<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/NCT03777683</url>
  </required_header>
  <id_info>
    <org_study_id>970612</org_study_id>
    <nct_id>NCT03777683</nct_id>
  </id_info>
  <brief_title>Evaluation the Effects of French Maritime Pine Bark Extract on the Clinical Status in Traumatic Brain Injury Patients</brief_title>
  <official_title>Evaluation the Effects of French Maritime Pine Bark Extract Supplementation on the Inflammatory Biomarkers, Nutritional and Clinical Status in Traumatic Brain Injury Patients, in Intensive Care Unit; A Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mashhad University of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mashhad University of Medical Sciences</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>
      Introduction: Traumatic brain injury (TBI) is one of the major health and socioeconomic&#xD;
      problems in the world. Immune-enhancing enteral formula has been proven to significantly&#xD;
      reduce infection rate in TBI patient. One of the ingredients that can be used in&#xD;
      immunonutrition formulas to reduce inflammation and oxidative stress is French maritime pine&#xD;
      bark extract.&#xD;
&#xD;
      Objective: The main objective of present study is surveying the effect of French maritime&#xD;
      pine bark extract on the clinical, nutritional and inflammatory status of TBI patients as the&#xD;
      first human study in the world.&#xD;
&#xD;
      Method: this is double-blind, randomized controlled trial. Block randomization are used.&#xD;
      Intervention group will receive French maritime pine bark extract supplement (OLIGOPIN) 150&#xD;
      mg for 10 days. Control group will receive placebo for the same duration. Inflammatory status&#xD;
      (IL-6, IL- 1β, C-reactive protein) and oxidative stress status (Malondialdehyde, total&#xD;
      antioxidant capacity), at the base line, at the 5th day and at the end of the study (10th&#xD;
      day) are measured. APACHE ІІ (acute physiologic and chronic health evaluation II) for&#xD;
      assessment of clinical status of patients and Nutric questionnaires for assessment of&#xD;
      nutritional status filled out at the base line, 5th day and the end of study. SOFA&#xD;
      (sequential organ failure assessment) questionnaire for assessment of organ failure filled&#xD;
      out every other day. The mortality rate will be asked by phone within 28 days of the start of&#xD;
      the intervention. Weight, body mass index and body composition at baseline, 5th day and 10th&#xD;
      day of intervention are measured. All analyses will be conducted by initially assigned study&#xD;
      arm in an intention-to-treat analysis. The data will be expressed as mean ± SD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Randomization:&#xD;
&#xD;
      investigators randomly assign eligible patients on enrolment (1:1) to either the control&#xD;
      group or the intervention group. Randomization is stratified by site and a randomization list&#xD;
      of unique patient identifiers is generated by the study statistician using a&#xD;
      computer-generated random block size. The classification is based on age (18 to 40 and 40 to&#xD;
      65 years old), gender (male / female) and APACHEII score (0 to 35 and 35 to 71) using&#xD;
      quadruple blocks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 14, 2019</start_date>
  <completion_date type="Actual">February 20, 2020</completion_date>
  <primary_completion_date type="Actual">December 22, 2019</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>On enrolment, study nutritionist or clinicians take a consecutive sealed opaque envelope containing the unique patient identifier but not the study group, to which they remain masked. A paired set of sealed envelopes are kept in a locked cabinet in the study laboratory, label with the unique patient identifier and containing the study group allocation. These are opened by the nutritionist. Investigators, all study staff hospital attending clinical teams, and patients were masked to the study group allocation.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>change of IL-6</measure>
    <time_frame>5 and 10 days</time_frame>
    <description>Inflammatory markers</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change of IL-1β</measure>
    <time_frame>5 and 10 days</time_frame>
    <description>Inflammatory marker</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change of CRP</measure>
    <time_frame>5 and 10 days</time_frame>
    <description>Inflammatory marker</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change of Malondialdehyde</measure>
    <time_frame>5 and 10 days</time_frame>
    <description>Oxidative stress marker</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change of total anti- oxidant capacity</measure>
    <time_frame>5 and 10 days</time_frame>
    <description>anti-oxidative stress marker</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change of weight</measure>
    <time_frame>5 and 10 days</time_frame>
    <description>measurement is done via portable scale</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change of body fat percentage</measure>
    <time_frame>5 and 10 days</time_frame>
    <description>measurement is done via Bio impedance device &quot;Inbody&quot;</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change of Body mass index</measure>
    <time_frame>5 and 10 days</time_frame>
    <description>it is calculated by Equation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change of acute physiologic and chronic health evaluation II score</measure>
    <time_frame>5 and 10 days</time_frame>
    <description>The Acute Physiology and Chronic Health Evaluation (APACHE II) is a severity score and mortality estimation tool developed from a large sample of ICU patients in the United States.&#xD;
Interpretation: Score: 0-4: Death Rate (%):4, Score: 5-9:Death Rate (%):8, Score: 10-14:Death Rate (%):15, Score: 15-19:Death Rate (%):25, Score: 20-24:Death Rate (%):40, Score: 25-29:Death Rate (%):55, Score: 30-34:Death Rate (%):75. Score: ˃ 34 :Death Rate (%):85.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change of sequential organ failure assessment score</measure>
    <time_frame>1, 3, 5, 7, 9, 10 days</time_frame>
    <description>The Sequential Organ Failure Assessment (SOFA) is a morbidity severity score and mortality estimation tool developed from a large sample of ICU patients throughout the world. The SOFA was designed to focus on organ dysfunction and morbidity, with less of an emphasis on mortality prediction.&#xD;
Interpretation: Score: 0-6: Death Rate (%):&lt; 10%, Score: 7-9:Death Rate (%):15 - 20%, Score: 10-12:Death Rate (%):40 - 50%, Score: 13-14:Death Rate (%):50 - 60%, Score: 15:Death Rate (%):&gt; 80%, Score: 15-24:Death Rate (%):&gt; 90%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change of Nutric score</measure>
    <time_frame>5 and 10 days</time_frame>
    <description>The NUTRIC score (Nutrition assessment in critically ill) is a rapid assessment of nutritional state based on illness severity, age and co-morbidities.&#xD;
Sum of points: 6-10: CATEGORY: High Score. Sum of points: 0-5: CATEGORY: LOW Score High score associated with worse clinical outcomes (mortality, ventilation).These patients are the most likely to benefit from the aggressive nutrition therapy.&#xD;
LOW Score: These patients have a low malnutrition risk</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>28-day mortality</measure>
    <time_frame>28 days</time_frame>
    <description>the rate of mortality</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">67</enrollment>
  <condition>Traumatic Brain Injury</condition>
  <arm_group>
    <arm_group_label>Dietary Supplement (OLIGOPIN)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intervention group will receive French maritime pine bark extract supplement (OLIGOPIN) in the form oral capsules containing 50 mg French maritime pine bark extract plus 130 mg Microcrystalline Cellulose. OLIGOPIN powder of each capsule are dissolved in 10 ml deionized water and given to patients via gavage (3 capsule per day) for 10 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Control group will receive oral capsules containing 130 mg Microcrystalline Cellulose with 10 ml of deionized water via gavage (3 capsule per day) for 10 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Dietary Supplement (OLIGOPIN)</intervention_name>
    <description>investigators obtained ethical approval from the Research Ethics Committees of the Mashhad University of medical sciences. investigators enroll 60 patients who are admitted to ICU at hospitals of university. All eligible patients or their first degree relatives give informed consent before participating. Participants are randomly (block stratification) divided in two groups. At the first visit, baseline data are gathered and intervention group (n=30) will receive Oligopin supplement. In order to control the confounding effect of food intake, both the control and the intervention group receive the standard formulas based on their daily required energy via enteral root feeding.</description>
    <arm_group_label>Dietary Supplement (OLIGOPIN)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>investigators obtained ethical approval from the Research Ethics Committees of the Mashhad University of medical sciences. investigators enroll 60 patients who are admitted to ICU at hospitals of university. All eligible patients or their first degree relatives give informed consent before participating. Participants are randomly (block stratification) divided in two groups. At the first visit, baseline data are gathered and control group (n=30) will receive oral capsules containing 130 mg Microcrystalline Cellulose. In order to control the confounding effect of food intake, both the control and the intervention group receive the standard formulas based on their daily required energy via enteral root feeding.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Admission in ICU due to TBI2&#xD;
&#xD;
          -  18 year ≤ age ≤ 65 year&#xD;
&#xD;
          -  GCS score ˃ 8&#xD;
&#xD;
          -  Stable hemodynamic and metabolic status in the first 24 to 48 hours&#xD;
&#xD;
          -  Having enteral nutritional support&#xD;
&#xD;
          -  Fill out the informed consent form by the patient or first-degree relatives of the&#xD;
             patient&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy and lactation&#xD;
&#xD;
          -  Morbid obesity: BMI ≥ 40&#xD;
&#xD;
          -  Failure to start enteral nutrition in the first 24-48 hours&#xD;
&#xD;
          -  Suffering from autoimmune disorders and HIV/Aids&#xD;
&#xD;
          -  Suffering or having History of cancer and any liver failure&#xD;
&#xD;
          -  Receiving positive inotropic medications including Dopamine, Dobutamine and&#xD;
             Epinephrine&#xD;
&#xD;
          -  Severe and active bleeding&#xD;
&#xD;
          -  Suffering from Sepsis&#xD;
&#xD;
          -  Having history of known food allergies&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Mahsa Malekahmadi</name>
      <address>
        <city>Tehran</city>
        <country>Iran, Islamic Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Iran, Islamic Republic of</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>December 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 13, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 17, 2018</study_first_posted>
  <last_update_submitted>May 19, 2020</last_update_submitted>
  <last_update_submitted_qc>May 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 21, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mashhad University of Medical Sciences</investigator_affiliation>
    <investigator_full_name>Mahsa Malekahmadi</investigator_full_name>
    <investigator_title>principal investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <!-- 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/NCT03777683
org study id: 970612
nct id: NCT03777683
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Introduction: Traumatic brain injury (TBI) is one of the major health and socioeconomic
      problems in the world. Immune-enhancing enteral formula has been proven to significantly
      reduce infection rate in TBI patient. One of the ingredients that can be used in
      immunonutrition formulas to reduce inflammation and oxidative stress is French maritime pine
      bark extract.

      Objective: The main objective of present study is surveying the effect of French maritime
      pine bark extract on the clinical, nutritional and inflammatory status of TBI patients as the
      first human study in the world.

      Method: this is double-blind, randomized controlled trial. Block randomization are used.
      Intervention group will receive French maritime pine bark extract supplement (OLIGOPIN) 150
      mg for 10 days. Control group will receive placebo for the same duration. Inflammatory status
      (IL-6, IL- 1β, C-reactive protein) and oxidative stress status (Malondialdehyde, total
      antioxidant capacity), at the base line, at the 5th day and at the end of the study (10th
      day) are measured. APACHE ІІ (acute physiologic and chronic health evaluation II) for
      assessment of clinical status of patients and Nutric questionnaires for assessment of
      nutritional status filled out at the base line, 5th day and the end of study. SOFA
      (sequential organ failure assessment) questionnaire for assessment of organ failure filled
      out every other day. The mortality rate will be asked by phone within 28 days of the start of
      the intervention. Weight, body mass index and body composition at baseline, 5th day and 10th
      day of intervention are measured. All analyses will be conducted by initially assigned study
      arm in an intention-to-treat analysis. The data will be expressed as mean ± SD.
Randomization:

      investigators randomly assign eligible patients on enrolment (1:1) to either the control
      group or the intervention group. Randomization is stratified by site and a randomization list
      of unique patient identifiers is generated by the study statistician using a
      computer-generated random block size. The classification is based on age (18 to 40 and 40 to
      65 years old), gender (male / female) and APACHEII score (0 to 35 and 35 to 71) using
      quadruple blocks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: On enrolment, study nutritionist or clinicians take a consecutive sealed opaque envelope containing the unique patient identifier but not the study group, to which they remain masked. A paired set of sealed envelopes are kept in a locked cabinet in the study laboratory, label with the unique patient identifier and containing the study group allocation. These are opened by the nutritionist. Investigators, all study staff hospital attending clinical teams, and patients were masked to the study group allocation.
measure: change of IL-6
time frame: 5 and 10 days
description: Inflammatory markers
measure: change of IL-1β
time frame: 5 and 10 days
description: Inflammatory marker
measure: change of CRP
time frame: 5 and 10 days
description: Inflammatory marker
measure: change of Malondialdehyde
time frame: 5 and 10 days
description: Oxidative stress marker
measure: change of total anti- oxidant capacity
time frame: 5 and 10 days
description: anti-oxidative stress marker
measure: change of weight
time frame: 5 and 10 days
description: measurement is done via portable scale
measure: change of body fat percentage
time frame: 5 and 10 days
description: measurement is done via Bio impedance device "Inbody"
measure: change of Body mass index
time frame: 5 and 10 days
description: it is calculated by Equation
measure: change of acute physiologic and chronic health evaluation II score
time frame: 5 and 10 days
description: The Acute Physiology and Chronic Health Evaluation (APACHE II) is a severity score and mortality estimation tool developed from a large sample of ICU patients in the United States.
Interpretation: Score: 0-4: Death Rate (%):4, Score: 5-9:Death Rate (%):8, Score: 10-14:Death Rate (%):15, Score: 15-19:Death Rate (%):25, Score: 20-24:Death Rate (%):40, Score: 25-29:Death Rate (%):55, Score: 30-34:Death Rate (%):75. Score: ˃ 34 :Death Rate (%):85.
measure: change of sequential organ failure assessment score
time frame: 1, 3, 5, 7, 9, 10 days
description: The Sequential Organ Failure Assessment (SOFA) is a morbidity severity score and mortality estimation tool developed from a large sample of ICU patients throughout the world. The SOFA was designed to focus on organ dysfunction and morbidity, with less of an emphasis on mortality prediction.
Interpretation: Score: 0-6: Death Rate (%):< 10%, Score: 7-9:Death Rate (%):15 - 20%, Score: 10-12:Death Rate (%):40 - 50%, Score: 13-14:Death Rate (%):50 - 60%, Score: 15:Death Rate (%):> 80%, Score: 15-24:Death Rate (%):> 90%.
measure: change of Nutric score
time frame: 5 and 10 days
description: The NUTRIC score (Nutrition assessment in critically ill) is a rapid assessment of nutritional state based on illness severity, age and co-morbidities.
Sum of points: 6-10: CATEGORY: High Score. Sum of points: 0-5: CATEGORY: LOW Score High score associated with worse clinical outcomes (mortality, ventilation).These patients are the most likely to benefit from the aggressive nutrition therapy.
LOW Score: These patients have a low malnutrition risk
measure: 28-day mortality
time frame: 28 days
description: the rate of mortality
arm group label: Dietary Supplement (OLIGOPIN)
arm group type: Experimental
description: Intervention group will receive French maritime pine bark extract supplement (OLIGOPIN) in the form oral capsules containing 50 mg French maritime pine bark extract plus 130 mg Microcrystalline Cellulose. OLIGOPIN powder of each capsule are dissolved in 10 ml deionized water and given to patients via gavage (3 capsule per day) for 10 days
arm group label: Placebo
arm group type: Placebo Comparator
description: Control group will receive oral capsules containing 130 mg Microcrystalline Cellulose with 10 ml of deionized water via gavage (3 capsule per day) for 10 days.
intervention type: Dietary Supplement
intervention name: Dietary Supplement (OLIGOPIN)
description: investigators obtained ethical approval from the Research Ethics Committees of the Mashhad University of medical sciences. investigators enroll 60 patients who are admitted to ICU at hospitals of university. All eligible patients or their first degree relatives give informed consent before participating. Participants are randomly (block stratification) divided in two groups. At the first visit, baseline data are gathered and intervention group (n=30) will receive Oligopin supplement. In order to control the confounding effect of food intake, both the control and the intervention group receive the standard formulas based on their daily required energy via enteral root feeding.
arm group label: Dietary Supplement (OLIGOPIN)
intervention type: Other
intervention name: Placebo
description: investigators obtained ethical approval from the Research Ethics Committees of the Mashhad University of medical sciences. investigators enroll 60 patients who are admitted to ICU at hospitals of university. All eligible patients or their first degree relatives give informed consent before participating. Participants are randomly (block stratification) divided in two groups. At the first visit, baseline data are gathered and control group (n=30) will receive oral capsules containing 130 mg Microcrystalline Cellulose. In order to control the confounding effect of food intake, both the control and the intervention group receive the standard formulas based on their daily required energy via enteral root feeding.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
country: Iran, Islamic Republic of
responsible party type: Principal Investigator
investigator affiliation: Mashhad University of Medical Sciences
investigator full name: Mahsa Malekahmadi
investigator title: principal investigator
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
mesh term: Wounds and Injuries