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

Overview

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.

Interventions

• 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.

Primary outcome measures

• Changes of weight and height [Time frame: baseline, 8 weeks post transplantation]
• Changes of the third lumbar vertebrae skeletal muscle mass and height [Time frame: baseline, 8 weeks post transplantation]
• Changes of weight [Time frame: baseline, 8 weeks post transplantation]

Secondary outcome measures (12)

• Changes of Patient-Generated Subjective Global Assessment (PG-SGA) [Time frame: baseline, 8 weeks post transplantation]
• Changes of the Gastrointestinal Symptom Rating Scale(GSRS) [Time frame: baseline, 4 weeks, 8 weeks post transplantation]
• 60-day readmission rate [Time frame: From enrollment to the end of treatment at 8 weeks]
• The incidence of treatment-related adverse events (AE) assessed by CTCAE, Version 5.0 [Time frame: From enrollment to the end of treatment at 8 weeks]
• Changes of the 5-level EuroQoL Group's 5-dimension (EQ-5D-5L) [Time frame: baseline, 4 weeks, 8 weeks post transplantation]
• Changes of the Pittsburgh Sleep Quality Index (PSQI) [Time frame: baseline, 4 weeks, 8 weeks post transplantation]
• Changes of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) [Time frame: baseline, 4 weeks, 8 weeks post transplantation]
• The difference of the gut microbiota composition before and after washed microbiota transplantation [Time frame: baseline, 8 weeks post transplantation]
• Change of insulin-like growth factor I(IGF-I) [Time frame: baseline, 8 weeks post transplantation]
• Changes of hemoglobin [Time frame: baseline, 8 weeks post transplantation]
• Changes of albumin [Time frame: baseline, 8 weeks post transplantation]
• Changes of prealbumin [Time frame: baseline, 8 weeks post transplantation]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The Second Affiliated Hospital of Nanjing Medical University — Nanjing

Publications

• 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. PMID 19212169
• 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. PMID 34523717
• 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. PMID 23160295
• 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. PMID 34746161
• 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 PMID 31170412
• 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. PMID 27556065

Identifiers

NCT: NCT05439135 · DELIV2022N002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗