseases (such as amyloidosis, dermatomyositis, etc.), mental disorders (such as depression, etc.), metabolic endocrine disorders (such as diabetes, hypothyroidism, etc.), or constipation caused by opioids.
- •Have a history of major surgery or severe trauma within 3 months and have not fully recovered.
- •There are contraindications for endoscopic intestinal catheterization via colonic approach, such as severe intestinal stenosis, obstruction, deep ulcer, and high risk of perforation. There are serious ulcers or a large number of false polyps in the fixation area, which is not suitable for fixation. The subject's behavior is seriously out of control.
- •Cardiac function and cardiac performance have any of the following abnormalities:
- •According to the New York Heart Association (NYHA) heart function rating, the heart function rating is grade III and above.
- •Subjects with new myocardial infarction or unstable angina pectoris within 6 months.
Arms & Interventions
High-dose group
The participant will receive a high dose of the washed microbiota suspension, with a bacterial quantity that is 10 times higher than the conventional clinical treatment dose, once daily for a duration of 4 days.
Intervention: High-dose washed microbiota suspension
Low-dose group
The participant will receive a low-dose washed microbiota suspension, with a bacterial quantity equivalent to the conventional clinical treatment dose. The washed microbiota suspension will be administered once on the first day, followed by placebo of equal volume for the next 3 days.
Intervention: Low-dose washed microbiota suspension
Control group
The patient will receive a placebo of equal volume once daily for a duration of 4 days.
Intervention: Placebo
Outcomes
Primary Outcomes
The incidence of treatment-related adverse events (AE) assessed by CTCAE, Version 5.0
Time Frame: Two-week post-WMT
The severity of AE was graded as mild (grade 1), moderate (grade 2), severe/disabling (grade 3), life threatening (grade 4), and death (grade 5). All AE were divided in definitely, probably and possibly related to treatment. The treatment-related AE we focused on included microbiota-related AEs (e.g., infection, diarrhea, abdominal pain, etc.) and route of delivery related AEs (e.g., nausea, vomiting, etc.).
Secondary Outcomes
- The incidence of treatment-related adverse events (AE) assessed by CTCAE, Version 5.0(Day 5，Four-week post-WMT，Eight-week post-WMT)
- The clinical response rate after treatment(One-week post-WMT，two-week post-WMT，Four-week post-WMT，Eight-week post-WMT)
- The weekly usage rate of assisted defecation drugs.(One-week post-WMT，Two-week post-WMT, Four-week post-WMT，Eight-week post-WMT)