<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/NCT02968836</url>
  </required_header>
  <id_info>
    <org_study_id>15.04.CLI</org_study_id>
    <nct_id>NCT02968836</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of an Amino Acid Blend on Muscle and Gut Functionality in ICU Patients</brief_title>
  <official_title>Safety and Efficacy of an Amino Acid Blend on Muscle and Gut Functionality in ICU Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Société des Produits Nestlé (SPN)</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Société des Produits Nestlé (SPN)</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Assessment of the Safety and efficacy of an amino acid blend on muscle and gut functionality&#xD;
      in Intensive Care Unit (ICU) patients.&#xD;
&#xD;
      Since this was a proof of concept, exploratory trial, we assessed different primary outcomes&#xD;
      without hierarchy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This monocentric trial was a parallel, randomized, double-blind, controlled study. Patients&#xD;
      hospitalized in the ICU for sepsis or ARDS were enrolled.&#xD;
&#xD;
      The treatment group (n=15) was administered the study product (amino acid blend) and the&#xD;
      negative control group (=15) was administrated maltodextrin only. The mode of administration&#xD;
      was nasogastric probe.&#xD;
&#xD;
      The treatment period was 21 days. Subject were followed during stay in High care and&#xD;
      intermediate care units up to 2 months or after hospital discharge with a follow up until 12&#xD;
      months.&#xD;
&#xD;
      Recruitment stopped when 30 patients (15 in each group) reached V4.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2017</start_date>
  <completion_date type="Actual">December 31, 2019</completion_date>
  <primary_completion_date type="Actual">September 30, 2019</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>Supportive Care</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety: Renal function change</measure>
    <time_frame>60 days from the beginning of the intervention</time_frame>
    <description>Renal function will be daily assessed from urine output, serum creatinin and glomerular filtration rate</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Efficacy: muscle functionality change</measure>
    <time_frame>12 months from the beginning of the intervention (timepoints: D1, D7, D14, D21, D60, D180, D365)</time_frame>
    <description>i. Muscle (quadriceps) extension isometric strength in response to magnetic stimulation; diaphragm muscle strength in response to magnetic stimulation. Forced vital capacity and maximal inspiratory and expiratory pressures will systematically be recorded.&#xD;
ii. Loss in quadriceps muscle mass and metabolism will be measured by Magnetic resonance imaging.&#xD;
Muscle protein catabolism will be evaluated from measures of 3-methyl histidine in the 24-h urine (reported to urine creatinine).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Efficacy: gut barrier structure and functionality improvement</measure>
    <time_frame>12 months from the beginning of the intervention (timepoints: D1, D7, D14, D21, D60, D180, D365)</time_frame>
    <description>i. Enterocytes damage by measurement of I-FABP (intestinal fatty acid-binding protein) in plasma and urine.&#xD;
ii. Functional enterocyte mass by citrulline plasma concentration. iii. Gut barrier function by the translocation of bacteria based on plasma D-Lactate concentration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Efficacy: inflammatory status change</measure>
    <time_frame>12 months from the beginning of the intervention (timepoints: D1, D7, D14, D21, D60, D180, D365)</time_frame>
    <description>i. Calprotectin in feces, which is secreted by the neutrophils of the gut mucosae and is released in the gut when the mucosa is inflamed.&#xD;
ii. Acute phase protein concentration in plasma (CRP, fibrinogen, ferritin, prealbumin)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Efficacy: general recovery improvement</measure>
    <time_frame>12 months from the beginning of the intervention (timepoints: D1, D7, D14, D21, D60, D180, D365)</time_frame>
    <description>i. Length of stay (LOS) in High care and intermediate care units. ii. Time (days) free of ventilation until discharge high care. iii. Time (days) to recover on walking with or without aid</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Nutrient profiling</measure>
    <time_frame>Over 60 days from the beginning of intervention (timepoints: D1, D7, D14, D21, D60)</time_frame>
    <description>Nutrient profiling will be assessed from blood metabolomics analyses</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">35</enrollment>
  <condition>Enteral Nutrition</condition>
  <arm_group>
    <arm_group_label>Active group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Blend of amino acids</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>maltodextrin only</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Blend of amino acids</intervention_name>
    <description>The product was poured in bottles containing the enteral nutrition that the patient received as standard of care.</description>
    <arm_group_label>Active group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Maltodextrin only</intervention_name>
    <description>The product was poured in bottles containing the enteral nutrition that the patient received as standard of care.</description>
    <arm_group_label>Placebo group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients aged 18 and over&#xD;
&#xD;
          2. Sepsis or ARDS patients: expected to stay at least 21 days in ICU (or midcare), to the&#xD;
             opinion of the investigator&#xD;
&#xD;
          3. Informed consent signed by the patient or/and by his/her representative&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient with muscle mass loss due to previous hospitalization&#xD;
&#xD;
          2. Intolerance to enteral feeding&#xD;
&#xD;
          3. Patients using parenteral feeding&#xD;
&#xD;
          4. Chronic renal failure to the opinion of the investigator&#xD;
&#xD;
          5. Chronic liver disease to the opinion of the investigator&#xD;
&#xD;
          6. Cachectic patients&#xD;
&#xD;
          7. Current treatment with paralyzing drugs&#xD;
&#xD;
          8. No pacemaker or metal implants interacting with MRI and magnetic stimulation&#xD;
&#xD;
          9. Pregnant woman (known)&#xD;
&#xD;
         10. Persons without social security&#xD;
&#xD;
         11. Under guardianship&#xD;
&#xD;
         12. Currently participating or having participated in another clinical trial within 4&#xD;
             weeks prior to trial start&#xD;
&#xD;
         13. Patient who is expected not to comply with the study procedures, to the opinion of the&#xD;
             investigator&#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>Djillali Annane, Pr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Raymond Poincaré Hospital, Garches, France</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital Raymond Poincaré (AP-HP)</name>
      <address>
        <city>Garches</city>
        <zip>92380</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>October 19, 2016</study_first_submitted>
  <study_first_submitted_qc>November 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2016</study_first_posted>
  <last_update_submitted>April 26, 2022</last_update_submitted>
  <last_update_submitted_qc>April 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT02968836
org study id: 15.04.CLI
nct id: NCT02968836
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Assessment of the Safety and efficacy of an amino acid blend on muscle and gut functionality
      in Intensive Care Unit (ICU) patients.

      Since this was a proof of concept, exploratory trial, we assessed different primary outcomes
      without hierarchy.
This monocentric trial was a parallel, randomized, double-blind, controlled study. Patients
      hospitalized in the ICU for sepsis or ARDS were enrolled.

      The treatment group (n=15) was administered the study product (amino acid blend) and the
      negative control group (=15) was administrated maltodextrin only. The mode of administration
      was nasogastric probe.

      The treatment period was 21 days. Subject were followed during stay in High care and
      intermediate care units up to 2 months or after hospital discharge with a follow up until 12
      months.

      Recruitment stopped when 30 patients (15 in each group) reached V4.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Safety: Renal function change
time frame: 60 days from the beginning of the intervention
description: Renal function will be daily assessed from urine output, serum creatinin and glomerular filtration rate
measure: Efficacy: muscle functionality change
time frame: 12 months from the beginning of the intervention (timepoints: D1, D7, D14, D21, D60, D180, D365)
description: i. Muscle (quadriceps) extension isometric strength in response to magnetic stimulation; diaphragm muscle strength in response to magnetic stimulation. Forced vital capacity and maximal inspiratory and expiratory pressures will systematically be recorded.
ii. Loss in quadriceps muscle mass and metabolism will be measured by Magnetic resonance imaging.
Muscle protein catabolism will be evaluated from measures of 3-methyl histidine in the 24-h urine (reported to urine creatinine).
measure: Efficacy: gut barrier structure and functionality improvement
time frame: 12 months from the beginning of the intervention (timepoints: D1, D7, D14, D21, D60, D180, D365)
description: i. Enterocytes damage by measurement of I-FABP (intestinal fatty acid-binding protein) in plasma and urine.
ii. Functional enterocyte mass by citrulline plasma concentration. iii. Gut barrier function by the translocation of bacteria based on plasma D-Lactate concentration
measure: Efficacy: inflammatory status change
time frame: 12 months from the beginning of the intervention (timepoints: D1, D7, D14, D21, D60, D180, D365)
description: i. Calprotectin in feces, which is secreted by the neutrophils of the gut mucosae and is released in the gut when the mucosa is inflamed.
ii. Acute phase protein concentration in plasma (CRP, fibrinogen, ferritin, prealbumin)
measure: Efficacy: general recovery improvement
time frame: 12 months from the beginning of the intervention (timepoints: D1, D7, D14, D21, D60, D180, D365)
description: i. Length of stay (LOS) in High care and intermediate care units. ii. Time (days) free of ventilation until discharge high care. iii. Time (days) to recover on walking with or without aid
measure: Nutrient profiling
time frame: Over 60 days from the beginning of intervention (timepoints: D1, D7, D14, D21, D60)
description: Nutrient profiling will be assessed from blood metabolomics analyses
arm group label: Active group
arm group type: Active Comparator
description: Blend of amino acids
arm group label: Placebo group
arm group type: Placebo Comparator
description: maltodextrin only
intervention type: Dietary Supplement
intervention name: Blend of amino acids
description: The product was poured in bottles containing the enteral nutrition that the patient received as standard of care.
arm group label: Active group
intervention type: Dietary Supplement
intervention name: Maltodextrin only
description: The product was poured in bottles containing the enteral nutrition that the patient received as standard of care.
arm group label: Placebo group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Djillali Annane, Pr
role: Principal Investigator
affiliation: Raymond Poincaré Hospital, Garches, France
facility: 
country: France
responsible party type: Sponsor
sharing ipd: No