Evaluation the Effects of French Maritime Pine Bark Extract on the Clinical Status in Traumatic Brain Injury Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Traumatic Brain Injury

Intervention / Treatment
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* Dietary Supplement: Dietary Supplement (OLIGOPIN)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Admission in ICU due to TBI2 18 year ≤ age ≤ 65 year GCS score ˃ 8 Stable hemodynamic and metabolic status in the first 24 to 48 hours Having enteral nutritional support Fill out the informed consent form by the patient or first-degree relatives of the patient Exclusion Criteria: Pregnancy and lactation Morbid obesity: BMI ≥ 40 Failure to start enteral nutrition in the first 24-48 hours Suffering from autoimmune disorders and HIV/Aids Suffering or having History of cancer and any liver failure Receiving positive inotropic medications including Dopamine, Dobutamine and Epinephrine Severe and active bleeding Suffering from Sepsis Having history of known food allergies

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dietary Supplement (OLIGOPIN)<br>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 | Dietary Supplement: Dietary Supplement (OLIGOPIN)<br>* 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.<br>|
| Placebo Comparator: Placebo<br>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. | Other: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of IL-6 | Inflammatory markers | 5 and 10 days | 
| change of IL-1β | Inflammatory marker | 5 and 10 days | 
| change of CRP | Inflammatory marker | 5 and 10 days | 
| change of Malondialdehyde | Oxidative stress marker | 5 and 10 days | 
| change of total anti- oxidant capacity | anti-oxidative stress marker | 5 and 10 days | 
| change of weight | measurement is done via portable scale | 5 and 10 days | 
| change of body fat percentage | measurement is done via Bio impedance device Inbody | 5 and 10 days | 
| change of Body mass index | it is calculated by Equation | 5 and 10 days | 
| change of acute physiologic and chronic health evaluation II score | 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. | 5 and 10 days | 
| change of sequential organ failure assessment score | 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%. | 1, 3, 5, 7, 9, 10 days | 
| change of Nutric score | 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 | 5 and 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-day mortality | the rate of mortality | 28 days |