Safety and Efficacy of an Amino Acid Blend on Muscle and Gut Functionality in ICU Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Safety and Efficacy of an Amino Acid Blend on Muscle and Gut Functionality in ICU Patients

Conditions
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Enteral Nutrition

Intervention / Treatment
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* Dietary Supplement: Blend of amino acids
* Dietary Supplement: Maltodextrin only


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18 and over Sepsis or ARDS patients: expected to stay at least 21 days in ICU (or midcare), to the opinion of the investigator Informed consent signed by the patient or/and by his/her representative Exclusion Criteria: Patient with muscle mass loss due to previous hospitalization Intolerance to enteral feeding Patients using parenteral feeding Chronic renal failure to the opinion of the investigator Chronic liver disease to the opinion of the investigator Cachectic patients Current treatment with paralyzing drugs No pacemaker or metal implants interacting with MRI and magnetic stimulation Pregnant woman (known) Persons without social security Under guardianship Currently participating or having participated in another clinical trial within 4 weeks prior to trial start Patient who is expected not to comply with the study procedures, to the opinion of the investigator

Ages Eligible for Study
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Minimum Age: 18 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active group<br>Blend of amino acids | Dietary Supplement: Blend of amino acids<br>* The product was poured in bottles containing the enteral nutrition that the patient received as standard of care.<br>|
| Placebo Comparator: Placebo group<br>maltodextrin only | Dietary Supplement: Maltodextrin only<br>* The product was poured in bottles containing the enteral nutrition that the patient received as standard of care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Renal function change | Renal function will be daily assessed from urine output, serum creatinin and glomerular filtration rate | 60 days from the beginning of the intervention | 
| Efficacy: muscle functionality change | 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). | 12 months from the beginning of the intervention (timepoints: D1, D7, D14, D21, D60, D180, D365) | 
| Efficacy: gut barrier structure and functionality improvement | 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 | 12 months from the beginning of the intervention (timepoints: D1, D7, D14, D21, D60, D180, D365) | 
| Efficacy: inflammatory status change | 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) | 12 months from the beginning of the intervention (timepoints: D1, D7, D14, D21, D60, D180, D365) | 
| Efficacy: general recovery improvement | 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 | 12 months from the beginning of the intervention (timepoints: D1, D7, D14, D21, D60, D180, D365) | 
| Nutrient profiling | Nutrient profiling will be assessed from blood metabolomics analyses | Over 60 days from the beginning of intervention (timepoints: D1, D7, D14, D21, D60) |