<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04443335</url>
  </required_header>
  <id_info>
    <org_study_id>QYFYKYLL761311920</org_study_id>
    <nct_id>NCT04443335</nct_id>
  </id_info>
  <brief_title>Comparison of Continuous Feeding and Sequential Feeding on Gut Microbiota and Metabolomics in Critically Ill Patients</brief_title>
  <official_title>Comparison of Continuous Feeding and Sequential Feeding on Gut Microbiota and Metabolomics in Critically Ill Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Qingdao University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Qingdao University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Continuous feeding is the most popular enteral feeding mode in the ICU because of its lower&#xD;
      nursing burden and theoretically better intestinal toleration. However, continuous feeding is&#xD;
      nonphysiological. We proposed a feeding mode called sequential feeding, as it utilizes a&#xD;
      combination of continuous feeding in the beginning, time-restricted feeding in the second&#xD;
      stage, and oral feeding at last.&#xD;
&#xD;
      The gut microbiota plays a critical role in human health due to its many useful functions.&#xD;
      Not only dietary structure but also eating mode (eating time for example) influenced the gut&#xD;
      microbiota in a healthy population. Therefore, we think this new feeding mode, sequential&#xD;
      feeding, also has different influences on gut microbiota and metabolomics in critically ill&#xD;
      patients compared to continuous feeding.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Nutrition is an important part of therapy for critically ill patients. Continuous feeding is&#xD;
      the most popular enteral feeding mode in the ICU because of its lower nursing burden and&#xD;
      theoretically better intestinal toleration. However, continuous feeding is nonphysiological.&#xD;
      In our opinion, feeding mode should be changed according to gastrointestinal function and&#xD;
      disease progression; one singe feeding mode is not always suitable for critically ill&#xD;
      patients. We proposed a feeding mode called sequential feeding, as it utilizes a combination&#xD;
      of continuous feeding in the beginning, time-restricted feeding in the second stage, and oral&#xD;
      feeding at last.&#xD;
&#xD;
      The gut microbiota plays a critical role in human health due to its many useful functions,&#xD;
      such as metabolism, vitamin metabolism, and maintenance of the intestinal barrier and immune&#xD;
      system. Not only dietary structure but also eating mode (eating time for example) influenced&#xD;
      the gut microbiota in a healthy population. Therefore, we think this new feeding mode,&#xD;
      sequential feeding, also has different influences on gut microbiota and metabolomics in&#xD;
      critically ill patients compared to continuous feeding.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2, 2020</start_date>
  <completion_date type="Actual">June 28, 2022</completion_date>
  <primary_completion_date type="Actual">June 28, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Shannon index</measure>
    <time_frame>at the time point of 7th feeding day after achieving ≥80% of the nutrition target calories</time_frame>
    <description>Shannon index is a paramater of α diversity in gut microbiota Full-length 16S rRNA gene sequencing analysis using QIIME software</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>bacteria bundance</measure>
    <time_frame>at the time point of 7th feeding day after achieving ≥80% of the nutrition target calories</time_frame>
    <description>It is a paramater of amount of bactera by Full-length 16S rRNA gene sequencing analysis using QIIME software</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>numbers of compounds</measure>
    <time_frame>at the time point of 7th feeding day after achieving ≥80% of the nutrition target calories</time_frame>
    <description>it is a paramater by untargeted metabolomics analysis</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">158</enrollment>
  <condition>Feeding Behavior</condition>
  <arm_group>
    <arm_group_label>continuous feeding</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>The total amount of every days' Enteral Nutritional Suspension was fed at constant speed for 24h</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sequential feeding</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This feeding mode utilizes a combination of continuous feeding in the beginning, time-restricted feeding in the second stage and oral feeding in the last stage</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>continous feeding</intervention_name>
    <description>At the beginning, all the patients received continuous feeding. After achieving ≥80% of the nutrition target calories (25-30 kcal/kg/d) through continuous feeding, the patients were randomly assigned into the sequential feeding (SF) group or the continuous feeding (CF) group with a random number table. Patients in the CF group received continuous feeding with constant velocity by enteral feeding pump over one day.</description>
    <arm_group_label>continuous feeding</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>sequential feeding</intervention_name>
    <description>At the beginning, all the patients received continuous feeding. After achieving ≥80% of the nutrition target calories (25-30 kcal/kg/d) through continuous feeding, the patients were randomly assigned into the sequential feeding (SF) group or the continuous feeding (CF) group with a random number table. In the SF group, continuous feeding was changed into time-restricted feeding. The total daily dosage of enteral nutrition was equally distributed during three time periods at 7-9:00, 11-13:00 and 17-19:00. Other times of the day were fasting times. Enteral nutritional suspension in each time period was administered at a uniform rate within two hours by an enteral feeding pump.</description>
    <arm_group_label>sequential feeding</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        ●Patients newly admitted to the ICU and fed through gastric tubes&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with the ability to eat orally at admission&#xD;
&#xD;
          -  Patients with diabetes or gastrointestinal disease&#xD;
&#xD;
          -  Patients who are unable to tolerate enteral feeding&#xD;
&#xD;
          -  An estimated feeding time of less than 7 days&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bo Yao, phD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The affiliated hospital of Qingdao</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The affiliated hospital of qingdao university</name>
      <address>
        <city>Qingdao</city>
        <state>Shan Dong Province</state>
        <zip>266000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <results_reference>
    <citation>McClave SA, Taylor BE, Martindale RG, Warren MM, Johnson DR, Braunschweig C, McCarthy MS, Davanos E, Rice TW, Cresci GA, Gervasio JM, Sacks GS, Roberts PR, Compher C; Society of Critical Care Medicine; American Society for Parenteral and Enteral Nutrition. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr. 2016 Feb;40(2):159-211. doi: 10.1177/0148607115621863. No abstract available. Erratum In: JPEN J Parenter Enteral Nutr. 2016 Nov;40(8):1200.</citation>
    <PMID>26773077</PMID>
  </results_reference>
  <results_reference>
    <citation>Singer P, Blaser AR, Berger MM, Alhazzani W, Calder PC, Casaer MP, Hiesmayr M, Mayer K, Montejo JC, Pichard C, Preiser JC, van Zanten ARH, Oczkowski S, Szczeklik W, Bischoff SC. ESPEN guideline on clinical nutrition in the intensive care unit. Clin Nutr. 2019 Feb;38(1):48-79. doi: 10.1016/j.clnu.2018.08.037. Epub 2018 Sep 29.</citation>
    <PMID>30348463</PMID>
  </results_reference>
  <results_reference>
    <citation>Lynch SV, Pedersen O. The Human Intestinal Microbiome in Health and Disease. N Engl J Med. 2016 Dec 15;375(24):2369-2379. doi: 10.1056/NEJMra1600266. No abstract available.</citation>
    <PMID>27974040</PMID>
  </results_reference>
  <results_reference>
    <citation>McDonald D, Ackermann G, Khailova L, Baird C, Heyland D, Kozar R, Lemieux M, Derenski K, King J, Vis-Kampen C, Knight R, Wischmeyer PE. Extreme Dysbiosis of the Microbiome in Critical Illness. mSphere. 2016 Aug 31;1(4):e00199-16. doi: 10.1128/mSphere.00199-16. eCollection 2016 Jul-Aug.</citation>
    <PMID>27602409</PMID>
  </results_reference>
  <results_reference>
    <citation>Kaczmarek JL, Thompson SV, Holscher HD. Complex interactions of circadian rhythms, eating behaviors, and the gastrointestinal microbiota and their potential impact on health. Nutr Rev. 2017 Sep 1;75(9):673-682. doi: 10.1093/nutrit/nux036.</citation>
    <PMID>28938796</PMID>
  </results_reference>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>June 21, 2020</study_first_submitted>
  <study_first_submitted_qc>June 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>November 9, 2022</last_update_submitted>
  <last_update_submitted_qc>November 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Qingdao University</investigator_affiliation>
    <investigator_full_name>Bo Yao,phD</investigator_full_name>
    <investigator_title>Clinician of critical care medicine, principal investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Critical Illness</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>connect to corresponding author by email after paper publication</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>connect to corresponding author by email after paper publication</ipd_time_frame>
    <ipd_access_criteria>by appropriate reasons</ipd_access_criteria>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04443335
org study id: QYFYKYLL761311920
nct id: NCT04443335
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Continuous feeding is the most popular enteral feeding mode in the ICU because of its lower
      nursing burden and theoretically better intestinal toleration. However, continuous feeding is
      nonphysiological. We proposed a feeding mode called sequential feeding, as it utilizes a
      combination of continuous feeding in the beginning, time-restricted feeding in the second
      stage, and oral feeding at last.

      The gut microbiota plays a critical role in human health due to its many useful functions.
      Not only dietary structure but also eating mode (eating time for example) influenced the gut
      microbiota in a healthy population. Therefore, we think this new feeding mode, sequential
      feeding, also has different influences on gut microbiota and metabolomics in critically ill
      patients compared to continuous feeding.
Nutrition is an important part of therapy for critically ill patients. Continuous feeding is
      the most popular enteral feeding mode in the ICU because of its lower nursing burden and
      theoretically better intestinal toleration. However, continuous feeding is nonphysiological.
      In our opinion, feeding mode should be changed according to gastrointestinal function and
      disease progression; one singe feeding mode is not always suitable for critically ill
      patients. We proposed a feeding mode called sequential feeding, as it utilizes a combination
      of continuous feeding in the beginning, time-restricted feeding in the second stage, and oral
      feeding at last.

      The gut microbiota plays a critical role in human health due to its many useful functions,
      such as metabolism, vitamin metabolism, and maintenance of the intestinal barrier and immune
      system. Not only dietary structure but also eating mode (eating time for example) influenced
      the gut microbiota in a healthy population. Therefore, we think this new feeding mode,
      sequential feeding, also has different influences on gut microbiota and metabolomics in
      critically ill patients compared to continuous feeding.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Shannon index
time frame: at the time point of 7th feeding day after achieving ≥80% of the nutrition target calories
description: Shannon index is a paramater of α diversity in gut microbiota Full-length 16S rRNA gene sequencing analysis using QIIME software
measure: bacteria bundance
time frame: at the time point of 7th feeding day after achieving ≥80% of the nutrition target calories
description: It is a paramater of amount of bactera by Full-length 16S rRNA gene sequencing analysis using QIIME software
measure: numbers of compounds
time frame: at the time point of 7th feeding day after achieving ≥80% of the nutrition target calories
description: it is a paramater by untargeted metabolomics analysis
arm group label: continuous feeding
arm group type: Sham Comparator
description: The total amount of every days' Enteral Nutritional Suspension was fed at constant speed for 24h
arm group label: sequential feeding
arm group type: Experimental
description: This feeding mode utilizes a combination of continuous feeding in the beginning, time-restricted feeding in the second stage and oral feeding in the last stage
intervention type: Behavioral
intervention name: continous feeding
description: At the beginning, all the patients received continuous feeding. After achieving ≥80% of the nutrition target calories (25-30 kcal/kg/d) through continuous feeding, the patients were randomly assigned into the sequential feeding (SF) group or the continuous feeding (CF) group with a random number table. Patients in the CF group received continuous feeding with constant velocity by enteral feeding pump over one day.
arm group label: continuous feeding
intervention type: Behavioral
intervention name: sequential feeding
description: At the beginning, all the patients received continuous feeding. After achieving ≥80% of the nutrition target calories (25-30 kcal/kg/d) through continuous feeding, the patients were randomly assigned into the sequential feeding (SF) group or the continuous feeding (CF) group with a random number table. In the SF group, continuous feeding was changed into time-restricted feeding. The total daily dosage of enteral nutrition was equally distributed during three time periods at 7-9:00, 11-13:00 and 17-19:00. Other times of the day were fasting times. Enteral nutritional suspension in each time period was administered at a uniform rate within two hours by an enteral feeding pump.
arm group label: sequential feeding
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bo Yao, phD
role: Principal Investigator
affiliation: The affiliated hospital of Qingdao
facility: 
country: China
citation: McClave SA, Taylor BE, Martindale RG, Warren MM, Johnson DR, Braunschweig C, McCarthy MS, Davanos E, Rice TW, Cresci GA, Gervasio JM, Sacks GS, Roberts PR, Compher C; Society of Critical Care Medicine; American Society for Parenteral and Enteral Nutrition. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr. 2016 Feb;40(2):159-211. doi: 10.1177/0148607115621863. No abstract available. Erratum In: JPEN J Parenter Enteral Nutr. 2016 Nov;40(8):1200.
PMID: 26773077
citation: Singer P, Blaser AR, Berger MM, Alhazzani W, Calder PC, Casaer MP, Hiesmayr M, Mayer K, Montejo JC, Pichard C, Preiser JC, van Zanten ARH, Oczkowski S, Szczeklik W, Bischoff SC. ESPEN guideline on clinical nutrition in the intensive care unit. Clin Nutr. 2019 Feb;38(1):48-79. doi: 10.1016/j.clnu.2018.08.037. Epub 2018 Sep 29.
PMID: 30348463
citation: Lynch SV, Pedersen O. The Human Intestinal Microbiome in Health and Disease. N Engl J Med. 2016 Dec 15;375(24):2369-2379. doi: 10.1056/NEJMra1600266. No abstract available.
PMID: 27974040
citation: McDonald D, Ackermann G, Khailova L, Baird C, Heyland D, Kozar R, Lemieux M, Derenski K, King J, Vis-Kampen C, Knight R, Wischmeyer PE. Extreme Dysbiosis of the Microbiome in Critical Illness. mSphere. 2016 Aug 31;1(4):e00199-16. doi: 10.1128/mSphere.00199-16. eCollection 2016 Jul-Aug.
PMID: 27602409
citation: Kaczmarek JL, Thompson SV, Holscher HD. Complex interactions of circadian rhythms, eating behaviors, and the gastrointestinal microbiota and their potential impact on health. Nutr Rev. 2017 Sep 1;75(9):673-682. doi: 10.1093/nutrit/nux036.
PMID: 28938796
responsible party type: Principal Investigator
investigator affiliation: Qingdao University
investigator full name: Bo Yao,phD
investigator title: Clinician of critical care medicine, principal investigator
mesh term: Critical Illness
sharing ipd: Yes
ipd description: connect to corresponding author by email after paper publication
ipd info type: Study Protocol
ipd info type: Clinical Study Report (CSR)
ipd time frame: connect to corresponding author by email after paper publication
ipd access criteria: by appropriate reasons