Washed Microbiota Transplantation for Malnutrition After Nonphysiological Reconstruction of the Upper Gastrointestinal Tract

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

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.

Study Overview

• Status: Recruiting
• Conditions: Malnutrition; Gastroenterostomy
• Intervention / Treatment: Other: washed microbiota transplantation

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.

• Study Type: Interventional
• Enrollment (Estimated): 62
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Recruiting
      • The Second Affiliated Hospital of Nanjing Medical University
      • Contact: Faming Zhang; Phone Number: +86-25-56662093; Email: fzhang@njmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: midgut; A soft TET tube is inserted into the colon via the paraffin-lubricated gastroscope channel. If patients cannot tolerate endoscopy or anesthesia, or it is difficult to confirm the bypass intestine under endoscopy, a nasojejunal tube will be inserted under digital fluoroscopy.	Other: washed microbiota transplantation; Each patient will receive washed microbiota transplantation each day for three consecutive days. After WMT, participants will receive free diet plus home enteral nutrition (solution at a 750ml daily dosage that provides 750 kcal energy) at home for 8 weeks.; Other Names: home enteral nutrition
Experimental: colonic; A soft TET tube is inserted into the colon via the paraffin-lubricated colonoscope channel.	Other: washed microbiota transplantation; Each patient will receive washed microbiota transplantation each day for three consecutive days. After WMT, participants will receive free diet plus home enteral nutrition (solution at a 750ml daily dosage that provides 750 kcal energy) at home for 8 weeks.; Other Names: home enteral nutrition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of weight and height	Weight and height will be combined to report BMI in kg/m^2.	baseline, 8 weeks post transplantation
Changes of the third lumbar vertebrae skeletal muscle mass and height	The third lumbar vertebrae skeletal muscle mass represents the sum of the cross-sectional areas of the skeletal muscles at the L3 level, including the psoas major, the erector spinae, the quadratus lumborum, the musculus transversus abdominis, the obliquus externus abdominis and the obliquus internus abdominis. Skeletal muscle mass and height will be combined to report the third lumbar vertebrae skeletal muscle mass index(L3 SMI) in cm^2/m^2.	baseline, 8 weeks post transplantation
Changes of weight		baseline, 8 weeks post transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of Patient-Generated Subjective Global Assessment (PG-SGA)	Patient-Generated Subjective Global Assessment (PG-SGA) includes patient-generated historical components (Weight History, Food Intake, Symptoms and Activities and Function) and the professional part (Diagnosis, Age, Metabolic stress, and Physical Exam).	baseline, 8 weeks post transplantation
Changes of the Gastrointestinal Symptom Rating Scale(GSRS)	GSRS is a 13-item test to make a comprehensive assessment of common gastrointestinal symptom and each item receives a value from 0 to 3, with higher value indicating worse gastrointestinal condition.	baseline, 4 weeks, 8 weeks post transplantation
60-day readmission rate	The 60-day readmission is recorded and defined as nonelective readmission within 60 days after the treatment.	From enrollment to the end of treatment at 8 weeks
The incidence of treatment-related adverse events (AE) assessed by CTCAE, Version 5.0	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.).	From enrollment to the end of treatment at 8 weeks
Changes of the 5-level EuroQoL Group's 5-dimension (EQ-5D-5L)	EQ-5D-5L is a 5-dimension questionnaire measuring health state and each dimension represents the level from 1 to 5, with higher level indicating worse health state.	baseline, 4 weeks, 8 weeks post transplantation
Changes of the Pittsburgh Sleep Quality Index (PSQI)	PSQI is a self-rated questionnaire which assesses sleep quality over a 1-month time interval. Nineteen items generate seven component scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for seven components yields one global score, with higher score indicating worse sleep quality.	baseline, 4 weeks, 8 weeks post transplantation
Changes of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)	FACIT-Fatigue is a 13-item test measuring fatigue and each item receives a value from 0 to 4, with higher value indicating worse fatigue state.	baseline, 4 weeks, 8 weeks post transplantation
The difference of the gut microbiota composition before and after washed microbiota transplantation	The composition of the gut microbiota is evaluated by sequencing faecal metagenome. We evaluate the differences in the structure of the flora and its metabolism.	baseline, 8 weeks post transplantation
Change of insulin-like growth factor I(IGF-I)	Blood is tested for Insulin-like growth factor I.	baseline, 8 weeks post transplantation
Changes of hemoglobin	Blood is tested for hemoglobin	baseline, 8 weeks post transplantation
Changes of albumin	Blood is tested for albumin	baseline, 8 weeks post transplantation
Changes of prealbumin	Blood is tested for prealbumin	baseline, 8 weeks post transplantation
Changes of cholesterol	Blood is tested for cholesterol	baseline, 8 weeks post transplantation
Changes of transferrin	Blood is tested for transferrin	baseline, 8 weeks post transplantation
Changes of C-reactive protein	Blood is tested for C-reactive protein	baseline, 8 weeks post transplantation
Changes of full spectrum of bile acidsare	Blood is tested for full spectrum of bile acidsare, including Cholic acid, deoxycholic acid, chenodeoxycholic acid, urs/hyodeoxycholic acid, lithocholic acid, glycocholic acid, glycolithocholic acid, glycodeoxycholic acid, glycochenodeoxycholic acid, glycouran Deoxycholic acid, taurocholic acid, taurolithocholic acid, taurodeoxycholic acid, taurochenodeoxycholic acid, tauroursodeoxycholic acid.	baseline, 8 weeks post transplantation
Changes of glucose breath testing	A baseline breath sample was obtained, patients drank 50g glucose dissolved in 8 ounces of water, and breath samples were obtained at 15-minute intervals for 2 hours. Samples were analyzed to calculate breath H2 and/or breath CH4.	baseline, 8 weeks post transplantation

Collaborators and Investigators

• Sponsor: The Second Hospital of Nanjing Medical University
• Collaborators: LanZhou University; First Affiliated Hospital Xi'an Jiaotong University; Tang-Du Hospital; Nanjing Medical University; Second Affiliated Hospital of Guangzhou Medical University; Hubei Hospital of Traditional Chinese Medicine; The Affiliated Hospital Of Southwest Medical University; The Second Affiliated Hospital of Dalian Medical University; The First Affiliated Hospital of Guangdong Pharmaceutical University; Hunan Aerospace Hospital; Dazhou Central Hospital; The First People's Hospital of Kunshan; Jiangxi University of Chinese Medicine Affiliated Hospital; Wuxi No. 2 People's Hospital; The First Affiliated Hospital of Anhui University of Chinese Medicine; The Affiliated People's hospital of Ningbo Univercity; West China Forth University Hospital，Sichuan University; Guangzhou First People Hospital of Guangzhou Medical University; Huzhou Central Hospital; Beijing Rectum Hospital; The 901th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army; YI'AN PEOPLE'S HOSPITAL; Jiamusi City Hospital of Traditional Chinese Medicine; Jingxing xian yiyuan; TAIHE country people's hospital; Tailai County People's Hospital; Armed Police Characteristic Medical Center

Publications and helpful links

General Publications

• 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.
• 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.
• Csendes A, Burgos AM, Smok G, Burdiles P, Braghetto I, Diaz JC. Latest results (12-21 years) of a prospective randomized study comparing Billroth II and Roux-en-Y anastomosis after a partial gastrectomy plus vagotomy in patients with duodenal ulcers. Ann Surg. 2009 Feb;249(2):189-94. doi: 10.1097/SLA.0b013e3181921aa1.
• Nishizaki D, Ganeko R, Hoshino N, Hida K, Obama K, Furukawa TA, Sakai Y, Watanabe N. Roux-en-Y versus Billroth-I reconstruction after distal gastrectomy for gastric cancer. Cochrane Database Syst Rev. 2021 Sep 15;9(9):CD012998. doi: 10.1002/14651858.CD012998.pub2.
• Zhang F, Luo W, Shi Y, Fan Z, Ji G. Should we standardize the 1,700-year-old fecal microbiota transplantation? Am J Gastroenterol. 2012 Nov;107(11):1755; author reply p.1755-6. doi: 10.1038/ajg.2012.251. No abstract available.
• Xiang L, Yu Y, Ding X, Zhang H, Wen Q, Cui B, Zhang F. Exclusive Enteral Nutrition Plus Immediate vs. Delayed Washed Microbiota Transplantation in Crohn's Disease With Malnutrition: A Randomized Pilot Study. Front Med (Lausanne). 2021 Oct 22;8:666062. doi: 10.3389/fmed.2021.666062. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2024
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): October 31, 2025

Study Registration Dates

• First Submitted: June 19, 2022
• First Submitted That Met QC Criteria: June 26, 2022
• First Posted (Actual): June 30, 2022

Study Record Updates

• Last Update Posted (Actual): July 10, 2025
• Last Update Submitted That Met QC Criteria: July 6, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: delivery; malnutrition; cachexia; enteral nutrition; fecal microbiota transplant; washed microbiota transplantation; upper gastrointestinal rerouting surgery; nonphysiological reconstruction of the upper gastrointestinal tract
• Additional Relevant MeSH Terms: Nutrition Disorders; Malnutrition
• Other Study ID Numbers: DELIV2022N002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No