Refractory Enteral Feeding IntoleranceNCT07864844
Gut Microbiota Structure, Functional and Metabolic Profiles, and Composite Biomarkers in ICU Adults With Refractory Enteral Feeding Intolerance
An observational study of Refractory Enteral Feeding Intolerance and Gut Microbiota, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.
Trial summary
Some adults in the intensive care unit (ICU) cannot receive enough nutrition through a feeding tube because of persistent digestive problems, even after standard measures to improve feeding. This condition is called refractory enteral feeding intolerance. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Enteral Feeding Intolerance, Gut Microbiota, Metabolic Profiles
- What is being tested?
- Naturally Occurring Exposures
- How many people
- 180 participants
- Where
- 1 siteChina
- Study dates
- 15 Oct 2026to 30 Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adults aged 18 years or older receiving care in the ICU at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, who have refractory enteral feeding intolerance (rEFI). Eligible patients remain unable to achieve an enteral energy intake of 20 kcal/kg/day despite 72 consecutive hours of feeding strategy adjustments and standard measures, including prokinetic medications. Patients will be enrolled consecutively if they meet all eligibility criteria, can provide a spontaneously passed stool sample or safely undergo rectal swab collection within the baseline sampling window, and provide written informed consent personally or through a legally authorized representative.
Who may be able to join
- Age ≥18 years.
- Receiving care in the ICU at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology.
- Meeting the protocol-defined criteria for refractory enteral feeding intolerance (rEFI): inability to achieve an enteral energy intake of 20 kcal/kg/day despite 72 consecutive hours of feeding strategy adjustments and standard measures, including prokinetic medications.
- A spontaneously passed stool sample can be obtained, or a rectal swab can be safely collected, within the permitted baseline sampling window.
- Written informed consent provided by the participant or their legally authorized representative. Participants who regain decision-making capacity will be informed again and asked to consent to continued participation.
Who cannot join
- Pregnancy or reasonable grounds for the investigator to suspect pregnancy. Active inflammatory bowel disease, major gastrointestinal surgery, or any other condition within the past 3 months that significantly alters intestinal anatomy and affects interpretation of the study findings.
- Receipt of fecal microbiota transplantation before ICU admission.
- Active gastrointestinal bleeding, severe coagulopathy, anorectal surgery or lesions, or other conditions that make rectal swab collection unsafe, together with an inability to obtain a spontaneously passed stool sample within the specified sampling window.
- Expected death within 24 hours, with informed consent and baseline procedures unable to be completed without interfering with emergency care.
- Refusal to participate by the participant or their legally authorized representative, or determination by the investigator that enrollment is inappropriate because of concerns regarding safety, adherence to study procedures, or data validity.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430022
Jiancheng Zhang, 13554105815, zhjcheng1@126.com
Jiancheng Zhang, zhjcheng1@126.com
About this study
Official title: Gut Microbiota Structure, Functional and Metabolic Profiles, and Composite Biomarkers in ICU Adults With Refractory Enteral Feeding Intolerance: A Prospective Observational Longitudinal Cohort Study
Some adults in the intensive care unit (ICU) cannot receive enough nutrition through a feeding tube because of persistent digestive problems, even after standard measures to improve feeding. This condition is called refractory enteral feeding intolerance. The community of microorganisms living in the gut, known as the gut microbiota, and the substances produced by these microorganisms and the body may be associated with feeding tolerance and recovery.
This prospective observational study will enroll approximately 180 adults with refractory enteral feeding intolerance at a single hospital. It aims to describe changes in their gut microbiota and metabolic profiles over time and identify combinations of microbial markers associated with improved feeding tolerance and adequate nutritional intake.
Read more
Stool samples or rectal swabs will be collected at enrollment, on days 3-5 and day 7, and, when feasible, near the end of the ICU stay. The samples will be used to examine the types of microorganisms present. Selected samples will also be analyzed for metabolic substances. Clinical information about nutrition, digestive symptoms, medications, illness severity, and treatments will be collected. Participants will be followed for up to 90 days to assess survival and unplanned hospital readmissions.
The study will examine whether microbial and metabolic patterns provide additional information about feeding improvement by day 7 beyond routine clinical assessments. Where suitable public datasets are available, findings will also be evaluated in other patient groups.
Participants will continue to receive usual medical care. The study does not assign treatments or change feeding decisions. Its findings may help guide future research on feeding intolerance, but participants are not expected to receive a direct medical benefit from taking part.
- Being tested
- Naturally Occurring Exposures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Naturally Occurring ExposuresOther
Serial stool samples or rectal swabs will be collected at enrollment, on days 3-5 and day 7, and, when feasible, before ICU discharge or death. Gut microbiota composition will be assessed using 16S rRNA gene sequencing. A prespecified subset of samples will undergo untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomic analysis. These assessments are performed for research purposes and will not guide treatment or feeding decisions. All participants will receive usual clinical care.
| Study group | Role | What they receive |
|---|---|---|
| ICU Adults With Refractory Enteral Feeding Intolerance | Not described Receives: Other: Naturally Occurring Exposures |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the ROC Curve of a Locked Baseline Microbial Biomarker Comprising at Least 15 Taxonomic Units for Feeding Intolerance Improvement by Day 7
The area under the receiver operating characteristic curve (AUC) will measure the ability of a locked composite microbial biomarker comprising at least 15 taxonomic units to distinguish participants with and without enteral feeding intolerance (EFI) improvement by day 7. The biomarker will be developed from baseline 16S rRNA gene sequencing data using participant-level nested cross-validation. All preprocessing, feature selection, and model tuning will occur within training folds. EFI improvement is defined as achieving an enteral energy intake of at least 20 kcal/kg/day with no reduction or discontinuation of feeding due to gastrointestinal intolerance for 24 consecutive hours. An AUC of 0.5 indicates chance-level discrimination, and an AUC of 1.0 indicates perfect discrimination.
Measured: Baseline (within 48 hours of T0) and day 7
Secondary outcomes (10)
Change in Gut Microbiota α Diversity Index From Baseline to Day 7
Within-participant change in the α diversity index, calculated as the day 7 value minus the baseline value using 16S rRNA gene sequencing data.
Measured: Baseline (within 48 hours of T0) and day 7
Bray-Curtis Dissimilarity Between Baseline and Day 7 Gut Microbiota Samples
Within-participant Bray-Curtis dissimilarity between baseline and day 7 microbial relative abundance profiles obtained by 16S rRNA gene sequencing. Values range from 0 to 1, with 0 indicating identical composition and higher values indicating greater differences in composition.
Measured: Baseline (within 48 hours of T0) and day 7.
Number of Fecal Metabolite Features With Significant Changes From Baseline to Day 7
Number of quality-controlled metabolite features showing significant changes in normalized signal intensity between paired baseline and day 7 samples in the prespecified nested metabolomics subgroup. Features will be measured using untargeted liquid chromatography-mass spectrometry. Statistical significance will be defined as a false discovery rate-adjusted q-value below 0.05.
Measured: Baseline (within 48 hours of T0) and day 7
Number of Predicted Microbial Functional Pathways With Significant Changes From Baseline to Day 7
Number of microbial functional pathways showing significant changes in predicted relative abundance between paired baseline and day 7 samples. Pathways will be inferred from 16S rRNA gene sequencing data using PICRUSt2. Statistical significance will be defined as a false discovery rate-adjusted q-value below 0.05. These measurements represent predicted functional potential rather than directly measured microbial activity.
Measured: Baseline (within 48 hours of T0) and day 7
Change in Cross-Validated AUC After Adding the Baseline Microbial Biomarker to a Clinical Model for Day 7 Feeding Intolerance Improvement
Difference in cross-validated AUC between a prespecified clinical model with the baseline microbial biomarker added and the same model without the biomarker, for EFI improvement by day 7. The difference will be calculated as the combined-model AUC minus the clinical-model AUC using identical participant-level validation folds. Positive values indicate additional discrimination provided by the biomarker.
Measured: Baseline (within 48 hours of T0) and day 7
Change in Cross-Validated AUC After Adding the Baseline Microbial Biomarker to a Clinical Model for Enteral Energy Target Achievement by Day 7
Difference in cross-validated AUC between a prespecified clinical model with the baseline microbial biomarker added and the same model without the biomarker, for achievement of an actual enteral energy intake of at least 20 kcal/kg/day by day 7. Parenteral energy intake is excluded. The difference will be calculated as the combined-model AUC minus the clinical-model AUC using identical participant-level validation folds.
Measured: Within 7 days after enrollment
Adjusted Odds Ratio for 28-Day All-Cause Mortality per Standard Deviation Increase in the Baseline Microbial Biomarker Score
Adjusted odds ratio for death from any cause by day 28 per one standard deviation increase in the baseline microbial biomarker score. Logistic regression will adjust for prespecified clinical covariates. Results will be reported with 95% confidence intervals. Mortality will be established using hospital records and telephone follow-up when necessary.
Measured: Within 28 days after enrollment
Adjusted Odds Ratio for 90-Day All-Cause Mortality per Standard Deviation Increase in the Baseline Microbial Biomarker Score
Adjusted odds ratio for death from any cause by day 90 per one standard deviation increase in the baseline microbial biomarker score. Logistic regression will adjust for prespecified clinical covariates. Results will be reported with 95% confidence intervals. Mortality will be established using hospital records and telephone follow-up when necessary.
Measured: Within 90 days after enrollment
Percentage of Microbial Biomarker Components With Concordant Associations With Day 7 Feeding Improvement in Independent Cohorts
Percentage of evaluable components of the locked microbial biomarker showing the same direction of association with day 7 EFI improvement in the study cohort and eligible independent cohorts. The percentage will equal the number of concordant components divided by the total number of evaluable components, multiplied by 100. Results will be reported separately for each external cohort. If no cohort with comparable feeding outcomes is available, this outcome will be reported as not evaluable.
Measured: Baseline and day 7
Number of Microbial Taxa Meeting High-Priority Criteria for Subsequent Experimental Validation
Number of candidate microbial taxa assigned to the highest priority tier using prespecified criteria covering feature-selection stability, associations with feeding outcomes, cross-cohort reproducibility, and consistency with functional and metabolic profiles. Classification thresholds will be established before ranking. Species-level identities will be reported only when supported by sequencing resolution.
Measured: Baseline, days 3-5, and day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2026
- Study start15 Oct 2026 (estimated)
- Primary completion15 Oct 2027 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Enteral Feeding IntoleranceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jiancheng Zhang, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07864844
- Sponsor's protocol ID
- ZJC2026112
- Status last verified
- Oct 2026
- First submitted
- 1 Oct 2026
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gut Microbiota Structure, Functional and Metabolic Profiles, and Composite Biomarkers in ICU Adults With Refractory Enteral Feeding Intolerance: A Prospective Observational Longitudinal Cohort Study
- ClinicalTrials.gov ID
- NCT07864844
- Acronym / sponsor ID
- ZJC2026112
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyUniversity, hospital or other
- Study start
- 15 Oct 2026 (estimated)
- Primary completion
- 15 Oct 2027 (estimated)
- Study completion
- 30 Dec 2027 (estimated)
- First posted
- 8 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Some adults in the intensive care unit (ICU) cannot receive enough nutrition through a feeding tube because of persistent digestive problems, even after standard measures to improve feeding. This condition is called refractory enteral feeding intolerance. The community of microorganisms living in the gut, known as the gut microbiota, and the substances produced by these microorganisms and the body may be associated with feeding tolerance and recovery.
This prospective observational study will enroll approximately 180 adults with refractory enteral feeding intolerance at a single hospital. It aims to describe changes in their gut microbiota and metabolic profiles over time and identify combinations of microbial markers associated with improved feeding tolerance and adequate nutritional intake.
Stool samples or rectal swabs will be collected at enrollment, on days 3-5 and day 7, and, when feasible, near the end of the ICU stay. The samples will be used to examine the types of microorganisms present. Selected samples will also be analyzed for metabolic substances. Clinical information about nutrition, digestive symptoms, medications, illness severity, and treatments will be collected. Participants will be followed for up to 90 days to assess survival and unplanned hospital readmissions.
The study will examine whether microbial and metabolic patterns provide additional information about feeding improvement by day 7 beyond routine clinical assessments. Where suitable public datasets are available, findings will also be evaluated in other patient groups.
Participants will continue to receive usual medical care. The study does not assign treatments or change feeding decisions. Its findings may help guide future research on feeding intolerance, but participants are not expected to receive a direct medical benefit from taking part.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ICU Adults With Refractory Enteral Feeding Intolerance | – | Other: Naturally Occurring Exposures |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adults aged 18 years or older receiving care in the ICU at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, who have refractory enteral feeding intolerance (rEFI). Eligible patients remain unable to achieve an enteral energy intake of 20 kcal/kg/day despite 72 consecutive hours of feeding strategy adjustments and standard measures, including prokinetic medications. Patients will be enrolled consecutively if they meet all eligibility criteria, can provide a spontaneously passed stool sample or safely undergo rectal swab collection within the baseline sampling window, and provide written informed consent personally or through a legally authorized representative.
Key inclusion criteria (5 listed)
- Age ≥18 years.
- Receiving care in the ICU at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology.
- Meeting the protocol-defined criteria for refractory enteral feeding intolerance (rEFI): inability to achieve an enteral energy intake of 20 kcal/kg/day despite 72 consecutive hours of feeding strategy adjustments and standard measures, including prokinetic medications.
- A spontaneously passed stool sample can be obtained, or a rectal swab can be safely collected, within the permitted baseline sampling window.
- Written informed consent provided by the participant or their legally authorized representative. Participants who regain decision-making capacity will be informed again and asked to consent to continued participation.
Key exclusion criteria (5 listed)
- Pregnancy or reasonable grounds for the investigator to suspect pregnancy. Active inflammatory bowel disease, major gastrointestinal surgery, or any other condition within the past 3 months that significantly alters intestinal anatomy and affects interpretation of the study findings.
- Receipt of fecal microbiota transplantation before ICU admission.
- Active gastrointestinal bleeding, severe coagulopathy, anorectal surgery or lesions, or other conditions that make rectal swab collection unsafe, together with an inability to obtain a spontaneously passed stool sample within the specified sampling window.
- Expected death within 24 hours, with informed consent and baseline procedures unable to be completed without interfering with emergency care.
- Refusal to participate by the participant or their legally authorized representative, or determination by the investigator that enrollment is inappropriate because of concerns regarding safety, adherence to study procedures, or data validity.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Naturally Occurring ExposuresSerial stool samples or rectal swabs will be collected at enrollment, on days 3-5 and day 7, and, when feasible, before ICU discharge or death. Gut microbiota composition will be assessed using 16S rRNA gene sequencing. A prespecified subset of samples will undergo untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomic analysis. These assessments are performed for research purposes and will not guide treatment or feeding decisions. All participants will receive usual clinical care. | Other | ICU Adults With Refractory Enteral Feeding Intolerance |
Primary outcome
Area Under the ROC Curve of a Locked Baseline Microbial Biomarker Comprising at Least 15 Taxonomic Units for Feeding Intolerance Improvement by Day 7
Time frame: Baseline (within 48 hours of T0) and day 7
The area under the receiver operating characteristic curve (AUC) will measure the ability of a locked composite microbial biomarker comprising at least 15 taxonomic units to distinguish participants with and without enteral feeding intolerance (EFI) improvement by day 7. The biomarker will be developed from baseline 16S rRNA gene sequencing data using participant-level nested cross-validation. All preprocessing, feature selection, and model tuning will occur within training folds. EFI improvement is defined as achieving an enteral energy intake of at least 20 kcal/kg/day with no reduction or discontinuation of feeding due to gastrointestinal intolerance for 24 consecutive hours. An AUC of 0.5 indicates chance-level discrimination, and an AUC of 1.0 indicates perfect discrimination.
10 secondary outcomes
Change in Gut Microbiota α Diversity Index From Baseline to Day 7
Time frame: Baseline (within 48 hours of T0) and day 7
Bray-Curtis Dissimilarity Between Baseline and Day 7 Gut Microbiota Samples
Time frame: Baseline (within 48 hours of T0) and day 7.
Number of Fecal Metabolite Features With Significant Changes From Baseline to Day 7
Time frame: Baseline (within 48 hours of T0) and day 7
Number of Predicted Microbial Functional Pathways With Significant Changes From Baseline to Day 7
Time frame: Baseline (within 48 hours of T0) and day 7
Change in Cross-Validated AUC After Adding the Baseline Microbial Biomarker to a Clinical Model for Day 7 Feeding Intolerance Improvement
Time frame: Baseline (within 48 hours of T0) and day 7
Change in Cross-Validated AUC After Adding the Baseline Microbial Biomarker to a Clinical Model for Enteral Energy Target Achievement by Day 7
Time frame: Within 7 days after enrollment
Adjusted Odds Ratio for 28-Day All-Cause Mortality per Standard Deviation Increase in the Baseline Microbial Biomarker Score
Time frame: Within 28 days after enrollment
Adjusted Odds Ratio for 90-Day All-Cause Mortality per Standard Deviation Increase in the Baseline Microbial Biomarker Score
Time frame: Within 90 days after enrollment
Percentage of Microbial Biomarker Components With Concordant Associations With Day 7 Feeding Improvement in Independent Cohorts
Time frame: Baseline and day 7
Number of Microbial Taxa Meeting High-Priority Criteria for Subsequent Experimental Validation
Time frame: Baseline, days 3-5, and day 7
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2026.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Refractory Enteral Feeding Intolerance and Gut Microbiota, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 8 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jiancheng Zhang (8613554105815, zhjcheng1@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the ROC Curve of a Locked Baseline Microbial Biomarker Comprising at Least 15 Taxonomic Units for Feeding Intolerance Improvement by Day 7 (time frame: Baseline (within 48 hours of T0) and day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2026.