Fecal Microbiota Transplantation for the Treatment of ICU Delirium

NCT07348471 | Not Yet Recruiting

• 1 other identifier: zjc202507
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

Delirium in the intensive care unit (ICU) is a prevalent and serious neurological complication among critically ill patients, with large multicenter studies reporting an incidence of 30% to 80%, particularly in those requiring mechanical ventilation. Delirium is not only associated with prolonged ICU and hospital stays but also with increased morbidity and mortality. Notably, up to 40% of survivors suffer from persistent cognitive dysfunction that may last for months or even years. Despite current standard pharmacological interventions-such as haloperidol and second-generation antipsychotics-failing to demonstrate significant clinical benefit in phase III trials, non-pharmacological strategies remain challenging to implement due to environmental and operational constraints within the ICU. This unmet clinical need underscores the imperative to develop novel, effective therapeutic approaches. Emerging evidence suggests that ICU-acquired gut microbiota dysbiosis plays a pivotal role in the pathogenesis of delirium. Dysbiosis can compromise intestinal barrier integrity, promoting systemic inflammation and increasing susceptibility to various forms of delirium, including acute illness-related and postoperative types. These effects are likely mediated through the "gut-microbiota-brain axis," which may represent a central mechanism underlying neurocognitive dysfunction in critical illness. Preclinical studies have demonstrated that fecal microbiota transplantation (FMT) can restore microbial balance and exert beneficial effects on neurological function. FMT has shown promise in ameliorating cognitive deficits in models of Alzheimer's disease, chronic cerebral hypoperfusion, traumatic brain injury, and chronic unpredictable mild stress (CUMS). Clinically, FMT has been associated with cognitive improvement in patients with dementia, recurrent Clostridioides difficile infection, and sepsis-associated encephalopathy. With expanding applications in both gastrointestinal and extraintestinal disorders, FMT has emerged as a transformative therapeutic modality, supported by robust short- and long-term safety and efficacy data. This study aims to evaluate whether FMT can alleviate delirium severity, correct gut microbiota dysbiosis at 0, 72, and 120 hours post-enrollment, attenuate intestinal barrier dysfunction, reduce systemic inflammation and disease severity, shorten ICU length of stay, and lower rates of ICU mortality, in-hospital mortality, and 28-day all-cause mortality-ultimately positioning FMT as a potential breakthrough intervention for ICU delirium.

Conditions

Delirium

Outcome Measures

Primary Outcomes (1)

• Delirium-free days (DFDs)

  The CAM-ICU is a standardized tool specifically designed for the rapid screening of delirium in ICU patients. It achieves efficient diagnosis by evaluating indicators including consciousness state, attention, and disordered thinking. and perceptual abnormalities. Delirium can be diagnosed if features 1 and 2 are met, and at least 3 or 4 are present. The assessment process is standardized, and medical staff can operate independently after training. For patients who survived and were discharged from the ICU or hospital during the study observation period, the entire period subsequent to their discharge date shall be counted as delirium-free. For patients who died during the study observation period, the interval from their date of death to the end of the observation period shall be recorded as 0 delirium-free days. DFDs = Total observation days - Days with delirium - Days with coma - Days from death to the end of observation.

  During the first 28 days post-enrollment

Secondary Outcomes (11)

• CAM-ICU-7 score

  From ICU admission to ICU discharge or death during ICU stay.

• Changes in intestinal microbiota composition

  At 0, 72, and 120 hours post-inclusion

• Alterations in serum metabolites

  At 0, 72, and 120 hours post-inclusion

• Acute Gastrointestinal Injury (AGI) Score

  At 0, 24, 48, 72, 96, and 120 hours post-inclusion

• APACHE ⅡScore

  At 0, 24, 48, 72, 96, and 120 hours post-inclusion

Study Arms (2)

Control group

NO INTERVENTION

The control group received standard ICU care, which includes monitoring vital signs, managing underlying conditions, infection treatment, nutritional support, and sedation or analgesia as per established clinical guidelines. These patients did not receive fecal microbiota transplantation (FMT). Treatment decisions were made by the attending physician according to standard ICU protocols and routine clinical practice.

FMT intervention Group

EXPERIMENTAL

FMT was administered via nasojejunal tube in addition to standard ICU care. A volume of 50-100 mL of intestinal microbiota suspension was delivered daily through the nasojejunal tube over a three-day period, between 11:00 and 13:00 each day.

Other: Intestinal microbiota suspension

Interventions

Intestinal microbiota suspension OTHER

FMT was administered via a nasojejunal tube daily for three consecutive days, between 11:00 and 13:00. Each 50-100 mL dose, derived from 100-150 g of adolescent donor feces diluted to 300 mL. Patients fasted for 2 hours before and after FMT, except for permitted water intake. Intravenous antibiotics were withheld unless active infection was confirmed. If pathogens were considered colonizing and the patient remained stable, systemic antibiotics were avoided. Localized treatments, such as nebulized antibiotics, were allowed as needed. All antibiotic use required clinical justification and individual assessment to minimize interference with FMT. Oral antibiotics were prohibited after FMT initiation to protect engraftment and microbial integrity.

FMT intervention Group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age ≥ 18 years old, no ethnic or gender restrictions;
• \. CAM-ICU-positive delirium;
• \. Signed written informed consent.

You may not qualify if:

• \. Routine administration of antipsychotic medications: Conventional antipsychotic therapy refers to the daily ingestion or application of any sustained-release formulation (in any dosage form) of antipsychotic drugs with the ATC code N05A (in any form), including the following agents:
• Typical antipsychotics: Chlorprothixene, Flupentixol, Haloperidol, Levomepromazine, Loxapine, Melperone, Perphenazine, Pericyazine, Pimozide, Prochlorperazine, Zuclopenthixol, Pimavanserin, Sulpiride.
• Atypical antipsychotics: Amisulpride, Aripiprazole, Asenapine, Clozapine, Lurasidone, Olanzapine, Paliperidone, Quetiapine, Risperidone, Sertindole, Ziprasidone. However, the non-habitual administration of antipsychotic medications in the general ward prior to the patient's ICU admission (e.g., for the management of delirium) is deemed acceptable. Nevertheless, antipsychotic therapy should be discontinued upon the patient's ICU admission.
• \. Severe systemic infection in the early stage of resuscitation, hemodynamic instability or insufficient tissue perfusion, and severe imbalance of water, electrolyte and acid-base.
• \. Patients with a high risk of death within 5 days as judged by the clinician, or those whose treatment decisions are restricted.
• \. Active major gastrointestinal bleeding, perforation, or other severe damage to the intestinal barrier.
• \. Patients who cannot tolerate 50% of their caloric requirements through enteral nutrition due to severe diarrhea, significant fibrotic intestinal stenosis, severe gastrointestinal bleeding, or high-flow enteric fistula.
• \. Planned or recent abdominal surgery (within 14 days).
• \. Currently diagnosed with fulminant colitis or toxic megacolon.
• \. Recently received high-risk immunosuppressive or cytotoxic drug treatment: such as rituximab, doxorubicin, or medium to high-dose corticosteroids (20 mg/d prednisone or higher) for more than 4 weeks.
• \. Pregnant or lactating women.
• \. Participated in other clinical trials as a subject within the past 3 months or at the time of enrollment.
• \. Delirium assessment non applicable: this includes language barriers (patients with foreign language where delirium assessment cannot be confidently performed by the site staff), patients who are deaf, blind or aphasic. Comatose patients are not applicable for delirium assessment. Coma is defined by the following levels of consciousness: RASS -4 to -5. Further, RASS -3 may be considered as coma if this is the judgement of the treating physician. If a patient's coma is considered related to administration of sedative agents, an effort should be made to reduce or terminate the sedative treatment, according to the clinician's discretion.
• \. Doubtful validity of informed consent: subjects with mental illness, intellectual disability, poor motivation, or other factors that limit the validity of informed consent for participation in this study.

Sponsors & Collaborators

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

MeSH Terms

Conditions

Delirium

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Jiancheng Zhang

Study Record Dates

• First Submitted: November 24, 2025
• First Posted: January 16, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: January 16, 2026

Record last verified: 2026-01