FMT for Feeding Intolerance Due to Gastrointestinal Dysfunction in Critically Ill Patients (FMT-FIT)

Fecal Microbiota Transplantation for Feeding Intolerance Due to Gastrointestinal Dysfunction in Critically Ill Patients: A Single-Center, Single-Blind, Randomized Controlled Trial

Critically ill patients admitted to the intensive care unit (ICU) frequently present with gastrointestinal dysfunction and are at elevated risk of malnutrition. Gastrointestinal dysfunction is correlated with adverse clinical outcomes, including prolonged mechanical ventilation duration, extended ICU length of stay, and increased 90-day mortality.

In critically ill ICU patients, severe gut microbiota dysbiosis and intestinal barrier impairment may occur due to the burden of primary critical illnesses, as well as the administration of proton pump inhibitors and antibiotics. This cascade contributes to a high prevalence of gastrointestinal dysfunction, alongside profound gut-derived systemic inflammatory responses and organ damage. Given the pivotal role of gut microbiota in maintaining intestinal homeostasis, fecal microbiota transplantation (FMT) holds promise as a novel therapeutic strategy for enteral feeding intolerance secondary to gastrointestinal dysfunction in critically ill ICU patients.

This study intends to deliver FMT via a nasojejunal tube to critically ill patients with gastrointestinal dysfunction admitted to the ICU. Its objectives are to evaluate the intervention's effects on gastrointestinal function recovery and the alleviation of enteral feeding intolerance, while also assessing its impacts on intestinal barrier function, gut microbiota composition and metabolic profiles, serum metabolite signatures, immune-inflammatory responses (including lymphocyte subsets, cytokines, C-reactive protein, and procalcitonin), ICU delirium, ICU sleep quality, and clinical outcomes (encompassing ICU mortality, in-hospital mortality, 28-day all-cause mortality, 90-day all-cause mortality, 90-day readmission rate, and 90-day incidence of secondary infections).

Study Overview

• Status: Not yet recruiting
• Conditions: Gastrointestinal Dysfunction; Feeding Intolerance; Critically Ill Intensive Care Unit Patients
• Intervention / Treatment: Other: Fecal microbiota transplantation (FMT)

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jiancheng Zhang; Phone Number: +86-13554105815; Email: zhjcheng1@126.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 460022
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Jiancheng Zhang; Phone Number: +86-13554105815; Email: zhjcheng1@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 18 to 70 years inclusive, regardless of ethnicity or gender;
2. Female participants are either non-fertile (i.e., physiologically incapable of pregnancy, including women with ≥2 years of menopause) or have no pregnancy plans;
3. Have been admitted to the ICU for ≥24 hours;
4. Expected ICU stay ≥7 days after study enrollment;
5. Screened positive for ≥1 manifestation of gastrointestinal dysfunction (intra-abdominal hypertension [IAH], massive gastric retention, diarrhea, lower gastrointestinal paralysis, bowel dilatation); enteral nutrition is then implemented under the guidance of the enteral feeding intolerance (FI) score, and participants with persistent FI after a 3-day trial are formally enrolled;
6. Participants can actively cooperate or passively complete relevant examinations and follow-up procedures;
7. Have signed a written informed consent form.

Exclusion Criteria:

1. Severe systemic infection in the early resuscitation phase, with hemodynamic instability, insufficient tissue perfusion, or severe fluid-electrolyte and acid-base imbalances;
2. Patients assessed by clinicians as having a high risk of death within 5 days, or those with restricted treatment decisions;
3. Active gastrointestinal bleeding, perforation, or other conditions with severe intestinal barrier impairment;
4. Patients unable to tolerate enteral nutrition meeting 50% of caloric requirements due to severe diarrhea, significant fibrotic intestinal stenosis, massive gastrointestinal bleeding, or high-output enterocutaneous fistula;
5. Planned or recent abdominal surgery (within 14 days prior to enrollment);
6. Current diagnosis of fulminant colitis or toxic megacolon;
7. Neutropenia (neutrophil count < 1500 cells/µL);
8. Patients with congenital or acquired immunodeficiency disorders;
9. Recent receipt of high-risk immunosuppressive or cytotoxic agents, e.g., rituximab, doxorubicin, or medium-to-high-dose corticosteroids (≥ 20 mg/day prednisone equivalent) for a duration of > 4 weeks;
10. Pregnant or lactating women;
11. Participation in another clinical trial as a subject at the time of enrollment or within 3 months prior to enrollment;
12. Doubtful validity of informed consent: subjects with mental illness, intellectual disability, poor motivation, or other factors that restrict the validity of informed consent for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group; Patients received standard ICU care.
Experimental: FMT intervention group; Patients received FMT via a nasojejunal tube in addition to standard ICU care. Specifically, 50-100 mL of intestinal microbiota suspension was administered daily via the nasojejunal tube between 11:00 and 13:00 for three consecutive days.	Other: Fecal microbiota transplantation (FMT); Patients received FMT via a nasojejunal tube in addition to standard ICU care. Specifically, 50-100 mL of intestinal microbiota suspension was administered daily via the nasojejunal tube between 11:00 and 13:00 for three consecutive days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Enteral nutrition FI improvement rate	24, 48, 72, 96, and 120 hours after study enrollment

Secondary Outcome Measures

Outcome Measure	Time Frame
Gut microbiota composition as well as α and β diversity measured from rectal swabs by 16S rRNA gene sequencing	24-0 hours and 120 hours after study enrollment
Fecal metabolite profile (by untargeted LC-MS) from rectal swabs	24-0 hours and 120 hours after study enrollment
Serum metabolite profile (by untargeted LC-MS)	24-0 hours and 120 hours after study enrollment
Serum level of citrulline	0, 24, 48, 72, 96, and 120 hours after study enrollment
APACHE II score	0, 24, 48, 72, 96, and 120 hours after study enrollment
SOFA score	0, 24, 48, 72, 96, and 120 hours after study enrollment
Cumulative intravenous dose of vasopressor agents (including norepinephrine, epinephrine, dobutamine, etc.)	0, 24, 48, 72, 96, and 120 hours after study enrollment
Serum level of C-reactive protein	0, 24, 48, 72, 96, and 120 hours after study enrollment
Serum level of procalcitonin	0, 24, 48, 72, 96, and 120 hours after study enrollment
Peripheral blood level of cytokines (including IL-6, IL-17, TNF-α, IL-10, IL-1β, etc.)	0 and 120 hours after study enrollment
Peripheral blood lymphocyte subsets (including CD4+ T, CD8+ T, B lymphocytes, NK cells, etc.)	0, 24, 48, 72, 96, and 120 hours after study enrollment
ICU mortality	Within 28 days after study enrollment
In-hospital mortality	Within 60 days after study enrollment
28-day all-cause mortality	Within 28 days after study enrollment
90-day all-cause mortality	Within 90 days after study enrollment
90-day readmission rate	Within 90 days after study enrollment
90-day secondary infection rate	Within 90 days after study enrollment

Collaborators and Investigators

• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Publications and helpful links

General Publications

• Piton G, Manzon C, Cypriani B, Carbonnel F, Capellier G. Acute intestinal failure in critically ill patients: is plasma citrulline the right marker? Intensive Care Med. 2011 Jun;37(6):911-7. doi: 10.1007/s00134-011-2172-x. Epub 2011 Mar 12.
• Uhde M, Ajamian M, Caio G, De Giorgio R, Indart A, Green PH, Verna EC, Volta U, Alaedini A. Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Gut. 2016 Dec;65(12):1930-1937. doi: 10.1136/gutjnl-2016-311964. Epub 2016 Jul 25.
• Schluter J, Peled JU, Taylor BP, Markey KA, Smith M, Taur Y, Niehus R, Staffas A, Dai A, Fontana E, Amoretti LA, Wright RJ, Morjaria S, Fenelus M, Pessin MS, Chao NJ, Lew M, Bohannon L, Bush A, Sung AD, Hohl TM, Perales MA, van den Brink MRM, Xavier JB. The gut microbiota is associated with immune cell dynamics in humans. Nature. 2020 Dec;588(7837):303-307. doi: 10.1038/s41586-020-2971-8. Epub 2020 Nov 25.
• McClave SA, Patel J, Bhutiani N. Should fecal microbial transplantation be used in the ICU? Curr Opin Crit Care. 2018 Apr;24(2):105-111. doi: 10.1097/MCC.0000000000000489.
• Heming N, Carlier R, Prigent H, Mekki A, Jousset C, Lofaso F, Ambrosi X, Bounab R, Maxime V, Mansart A, Crenn P, Moine P, Foltzer F, Cuenoud B, Konz T, Corthesy J, Beaumont M, Hartweg M, Roessle C, Preiser JC, Breuille D, Annane D. Effect of an enteral amino acid blend on muscle and gut functionality in critically ill patients: a proof-of-concept randomized controlled trial. Crit Care. 2022 Nov 17;26(1):358. doi: 10.1186/s13054-022-04232-5.
• Yadegar A, Bar-Yoseph H, Monaghan TM, Pakpour S, Severino A, Kuijper EJ, Smits WK, Terveer EM, Neupane S, Nabavi-Rad A, Sadeghi J, Cammarota G, Ianiro G, Nap-Hill E, Leung D, Wong K, Kao D. Fecal microbiota transplantation: current challenges and future landscapes. Clin Microbiol Rev. 2024 Jun 13;37(2):e0006022. doi: 10.1128/cmr.00060-22. Epub 2024 May 8.
• Beyi AF, Wannemuehler M, Plummer PJ. Impacts of Gut Microbiota on the Immune System and Fecal Microbiota Transplantation as a Re-Emerging Therapy for Autoimmune Diseases. Antibiotics (Basel). 2022 Aug 12;11(8):1093. doi: 10.3390/antibiotics11081093.
• Arunachala Murthy T, Chapple LS, Lange K, Marathe CS, Horowitz M, Peake SL, Chapman MJ. Gastrointestinal dysfunction during enteral nutrition delivery in intensive care unit (ICU) patients: Risk factors, natural history, and clinical implications. A post-hoc analysis of The Augmented versus Routine approach to Giving Energy Trial (TARGET). Am J Clin Nutr. 2022 Aug 4;116(2):589-598. doi: 10.1093/ajcn/nqac113.
• Deane A, Chapman MJ, Fraser RJ, Bryant LK, Burgstad C, Nguyen NQ. Mechanisms underlying feed intolerance in the critically ill: implications for treatment. World J Gastroenterol. 2007 Aug 7;13(29):3909-17. doi: 10.3748/wjg.v13.i29.3909.
• Nguyen NQ, Fraser RJ, Chapman MJ, Bryant LK, Holloway RH, Vozzo R, Wishart J, Feinle-Bisset C, Horowitz M. Feed intolerance in critical illness is associated with increased basal and nutrient-stimulated plasma cholecystokinin concentrations. Crit Care Med. 2007 Jan;35(1):82-8. doi: 10.1097/01.CCM.0000250317.10791.6C.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: June 1, 2026
• First Submitted That Met QC Criteria: June 5, 2026
• First Posted (Actual): June 11, 2026

Study Record Updates

• Last Update Posted (Actual): June 11, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Therapeutics; Biological Therapy; Fecal Microbiota Transplantation
• Other Study ID Numbers: zjc202402

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No