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

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.

Study Overview

• Status: Completed
• Conditions: Enteral Nutrition
• Intervention / Treatment: Dietary supplement: Blend of amino acids; Dietary supplement: Maltodextrin only

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Garches, France, 92380
    • Hôpital Raymond Poincaré (AP-HP)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients aged 18 and over
2. Sepsis or ARDS patients: expected to stay at least 21 days in ICU (or midcare), to the opinion of the investigator
3. Informed consent signed by the patient or/and by his/her representative

Exclusion Criteria:

1. Patient with muscle mass loss due to previous hospitalization
2. Intolerance to enteral feeding
3. Patients using parenteral feeding
4. Chronic renal failure to the opinion of the investigator
5. Chronic liver disease to the opinion of the investigator
6. Cachectic patients
7. Current treatment with paralyzing drugs
8. No pacemaker or metal implants interacting with MRI and magnetic stimulation
9. Pregnant woman (known)
10. Persons without social security
11. Under guardianship
12. Currently participating or having participated in another clinical trial within 4 weeks prior to trial start
13. Patient who is expected not to comply with the study procedures, to the opinion of the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Active group; Blend of amino acids	Dietary supplement: Blend of amino acids; The product was poured in bottles containing the enteral nutrition that the patient received as standard of care.
PLACEBO_COMPARATOR: Placebo group; maltodextrin only	Dietary supplement: Maltodextrin only; The product was poured in bottles containing the enteral nutrition that the patient received as standard of care.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Nestlé
• Investigators: Principal Investigator: Djillali Annane, Pr, Raymond Poincaré Hospital, Garches, FRANCE

Publications and helpful links

General Publications

• Heming N, Carlier R, Prigent H, Mekki A, Jousset C, Lofaso F, Ambrosi X, Bounab R, Maxime V, Mansart A, Crenn P, Moine P, Foltzer F, Cuenoud B, Konz T, Corthesy J, Beaumont M, Hartweg M, Roessle C, Preiser JC, Breuille D, Annane D. Effect of an enteral amino acid blend on muscle and gut functionality in critically ill patients: a proof-of-concept randomized controlled trial. Crit Care. 2022 Nov 17;26(1):358. doi: 10.1186/s13054-022-04232-5.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2017
• Primary Completion (ACTUAL): September 30, 2019
• Study Completion (ACTUAL): December 31, 2019

Study Registration Dates

• First Submitted: October 19, 2016
• First Submitted That Met QC Criteria: November 16, 2016
• First Posted (ESTIMATE): November 21, 2016

Study Record Updates

• Last Update Posted (ACTUAL): May 2, 2022
• Last Update Submitted That Met QC Criteria: April 26, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 15.04.CLI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No