Clinical trial NCT05439135: Washed Microbiota Transplantation for Malnutrition After Nonphysiological Reconstruction of the Upper Gastrointestinal Tract
Official title: An Open-label, Multicenter, Randomized Clinical Trial for Malnutrition After Nonphysiological Reconstruction of the Upper Gastrointestinal Tract: Washed Microbiota Transplantation Via Mid-gut Tube Versus Colonic Transendoscopic Enteral Tube
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Malnutrition
Gastroenterostomy
Keywords: washed microbiota transplantation
fecal microbiota transplant
malnutrition
enteral nutrition
cachexia
upper gastrointestinal rerouting surgery
delivery
nonphysiological reconstruction of the upper gastrointestinal tract
Lead sponsor: The Second Hospital of Nanjing Medical University
Sponsor class: OTHER
Collaborators: name: The First Affiliated Hospital of Guangdong Pharmaceutical University
name: Nanjing Medical University
name: Wuxi No. 2 People's Hospital
name: Jiangxi University of Chinese Medicine Affiliated Hospital
name: Hubei Hospital of Traditional Chinese Medicine
name: The Affiliated Hospital Of Southwest Medical University
name: Tang-Du Hospital
name: Huzhou Central Hospital
name: West China Forth University Hospitalï¼ŒSichuan University
name: The Affiliated People's hospital of Ningbo Univercity
name: Guangzhou First People Hospital of Guangzhou Medical University
name: The First Affiliated Hospital of Anhui University of Chinese Medicine
name: Beijing Rectum Hospital
name: Dazhou Central Hospital
name: The Second Affiliated Hospital of Dalian Medical University
name: Second Affiliated Hospital of Guangzhou Medical University
name: The 901th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army
name: YI'AN PEOPLE'S HOSPITAL
name: Hunan Aerospace Hospital
name: Jiamusi City Hospital of Traditional Chinese Medicine
name: The First People's Hospital of Kunshan
name: LanZhou University
name: Jingxing xian yiyuan
name: TAIHE country people's hospital
name: Tailai County People's Hospital
name: Armed Police Characteristic Medical Center
name: First Affiliated Hospital Xi'an Jiaotong University
First posted: 2022-06-30
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a prospective, randomized, multicenter study to evaluate WMT in improving nutritional status in malnourished patients who underwent nonphysiological reconstruction of the upper gastrointestinal tract. In this multicenter trial, sixty-two patients will be enrolled in forteen Chinese sites. Participants will be randomized at a ratio of 1:1 to receive three WMTs through either mid-gut tube or colonic TET. After WMT, each participant will receive free diet plus home enteral nutrition. Home enteral nutrition should last for 2 months at home, with blood, urine and stool samples taken and stored at baseline and 2 months after WMT.

Detailed description: Background: Malnutrition is a common complication of nonphysiological reconstruction of the upper gastrointestinal tract. The potential of washed microbiota transplantation (WMT) in improving nutritional status have been reported. The surgery procedure alters the anatomy and physiology of the digestive tract, which might impact the efficacy and safety of WMT when choosing different delivery way. This study aims to explore the optimal delivery of WMT in malnourished patients after rerouting of the upper gastrointestinal tract.

Methods and design: This multicenter, open-label, and randomized controlled trial will be conducted at forteen hospitals in China. Enteral nutrition (EN) will be administrated at enrollment. Participants will be then randomized at a ratio of 1:1 to receive three WMTs through either mid-gut tube or colonic transendoscopic enteral tubing (TET). Then the patients will receive free diet coupled with home enteral nutrition (HEN) for 8 weeks in both groups, with blood, urine and stool samples taken and stored at baseline and 2 months after WMT. The observation duration is 8 weeks. The primary endpoint is nutritional status of the patients. The nutritional status data obtained at baseline and 8 weeks after discharge includes body mass index (BMI) and skeletal muscle index (SMI). The secondary endpoints are nutritional assessment, nutrition-based laboratory indices, 60-day readmission rate, quality of life, gastrointestinal symptom scale, the safety of WMT and further analysis of the biological specimens.

Conclusion: It is estimated that WMT would help improve nutrition status. Moreover, this trial has the potential to identify the optimal delivery of WMT for patients undergoing nonphysiological reconstruction of the upper gastrointestinal tract.

Eligibility criteria: Inclusion Criteria:

* Patients undergone nonphysiological reconstruction of the gastrointestinal tract (such as Billroth-II, Roux-en-Y, Child, Whipple reconstruction)
* Aged over 18 years old;
* Malnutrition is assessed by Nutritional Risk Screening 2002 score≥3 and Patient Generated Subjective Global Assessment (PG-SGA) score≥4;
* Written informed consent;

Exclusion Criteria:

* Expected survival time \< 3 months;
* Still on anti-tumor therapy or it is expected during the visit;
* Complicated with ascites or edema caused by malnutrition;
* Known organic gastrointestinal disease (e.g., gastrointestinal infection, inflammatory bowel disease, or radiation enteritis);
* Undergone other gastrointestinal surgery (e.g., enterectomy, enterostomy, or gastrostomy) except appendectomy or anal fistula surgery;
* Complicated with contraindications of enteral nutrition such as ileus, active gastrointestinal bleeding, and shock;
* Cannot tolerate gastroscopy or colonoscopy;
* Severe comorbidities (e.g., diabetes, cardiopulmonary failure, severe liver or or kidney diseases);
* Complicated with other wasting diseases (e.g., active tuberculosis, hyperthyroidism, diabetes, HIV, active hepatitis, hip fracture, craniocerebral injury, etc.);
* A history of anti-infective treatment within 30 days before enrollment; or need anti-infective treatment at the time of enrollment; or unwilling to stop taking drugs that affect gut microbes, such as probiotics;
* Can not tolerate oral enteral nutrition;
* Women who are pregnant or breastfeeding;
* Participating in another clinical trial;
* Deemed unsuitable for inclusion by the investigators.

Primary outcomes:
measure: Changes of weight and height
timeFrame: baseline, 8 weeks post transplantation
measure: Changes of the third lumbar vertebrae skeletal muscle mass and height
timeFrame: baseline, 8 weeks post transplantation
Secondary outcomes:
measure: Changes of Patient-Generated Subjective Global Assessment (PG-SGA)
timeFrame: baseline, 8 weeks post transplantation
measure: Changes of the Gastrointestinal Symptom Rating Scale(GSRS)
timeFrame: baseline, 4 weeks, 8 weeks post transplantation
measure: 60-day readmission rate
timeFrame: From enrollment to the end of treatment at 8 weeks
measure: The incidence of treatment-related adverse events (AE) assessed by CTCAE, Version 5.0
timeFrame: From enrollment to the end of treatment at 8 weeks
measure: Changes of the 5-level EuroQoL Group's 5-dimension (EQ-5D-5L)
timeFrame: baseline, 4 weeks, 8 weeks post transplantation
measure: Changes of the Pittsburgh Sleep Quality Index (PSQI)
timeFrame: baseline, 4 weeks, 8 weeks post transplantation
measure: Changes of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)
timeFrame: baseline, 4 weeks, 8 weeks post transplantation
measure: The difference of the gut microbiota composition before and after washed microbiota transplantation
timeFrame: baseline, 8 weeks post transplantation
measure: Change of insulin-like growth factor I(IGF-I)
timeFrame: baseline, 8 weeks post transplantation
measure: Changes of hemoglobin
timeFrame: baseline, 8 weeks post transplantation
measure: Changes of albumin
timeFrame: baseline, 8 weeks post transplantation
measure: Changes of prealbumin
timeFrame: baseline, 8 weeks post transplantation
measure: Changes of cholesterol
timeFrame: baseline, 8 weeks post transplantation
measure: Changes of transferrin
timeFrame: baseline, 8 weeks post transplantation
measure: Changes of C-reactive protein
timeFrame: baseline, 8 weeks post transplantation
measure: Changes of full spectrum of bile acidsare
timeFrame: baseline, 8 weeks post transplantation
measure: Changes of glucose breath testing
timeFrame: baseline, 8 weeks post transplantation
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University
state: Jiangsu
Study officials:
References:
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citation: Levine A, Wine E, Assa A, Sigall Boneh R, Shaoul R, Kori M, Cohen S, Peleg S, Shamaly H, On A, Millman P, Abramas L, Ziv-Baran T, Grant S, Abitbol G, Dunn KA, Bielawski JP, Van Limbergen J. Crohn's Disease Exclusion Diet Plus Partial Enteral Nutrition Induces Sustained Remission in a Randomized Controlled Trial. Gastroenterology. 2019 Aug;157(2):440-450.e8. doi: 10.1053/j.gastro.2019.04.021. Epub 2019 Jun 4.
citation: Peng Z, Xiang J, He Z, Zhang T, Xu L, Cui B, Li P, Huang G, Ji G, Nie Y, Wu K, Fan D, Zhang F. Colonic transendoscopic enteral tubing: A novel way of transplanting fecal microbiota. Endosc Int Open. 2016 Jun;4(6):E610-3. doi: 10.1055/s-0042-105205. Epub 2016 Apr 28.