xml: <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/NCT06025760</url>
    </required_header>
    <id_info>
      <org_study_id>IRB#9659</org_study_id>
      <nct_id>NCT06025760</nct_id>
    </id_info>
    <brief_title>Evaluation of Diaphragmatic Function and Quadriceps Muscle Thickness in Patients Receiving High Protein Nutrition</brief_title>
    <official_title>Evaluation of Diaphragmatic Function and Quadriceps Muscle Thickness Using Ultrasonography in Critically Ill Mechanically Ventilated Patients Receiving High Protein Nutrition</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Zagazig University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Zagazig 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>
        Different Protein Doses' Effect on Diaphragmatic Function and Quadriceps Thickness&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Nutrition therapy is no longer a support method for critically ill patients but is considered&#xD;
        an important treatment measure. Increasing the protein and energy available to patients in&#xD;
        the intensive care unit (ICU) reduces infection and complications, increases ventilator-free&#xD;
        days, increases long-term physical recovery, and lowers patient mortality Among critically&#xD;
        ill patients, protein is the most important macronutrient because it promotes healing,&#xD;
        improves immune function, and helps patients maintain their lean body mass. Growing evidence&#xD;
        has shown that adequate protein intake may be more important than caloric intake in the body.&#xD;
        In addition, reaching at least 80% of the prescribed protein intake rather than energy intake&#xD;
        is related to improved survival rates in ICU patients.&#xD;
  &#xD;
        Muscular atrophy is a common feature in patients with intensive care unit-acquired weakness&#xD;
        (ICU-AW), and it can start in the early stages of critical illness (within hours of onset of&#xD;
        the disease). Its development has been related to the acute inflammatory process and&#xD;
        immobilization. Factors such as age, medications, comorbidities, nutrition, and nervous, and&#xD;
        muscular damage before critical illness can contribute to the extent of atrophy and the&#xD;
        muscular and functional recovery capacity.&#xD;
  &#xD;
        It was believed that perhaps the respiratory muscles in humans were spared any loss of muscle&#xD;
        protein during starvation because of their constant activity. In a necropsy study designed to&#xD;
        assess the diaphragm in health and disease, it was found that alterations in body weight and&#xD;
        muscularity profoundly affect the diaphragm muscle mass.&#xD;
  &#xD;
        Mechanical ventilation (MV) is the most important life-sustaining measure for critically ill&#xD;
        patients, Even if the MV is maintained for a short time, diaphragm fatigue may also occur&#xD;
        owing to atrophy or decreased contractile function, which is known as ventilator-induced&#xD;
        diaphragm dysfunction (VIDD). Pathophysiological changes of VIDD include muscle atrophy,&#xD;
        structural damage, and fiber-type transformation and remodeling.VIDD is the main factor&#xD;
        contributing to difficult weaning from long-term MV in critically ill patients. Prolonging&#xD;
        the time of MV is associated with an increased risk of complications, long-term dysfunction,&#xD;
        and death.&#xD;
  &#xD;
        Muscles of the lower limb are more prone to early atrophy as they are weight-bearing compared&#xD;
        to the muscles of the upper limb as shown in previous studies. The authors showed that the&#xD;
        size of the flexor compartment of the elbow did not show any change in the first 10 days of&#xD;
        admission, whereas the size of the anterior compartment muscles of the lower limb showed a&#xD;
        greater decrease in thickness within the first 5 days. Thus, these muscles make a good choice&#xD;
        for muscle mass assessment.&#xD;
  &#xD;
        Point-of-care ultrasound (POCUS) is rapid, accurate, repeatable, nonexpensive, noninvasive,&#xD;
        and without the risk of radiation. It can visualize a large muscle area and deeper-located&#xD;
        muscles. It can be used in both stable and unstable patients. Performing repeated ultrasound&#xD;
        examinations in critical patients is essential and improves the overall sensitivity of the&#xD;
        examination, which has become a standard of care in critical care.&#xD;
  &#xD;
        One of the unsolved problems for a reliable definition of protein goals is the optimal intake&#xD;
        timing to reach predefined therapeutic goals. European Society for Clinical Nutrition and&#xD;
        Metabolism (ESPEN) 2009 recommended protein dose to be 1.2 - 1.5 gm /kg/day, while recent&#xD;
        ESPEN 2019 guidelines recommend a dose of 1.3 gm/kg/day. On the other hand, the American&#xD;
        Society for Parenteral and Enteral Nutrition (ASPEN) 2016 and ASPEN 2022 recommend a dose of&#xD;
        1.2- 2 gm/kg/day.&#xD;
  &#xD;
        Generally, it is well known that patients in the acute phase (ebb phase) of the stress&#xD;
        response are less capable of utilizing nutrients, thereby implying that early high-dose&#xD;
        protein administration might not be beneficial. In the later phase (flow phase) of metabolic&#xD;
        stress, insulin sensitivity gradually improves, and the human body's capability to metabolize&#xD;
        exogenous substrates increases accordingly.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">November 1, 2024</completion_date>
    <primary_completion_date type="Anticipated">October 1, 2024</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>
      <intervention_model_description>Critically ill mechanically ventilated patients will receive protein of 2 gm/kg/day in the interventional group. Critically ill mechanically ventilated patients will receive protein of 1.2 gm/kg/day in the control group.</intervention_model_description>
      <primary_purpose>Other</primary_purpose>
      <masking>Double (Care Provider, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>To assess the effect of different protein doses (1.2 gm/kg per day versus 2 gm/kg per day ) on diaphragmatic muscle function in mechanically ventilated patients in ICU for 4 weeks.</measure>
      <time_frame>from time of ICU admission on day 0,then on days 3, 5, 7, then weekly till the fourth week.</time_frame>
      <description>assessment of the effect of different protein doses per day on diaphragmatic muscle function in mechanically ventilated patients using ultrasound, the following data will be assessed:&#xD;
  Diaphragm thickness (mm) on days (0, 3, 5, and 7 from ICU admission then weekly till the fourth week ).&#xD;
  Diaphragm thickening fraction on the day (0, 3, 5, 7 then weekly till the fourth week )&#xD;
  Diaphragm excursion during the weaning trial during spontaneous breathing trial (SBT).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>To assess the effect of different protein doses (1.2 gm/kg per day versus 2 gm/kg per day ) on Quadriceps muscle thickness(mm) in mechanically ventilated patients in ICU for 4 weeks.</measure>
      <time_frame>from time of ICU admission on day 0, then on days 3, 5, 7, then weekly till the fourth week</time_frame>
      <description>Assessment of the effect of different protein doses per day on quadriceps muscle layer thickness (mm) in mechanically ventilated patients in ICU using ultrasound, the following data will be assessed :&#xD;
  Quadriceps muscle layer thickness on the day (0, 3, 5, 7, from ICU admission then weekly till the fourth week )</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">32</enrollment>
    <condition>ICU Acquired Weakness</condition>
    <arm_group>
      <arm_group_label>Interventional group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Mechanically ventilated patients will receive a nutritional caloric intake of 25-30 kcal/kg/day with a high protein dose of 2 gm protein /kg/day within 24 hours of ICU admission.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>patients will receive a nutritional caloric intake of 25-30 kcal/kg/day with a standard protein dose of 1.2 gm protein /kg/day within 24 hours of ICU admission.</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>patients who will receive 2 gm protein/kg/day will be evaluated by ultrasound for diaphragmatic function and quadriceps muscle thickness</intervention_name>
      <description>All patients after ICU admission will be started enteral nutrition through a nasogastric tube within 24-48 hours. The target caloric intake is 25-30 kcal/kg/day. patients in the interventional group will receive 2 gm protein/kg/day, while patients in the control group will receive 1.2 gm protein/kg/day. Quadriceps thickness and Diaphragm thickening fraction will be assessed by ultrasound from the time of admission on days 0, 3, 5, and 7 then weekly till the fourth week.</description>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_label>Interventional group</arm_group_label>
      <other_name>patients who will receive 1.2 gm protein/kg/day will be evaluated by ultrasound for diaphragmatic function and quadriceps muscle thickness in</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  • Acceptance of the first-degree relatives.&#xD;
  &#xD;
                 -  Critically ill patients: patients with a life-threatening condition that requires&#xD;
                    pharmacological and/or mechanical support of vital organ functions without which&#xD;
                    death would be imminent.&#xD;
  &#xD;
                 -  Patients anticipated to be mechanically ventilated for ≥ 48 hours&#xD;
  &#xD;
                 -  Patients who expected ICU stay ≥ 4 weeks&#xD;
  &#xD;
                 -  Patients aged between 18 - 60 years of both sexes.&#xD;
  &#xD;
                 -  Patient nutrition risk screening (NRS 2002) score ≥ 3&#xD;
  &#xD;
                 -  Patient BMI less than 35&#xD;
  &#xD;
                 -  No contraindication to early enteral nutrition.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  • Patient with Trauma to both lower extremities, diaphragm disease (trauma,&#xD;
               immobilization….), myopathy, and moderate to severe hepatic insufficiency.&#xD;
  &#xD;
                 -  Patient receiving steroids.&#xD;
  &#xD;
                 -  Patient on renal replacement therapy.&#xD;
  &#xD;
                 -  Prior MV before admission.&#xD;
  &#xD;
                 -  Pregnant.&#xD;
  &#xD;
                 -  Patient with neuromuscular disease, spinal cord injury, thoracic deformity, and&#xD;
                    respiratory restriction.&#xD;
  &#xD;
                 -  Patients require muscle paralysis on MV.&#xD;
  &#xD;
                 -  Patients require high dose inotrope or vasopressor.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>60 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Ghada Abdelrazik, professor</last_name>
      <role>Study Chair</role>
      <affiliation>Professor of anesthesia, intensive care and pain managment</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Neven Gamil, professor</last_name>
      <role>Study Chair</role>
      <affiliation>Professor of anesthesia, intensive care and pain managment</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Naglaa Abdelhaleem, Lecturer</last_name>
      <role>Study Chair</role>
      <affiliation>lecturer of anesthesia, intensive care and pain managment</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Ayman Amer, professor</last_name>
      <role>Study Chair</role>
      <affiliation>Professor of diagnostic radiology</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Mahmoud Aboulaban, A. Lecturer</last_name>
      <phone>01013015577</phone>
      <email>mahmoudaboulaban@gmail.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Naglaa Abdelhaleem, MD</last_name>
      <phone>01003103036</phone>
      <email>nogaahmedkareem.fa@gmail.com</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>December 6, 2022</study_first_submitted>
    <study_first_submitted_qc>September 2, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 6, 2023</study_first_posted>
    <last_update_submitted>September 13, 2023</last_update_submitted>
    <last_update_submitted_qc>September 13, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Zagazig University</investigator_affiliation>
      <investigator_full_name>Naglaa Fathy Abdelhaleem Abdelhaleem</investigator_full_name>
      <investigator_title>Lecturer of anesthesia and ICU</investigator_title>
    </responsible_party>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>Not decided yet</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06025760
  org study id: IRB#9659
  nct id: NCT06025760
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  Different Protein Doses' Effect on Diaphragmatic Function and Quadriceps Thickness
  Nutrition therapy is no longer a support method for critically ill patients but is considered
        an important treatment measure. Increasing the protein and energy available to patients in
        the intensive care unit (ICU) reduces infection and complications, increases ventilator-free
        days, increases long-term physical recovery, and lowers patient mortality Among critically
        ill patients, protein is the most important macronutrient because it promotes healing,
        improves immune function, and helps patients maintain their lean body mass. Growing evidence
        has shown that adequate protein intake may be more important than caloric intake in the body.
        In addition, reaching at least 80% of the prescribed protein intake rather than energy intake
        is related to improved survival rates in ICU patients.
  
        Muscular atrophy is a common feature in patients with intensive care unit-acquired weakness
        (ICU-AW), and it can start in the early stages of critical illness (within hours of onset of
        the disease). Its development has been related to the acute inflammatory process and
        immobilization. Factors such as age, medications, comorbidities, nutrition, and nervous, and
        muscular damage before critical illness can contribute to the extent of atrophy and the
        muscular and functional recovery capacity.
  
        It was believed that perhaps the respiratory muscles in humans were spared any loss of muscle
        protein during starvation because of their constant activity. In a necropsy study designed to
        assess the diaphragm in health and disease, it was found that alterations in body weight and
        muscularity profoundly affect the diaphragm muscle mass.
  
        Mechanical ventilation (MV) is the most important life-sustaining measure for critically ill
        patients, Even if the MV is maintained for a short time, diaphragm fatigue may also occur
        owing to atrophy or decreased contractile function, which is known as ventilator-induced
        diaphragm dysfunction (VIDD). Pathophysiological changes of VIDD include muscle atrophy,
        structural damage, and fiber-type transformation and remodeling.VIDD is the main factor
        contributing to difficult weaning from long-term MV in critically ill patients. Prolonging
        the time of MV is associated with an increased risk of complications, long-term dysfunction,
        and death.
  
        Muscles of the lower limb are more prone to early atrophy as they are weight-bearing compared
        to the muscles of the upper limb as shown in previous studies. The authors showed that the
        size of the flexor compartment of the elbow did not show any change in the first 10 days of
        admission, whereas the size of the anterior compartment muscles of the lower limb showed a
        greater decrease in thickness within the first 5 days. Thus, these muscles make a good choice
        for muscle mass assessment.
  
        Point-of-care ultrasound (POCUS) is rapid, accurate, repeatable, nonexpensive, noninvasive,
        and without the risk of radiation. It can visualize a large muscle area and deeper-located
        muscles. It can be used in both stable and unstable patients. Performing repeated ultrasound
        examinations in critical patients is essential and improves the overall sensitivity of the
        examination, which has become a standard of care in critical care.
  
        One of the unsolved problems for a reliable definition of protein goals is the optimal intake
        timing to reach predefined therapeutic goals. European Society for Clinical Nutrition and
        Metabolism (ESPEN) 2009 recommended protein dose to be 1.2 - 1.5 gm /kg/day, while recent
        ESPEN 2019 guidelines recommend a dose of 1.3 gm/kg/day. On the other hand, the American
        Society for Parenteral and Enteral Nutrition (ASPEN) 2016 and ASPEN 2022 recommend a dose of
        1.2- 2 gm/kg/day.
  
        Generally, it is well known that patients in the acute phase (ebb phase) of the stress
        response are less capable of utilizing nutrients, thereby implying that early high-dose
        protein administration might not be beneficial. In the later phase (flow phase) of metabolic
        stress, insulin sensitivity gradually improves, and the human body's capability to metabolize
        exogenous substrates increases accordingly.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Critically ill mechanically ventilated patients will receive protein of 2 gm/kg/day in the interventional group. Critically ill mechanically ventilated patients will receive protein of 1.2 gm/kg/day in the control group.
  primary purpose: Other
  masking: Double (Care Provider, Outcomes Assessor)
  measure: To assess the effect of different protein doses (1.2 gm/kg per day versus 2 gm/kg per day ) on diaphragmatic muscle function in mechanically ventilated patients in ICU for 4 weeks.
  time frame: from time of ICU admission on day 0,then on days 3, 5, 7, then weekly till the fourth week.
  description: assessment of the effect of different protein doses per day on diaphragmatic muscle function in mechanically ventilated patients using ultrasound, the following data will be assessed:
  Diaphragm thickness (mm) on days (0, 3, 5, and 7 from ICU admission then weekly till the fourth week ).
  Diaphragm thickening fraction on the day (0, 3, 5, 7 then weekly till the fourth week )
  Diaphragm excursion during the weaning trial during spontaneous breathing trial (SBT).
  measure: To assess the effect of different protein doses (1.2 gm/kg per day versus 2 gm/kg per day ) on Quadriceps muscle thickness(mm) in mechanically ventilated patients in ICU for 4 weeks.
  time frame: from time of ICU admission on day 0, then on days 3, 5, 7, then weekly till the fourth week
  description: Assessment of the effect of different protein doses per day on quadriceps muscle layer thickness (mm) in mechanically ventilated patients in ICU using ultrasound, the following data will be assessed :
  Quadriceps muscle layer thickness on the day (0, 3, 5, 7, from ICU admission then weekly till the fourth week )
  arm group label: Interventional group
  arm group type: Active Comparator
  description: Mechanically ventilated patients will receive a nutritional caloric intake of 25-30 kcal/kg/day with a high protein dose of 2 gm protein /kg/day within 24 hours of ICU admission.
  arm group label: Control group
  arm group type: Placebo Comparator
  description: patients will receive a nutritional caloric intake of 25-30 kcal/kg/day with a standard protein dose of 1.2 gm protein /kg/day within 24 hours of ICU admission.
  intervention type: Other
  intervention name: patients who will receive 2 gm protein/kg/day will be evaluated by ultrasound for diaphragmatic function and quadriceps muscle thickness
  description: All patients after ICU admission will be started enteral nutrition through a nasogastric tube within 24-48 hours. The target caloric intake is 25-30 kcal/kg/day. patients in the interventional group will receive 2 gm protein/kg/day, while patients in the control group will receive 1.2 gm protein/kg/day. Quadriceps thickness and Diaphragm thickening fraction will be assessed by ultrasound from the time of admission on days 0, 3, 5, and 7 then weekly till the fourth week.
  arm group label: Control group
  arm group label: Interventional group
  other name: patients who will receive 1.2 gm protein/kg/day will be evaluated by ultrasound for diaphragmatic function and quadriceps muscle thickness in
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 60 Years
  healthy volunteers: No
  last name: Ghada Abdelrazik, professor
  role: Study Chair
  affiliation: Professor of anesthesia, intensive care and pain managment
  last name: Neven Gamil, professor
  role: Study Chair
  affiliation: Professor of anesthesia, intensive care and pain managment
  last name: Naglaa Abdelhaleem, Lecturer
  role: Study Chair
  affiliation: lecturer of anesthesia, intensive care and pain managment
  last name: Ayman Amer, professor
  role: Study Chair
  affiliation: Professor of diagnostic radiology
  last name: Mahmoud Aboulaban, A. Lecturer
  phone: 01013015577
  email: mahmoudaboulaban@gmail.com
  last name: Naglaa Abdelhaleem, MD
  phone: 01003103036
  email: nogaahmedkareem.fa@gmail.com
  responsible party type: Principal Investigator
  investigator affiliation: Zagazig University
  investigator full name: Naglaa Fathy Abdelhaleem Abdelhaleem
  investigator title: Lecturer of anesthesia and ICU
  sharing ipd: No
  ipd description: Not decided yet