Acute Pancreatitis, Fecal Microbiota Transplantation, Intestinal Bacteria Flora Disturbance, Intestinal Dysfunction
Conditions
Keywords
Severe acute pancreatitis, Fecal Microbiota Transplantation, Intestinal barrier dysfunction, Intestinal flora
Brief summary
The intestinal microbiota plays a pivotal role in the maintenance of intestinal homeostasis and protecting the gut against pathogens by competing for nutrients, creating the intestinal biological barrier and modulating the host immune system.After the onset of acute pancreatitis,the intestinal hypoperfusion and the release of inflammatory mediators result in intestinal barrier dysfunction and intestinal bacteria dysbiosis.This leads to Bacterial and endotoxin translocation, which may cause infectious complications which are major causes of death in SAP patients.Recently,FMT was shown its efficacy in the treatment of gastrointestinal(GI) diseases and non-GI disorders associated with Intestinal flora disturbance by re-establishing the damaged Intestinal Bacteria homeostasis.However,the mechanism by which FMT results in cure of diseases has been poorly understood.This study aims to investigate the therapeutic potential of FMT for SAP patients with intestinal barrier dysfunction.
Detailed description
Investigators aims to restore the intestinal bacteria homeostasis through FMT by retention enema with fresh bacteria,thus stabilizing intestinal barrier dysfunction,minimizing bacterial translocation and preventing infectious complications.The investigators will further examine the effect of FMT on inflammatory markers，the predictors of Intestinal barrier injury and the incidence of infectious complications.
Interventions
PROCEDUREFecal Microbiota Transplantation
FMT via a nasoduodenal tube with fresh bacteria from healthy donor
DRUGnormal saline
Normal saline via a nasoduodenal tube.
Sponsors
The First Affiliated Hospital of Nanchang University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of acute pancreatitis from the First Affiliated Hospital of Nanchang University according to the Classification of acute pancreatitis-2012: revision of the Atlanta classification and definitions by international consensus 2. Onset of pancreatitis within \<=2 weeks 3. complicated with gastrointestinal failure. Gastrointestinal failure was defined if the patients were complicated with obvious abdominal distention, abdominal rumbling sound weakening or disappearance, no self-defecation as well as intra-abdominal hypertension.
Exclusion criteria
1. SAP complicated by Gastrointestinal bleeding or Intestinal fistula 2. Pregnancy and lactation women 3. Not signed the informed consent 4. Diabetes and autoimmune diseases 5. Multiple organ failure. Organ failure was defined as a score of 2 or more using the modified Marshall scoring system including respiratory failure, renal failure and circulatory.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Gastrointestinal Failure Score Equal 0 | one week after intervention | The recovery of gastrointestinal dysfunction was assessed by gastrointectinal failure score. Gastrointestinal failure score is a comprehensive score for assessing gastrointestinal function. Gastrointestinal dysfunction score gets o point meaning enteral nutrition\> 50% of the required amount and no intra-abdominal hypertension. GIF score range from 0 to 4, and higher scores mean a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Infectious Complications | 120 days | The incidence of any infectious complications，such as infected pancreatic necrosis, infected ascites, bacteraemia, pneumonia, urinary tract infection. |
| Number of Participants With Organ Failure | 120 days | The incidence of organ failure,such as respiratory failure, renal failure, circulatory failure. |
| Number of Participants With Interventions or Surgery | 120 days | number of patients who need extra interventions or surgery |
| Length of Intensive Care Time and Hospital Stay | 6 months | patients' Length of Intensive care time and hospital stay due to the disease |
| Mortality | 120 days | patients who die due to the diseases |
| Diamine Oxidase（DAO） | one week after intervention | Plasma Diamine oxidase（DAO）level as a predictor in the diagnosis of Intestinal mucosal barrier injury. The rate of decline in DAO was calculated by ((value before intervention - value one week after intervention)/ value before intervention)\*100) |
| D-lactate | one week after intervention | Plasma D-lactate level as a predictor in the diagnosis of Intestinal mucosal. The rate of decline in D-lactate was calculated by ((value before intervention - value one week after intervention)/ value before intervention)\*100). |
Countries
China
Participant flow
Recruitment details
Participants were recruited between November 2017 and April 2019 from the intensive unit care, Department of Gastroenterology, First Affiliated Hospital of Nanchang University.
Participants by arm
| Arm | Count |
|---|---|
| FMT Group In the FMT group, participants received 200 mL fresh donor feces for twice (once every two days) via a nasoduodenal tube. | 30 |
| Control Group In the control group, participants received 200 mL normal saline for twice (once every two days) via a nasoduodenal tube. | 30 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | FMT Group | Total | Control Group |
|---|---|---|---|
| Age, Continuous | 47.2 years STANDARD_DEVIATION 12.4 | 48.6 years STANDARD_DEVIATION 13 | 49.9 years STANDARD_DEVIATION 13.7 |
| BMI | 26.3 kg/m^2 STANDARD_DEVIATION 3.7 | 26.0 kg/m^2 STANDARD_DEVIATION 3.9 | 25.6 kg/m^2 STANDARD_DEVIATION 4.2 |
| Causes of pancreatitis Alcohol | 6 Participants | 9 Participants | 3 Participants |
| Causes of pancreatitis Biliary | 9 Participants | 22 Participants | 13 Participants |
| Causes of pancreatitis Hypertriglyceridemia | 14 Participants | 25 Participants | 11 Participants |
| Causes of pancreatitis Other | 1 Participants | 4 Participants | 3 Participants |
| Drinker | 12 Participants | 20 Participants | 8 Participants |
| Iintra-abdominal pressure | 13.7 mmHg STANDARD_DEVIATION 2.4 | 14.1 mmHg STANDARD_DEVIATION 2.5 | 14.5 mmHg STANDARD_DEVIATION 2.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 30 Participants | 60 Participants | 30 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 30 participants | 60 participants | 30 participants |
| Sex: Female, Male Female | 7 Participants | 19 Participants | 12 Participants |
| Sex: Female, Male Male | 23 Participants | 41 Participants | 18 Participants |
| Smoker | 10 Participants | 19 Participants | 9 Participants |
| Time from admission to intervention | 2 days | 2 days | 1.5 days |
| Time from first symptoms to admission | 3 days | 3 days | 3 days |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 30 | 4 / 30 |
| other Total, other adverse events | 25 / 30 | 25 / 30 |
| serious Total, serious adverse events | 24 / 30 | 24 / 30 |
Outcome results
Primary
Number of Participants With Gastrointestinal Failure Score Equal 0
The recovery of gastrointestinal dysfunction was assessed by gastrointectinal failure score. Gastrointestinal failure score is a comprehensive score for assessing gastrointestinal function. Gastrointestinal dysfunction score gets o point meaning enteral nutrition\> 50% of the required amount and no intra-abdominal hypertension. GIF score range from 0 to 4, and higher scores mean a worse outcome.
Time frame: one week after intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FMT Group | Number of Participants With Gastrointestinal Failure Score Equal 0 | 12 Participants |
| Control Group | Number of Participants With Gastrointestinal Failure Score Equal 0 | 14 Participants |
Secondary
Diamine Oxidase（DAO）
Plasma Diamine oxidase（DAO）level as a predictor in the diagnosis of Intestinal mucosal barrier injury. The rate of decline in DAO was calculated by ((value before intervention - value one week after intervention)/ value before intervention)\*100)
Time frame: one week after intervention
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FMT Group | Diamine Oxidase（DAO） | -0.21 percent change of DAO |
| Control Group | Diamine Oxidase（DAO） | -0.05 percent change of DAO |
Secondary
D-lactate
Plasma D-lactate level as a predictor in the diagnosis of Intestinal mucosal. The rate of decline in D-lactate was calculated by ((value before intervention - value one week after intervention)/ value before intervention)\*100).
Time frame: one week after intervention
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FMT Group | D-lactate | 0.37 percent change of D-lactate |
| Control Group | D-lactate | -0.28 percent change of D-lactate |
Secondary
Length of Intensive Care Time and Hospital Stay
patients' Length of Intensive care time and hospital stay due to the disease
Time frame: 6 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| FMT Group | Length of Intensive Care Time and Hospital Stay | Intensive care stay | 9 days |
| FMT Group | Length of Intensive Care Time and Hospital Stay | Hospital stay | 18.5 days |
| Control Group | Length of Intensive Care Time and Hospital Stay | Intensive care stay | 11 days |
| Control Group | Length of Intensive Care Time and Hospital Stay | Hospital stay | 23 days |
Secondary
Mortality
patients who die due to the diseases
Time frame: 120 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FMT Group | Mortality | 3 Participants |
| Control Group | Mortality | 4 Participants |
Secondary
Number of Participants With Infectious Complications
The incidence of any infectious complications，such as infected pancreatic necrosis, infected ascites, bacteraemia, pneumonia, urinary tract infection.
Time frame: 120 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FMT Group | Number of Participants With Infectious Complications | Suspected or documented IPN | 10 Participants |
| FMT Group | Number of Participants With Infectious Complications | bacteremia | 9 Participants |
| FMT Group | Number of Participants With Infectious Complications | Documented IPN | 4 Participants |
| FMT Group | Number of Participants With Infectious Complications | pneumonia | 6 Participants |
| FMT Group | Number of Participants With Infectious Complications | infected ascites | 2 Participants |
| FMT Group | Number of Participants With Infectious Complications | Urinary tract infection | 3 Participants |
| FMT Group | Number of Participants With Infectious Complications | Any infectious complications | 15 Participants |
| Control Group | Number of Participants With Infectious Complications | Urinary tract infection | 7 Participants |
| Control Group | Number of Participants With Infectious Complications | Any infectious complications | 16 Participants |
| Control Group | Number of Participants With Infectious Complications | Documented IPN | 8 Participants |
| Control Group | Number of Participants With Infectious Complications | Suspected or documented IPN | 9 Participants |
| Control Group | Number of Participants With Infectious Complications | infected ascites | 2 Participants |
| Control Group | Number of Participants With Infectious Complications | bacteremia | 10 Participants |
| Control Group | Number of Participants With Infectious Complications | pneumonia | 8 Participants |
Secondary
Number of Participants With Interventions or Surgery
number of patients who need extra interventions or surgery
Time frame: 120 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FMT Group | Number of Participants With Interventions or Surgery | Percutaneous or endoscopic transmural necrosectomy | 6 Participants |
| FMT Group | Number of Participants With Interventions or Surgery | Mechanical ventilation | 12 Participants |
| FMT Group | Number of Participants With Interventions or Surgery | Open surgery | 1 Participants |
| FMT Group | Number of Participants With Interventions or Surgery | Renal replacement therapy | 2 Participants |
| FMT Group | Number of Participants With Interventions or Surgery | Percutaneous or endoscopic transmural drainage | 10 Participants |
| Control Group | Number of Participants With Interventions or Surgery | Renal replacement therapy | 3 Participants |
| Control Group | Number of Participants With Interventions or Surgery | Percutaneous or endoscopic transmural drainage | 11 Participants |
| Control Group | Number of Participants With Interventions or Surgery | Percutaneous or endoscopic transmural necrosectomy | 7 Participants |
| Control Group | Number of Participants With Interventions or Surgery | Open surgery | 1 Participants |
| Control Group | Number of Participants With Interventions or Surgery | Mechanical ventilation | 10 Participants |
Secondary
Number of Participants With Organ Failure
The incidence of organ failure,such as respiratory failure, renal failure, circulatory failure.
Time frame: 120 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FMT Group | Number of Participants With Organ Failure | Any persistent organ failure | 24 Participants |
| FMT Group | Number of Participants With Organ Failure | Persistent respiratory failure | 24 Participants |
| FMT Group | Number of Participants With Organ Failure | Persistent renal failure | 3 Participants |
| FMT Group | Number of Participants With Organ Failure | Persistent circulatory failure | 9 Participants |
| Control Group | Number of Participants With Organ Failure | Persistent circulatory failure | 11 Participants |
| Control Group | Number of Participants With Organ Failure | Any persistent organ failure | 23 Participants |
| Control Group | Number of Participants With Organ Failure | Persistent renal failure | 5 Participants |
| Control Group | Number of Participants With Organ Failure | Persistent respiratory failure | 21 Participants |