Amino Acid Nutrition for Critical Illness

(AA-ICU Trial)

Not currently recruiting at 1 trial location

Overseen By Josie Campisi, RN, CRC

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Arnold Kristof

Disqualifiers: Moribund, Life-sustaining withdrawal, Parenteral nutrition, Severe liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 48 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two methods of administering amino acids, the building blocks of proteins, to critically ill patients on ventilators in the ICU. The aim is to determine if these amino acids can aid in muscle building and faster healing. One group receives amino acids through a feeding tube using Peptamen 1.5%, while two other groups receive them directly into the bloodstream with Prosol 20% IV (an amino acid injection). This trial may suit patients on a ventilator in the ICU who are expected to require this and other intensive care for at least three more days. As an unphased trial, it offers patients the opportunity to contribute to important research that could enhance ICU care.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Peptamen 1.5 is a nutrition formula that most people can easily digest. It is often used by those who need high-calorie intake but cannot consume large amounts of food. This formula caters to specific dietary needs and typically causes few side effects when used correctly.

Conversely, Prosol 20% IV is a protein solution administered intravenously for individuals requiring extra protein. Some safety considerations exist, as some people have reported allergic reactions, including severe allergies, when using solutions like Prosol. However, studies have not reported any serious problems or deaths.

In summary, both Peptamen 1.5 and Prosol 20% IV have undergone safety studies. Peptamen 1.5 is generally well-tolerated, while Prosol 20% IV carries some risk of allergic reactions, though serious issues are rare. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard nutritional support for critically ill patients, which often involves enteral feeding alone, researchers are excited about the potential of combining enteral nutrition with intravenous amino acid supplementation. The study treatments, Peptamen 1.5% and Prosol 20% IV, aim to enhance protein intake significantly. Group 2 seeks to achieve a protein intake of 1.75 g/kg/day, while Group 3 targets 2.5 g/kg/day through the innovative use of Prosol 20% IV. This approach could lead to more effective muscle maintenance and recovery in critically ill patients, addressing the typical shortfall in protein absorption from enteral nutrition alone.

What evidence suggests that this trial's treatments could be effective for critical illness?

Research shows that Peptamen 1.5%, administered via enteral feeding to participants in Group 1 of this trial, can improve the health of seriously ill patients. Studies have found it can lessen the severity of illness and may help patients leave the hospital sooner. Patients generally tolerate it well without worsening symptoms.

Participants in Groups 2 and 3 will receive Prosol 20% IV in addition to Peptamen 1.5%. Studies suggest that administering amino acids through an IV can lower the risk of death and improve kidney health in seriously ill patients. This approach offers hope for better survival rates and overall health. Both treatments aim to boost nutrition and recovery in very sick patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Arnold S Kristof, MDCM, FRCPC

Principal Investigator

McGill University Health Centre/Research Institute of the McGill University Health Centre

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are critically ill, on mechanical ventilation in the ICU, and expected to need intensive care for at least three more days. It's not suitable for those with conditions that might interfere with the study or pose extra risks.

Inclusion Criteria

I am an adult on a ventilator in the ICU and expected to need it or other intensive care for at least 3 more days.

Exclusion Criteria

I have a connection between my lung and chest wall.

I am not on dialysis or ECMO because they affect how my body handles proteins.

Patients who are moribund (expected death within 48 hours)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive intravenous amino acids and enteral feeding to assess protein metabolism and anabolic processes

48 hours

Continuous monitoring in ICU

Follow-up

Participants are monitored for safety, effectiveness, and secondary outcomes such as mortality and hospital-acquired infections

72 hours to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Peptamen 1.5%
• Prosol 20% IV

Trial Overview The study tests if giving extra amino acids through Peptamen (a nutrient mix) via a feeding tube or Prosol IV can help build up body proteins in critically ill patients better than standard care.

How Is the Trial Designed?

Group I: Group 2: Prosol 20% IV to 1.75g/kg/day Active Control 2 Interventions

Patients in group 2 will receive the same enteral feeding as group 1 (Peptamen 1.5) but in addition will receive sufficient intravenous amino acid supplements (Prosol 20%) to achieve an effective fixed dose of 1.75 g/kg/d

Group II: Group 3: Prosol 20% IV to 2.5g/kg/day Active Control 2 Interventions

Patients in this group will receive intravenous amino acids (Prosol 20%) in addition to standard enteral Peptamen 1.5% to achieve an effective protein intake of 2.5 g/kg/day.

Group III: Group 1: Peptamen 1.5% via enteral only Active Control 1 Intervention

Study patients in this group will be prescribed 1.0 g/kg/d of protein using standard EN Peptamen 1.5%. Based on current compliance or tolerance statistics, investigators expect patients to only receive 50-60% of these prescribed doses; effective protein intake will therefore be approximately 0.5-0.6 g/kg/d

Peptamen 1.5% is already approved in United States, European Union for the following indications:

Approved in United States as Peptamen 1.5 for:

• Malabsorption
• Short bowel syndrome
• Chronic diarrhea
• Cystic fibrosis
• Malnutrition
• Cerebral palsy
• Crohn's disease

Approved in European Union as Peptamen 1.5 for:

• Impaired GI function
• Malabsorption
• Short bowel syndrome
• Chronic diarrhea
• Cystic fibrosis
• Malnutrition
• Cerebral palsy
• Crohn's disease

Who Is Running the Clinical Trial?

Arnold Kristof

Lead Sponsor

Trials

1

Recruited

30+

Published Research Related to This Trial

In a study involving 458 hospitalized adult patients, olive-oil-based three-chamber bags (3CBs) for parenteral nutrition were found to be non-inferior to soybean-oil-based compounded bags (CoBs) in terms of efficacy, as measured by serum prealbumin levels after 5 days.

The olive-oil-based 3CBs were not only well tolerated but also associated with a significantly lower infection rate compared to the soybean-based CoBs, suggesting a potential safety advantage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition. Jia, Z., Yang, J., Qin, H.[2022]

In a study of 119 critically ill patients receiving parenteral nutrition, those given a higher amino acid intake of 1.2 g/kg showed improved handgrip strength and reduced fatigue compared to those receiving 0.8 g/kg, although grip strength at ICU discharge was not significantly different overall.

The higher amino acid intake also resulted in greater muscle thickness and better nitrogen balance early in the treatment, supporting the recommendation for increased protein provision in ICU patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protein Requirements in the Critically Ill: A Randomized Controlled Trial Using Parenteral Nutrition. Ferrie, S., Allman-Farinelli, M., Daley, M., et al.[2022]

In critically ill children requiring parenteral nutrition, soybean oil lipid injectable emulsion (SO-ILE) was linked to a higher incidence of hypertriglyceridemia (HTG) and elevated inflammatory markers compared to a mixed lipid emulsion (SO,MCT,OO,FO-ILE).

The study found that the mortality rate was significantly higher in the SO-ILE group, with an adjusted odds ratio of 2.3, indicating a potential safety concern with this lipid formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SO,MCT,OO,FO-ILE Is Associated With Better Side Effect Profile Than SO-ILE in Critically Ill Children Receiving Parenteral Nutrition. Gupta, N., Ali, C., Talathi, S.[2023]

Early enteral nutrition after major rectal surgery led to better clinical outcomes, such as reduced postoperative ileus and shorter hospital stays, compared to early parenteral nutrition in a study of 123 patients.

Despite lower plasma concentrations of glutamine and arginine in the enteral nutrition group, these amino acid levels did not explain the improved recovery outcomes, suggesting that the benefits of early enteral feeding are not directly linked to plasma amino acid levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial Effects of Early Enteral Nutrition After Major Rectal Surgery: A Possible Role for Conditionally Essential Amino Acids? Results of a Randomized Clinical Trial. van Barneveld, KW., Smeets, BJ., Heesakkers, FF., et al.[2017]

In critical illness, skeletal muscle undergoes adaptations that can lead to insulin resistance and muscle wasting, making adequate protein and amino acid nutrition essential for recovery, with optimal intake levels suggested to be between 1.3 and 1.5 g/kg/day.

Anabolic resistance in critically ill patients reduces the effectiveness of protein intake, highlighting the importance of mobility protocols in intensive care to enhance nutritional interventions and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protein metabolism and requirements. Biolo, G.[2019]

In a study of 9 critically ill children receiving continuous renal replacement therapy, the standard meropenem dosing of 40 mg/kg every 12 hours was found to achieve the desired antibiotic concentration in only 32% of cases.

Alternative dosing regimens of 20 mg/kg every 8 hours over 4 hours or 40 mg/kg every 8 hours over 2 hours successfully met the pharmacokinetic/pharmacodynamic target for 90% of patients, indicating these may be more effective dosing strategies for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal Dosing of Meropenem in a Small Cohort of Critically Ill Children Receiving Continuous Renal Replacement Therapy. Tan, WW., Watt, KM., Boakye-Agyeman, F., et al.[2023]

A review of 21 studies on beta-lactam antibiotics in septic pediatric patients highlights the importance of individualized antimicrobial therapy based on pharmacokinetic/pharmacodynamic (PK/PD) parameters to effectively treat life-threatening infections.

Strategies such as prolonging infusion times and increasing frequency of administration were commonly used to enhance the effectiveness of beta-lactams, suggesting that therapeutic monitoring could improve treatment outcomes in septic children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta-Lactams Therapeutic Monitoring in Septic Children-What Target Are We Aiming for? A Scoping Review. Morales Junior, R., Pereira, GO., Tiguman, GMB., et al.[2022]

Amino acid-based nutritional support is important for improving nitrogen balance in critically ill, catabolic patients, but the optimal composition of amino acids is still being defined.

The review highlights the significance of conditionally indispensable amino acids and suggests specific amino acids like histidine, serine, and glutamine, as well as the potential benefits of using dipeptides for parenteral nutrition in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are intravenous amino acid solutions unbalanced? Fürst, P., Stehle, P.[2005]

For adult patients receiving parenteral nutrition (PN), a general amino acid intake of 0.8 g/kg/day is recommended, which can be increased to 1.2-1.5 g/kg/day in normal conditions and up to 2.0-2.5 g/kg/day in exceptional cases, ensuring adequate protein synthesis and reduced catabolism.

In critically ill patients, glutamine should be administered parenterally if indicated, while specific amino acid solutions, such as those with branched-chain amino acids, are recommended for treating hepatic encephalopathy, but not for other conditions like acute pancreatitis or after bone marrow transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amino acids - Guidelines on Parenteral Nutrition, Chapter 4. Stein, J., Boehles, HJ., Blumenstein, I., et al.[2021]

Using an individualized pharmacokinetic algorithm for protamine dosing after cardiopulmonary bypass resulted in a significantly lower protamine requirement compared to a fixed-dose model, with patients needing an average of 243 mg versus 305 mg (p<0.001).

The algorithm did not negatively impact clotting times or transfusion requirements, suggesting it is a safe and effective alternative to traditional dosing methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot validation of an individualised pharmacokinetic algorithm for protamine dosing after systemic heparinisation for cardiopulmonary bypass. Miles, LF., Marchiori, P., Falter, F.[2018]

Two patients with advanced tumors experienced severe adverse reactions after receiving parenteral nutrition containing fat emulsion (10%)/amino acids (15)/glucose (20%), highlighting potential safety concerns with this nutritional support.

Despite the adverse reactions, symptoms were relieved upon stopping the infusion, and the patients did not experience similar side effects upon re-administration, suggesting that careful monitoring and individualized administration plans are crucial for safe use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe side effects caused by parenteral nutrition therapy with fat emulsion (10%)/amino acids (15)/glucose (20%) injection: 2 case reports. Jia, H., Sun, Y., Hou, F., et al.[2022]

Continuous infusion (CI) of beta-lactam antibiotics in critically ill children resulted in a higher likelihood of achieving optimal pharmacokinetic exposure compared to intermittent infusion (II), with 69% of CI patients meeting the target versus 47% of II patients.

While CI improved the chances of optimal exposure, it also increased the risk of overexposure, highlighting the need for regular therapeutic drug monitoring in these patients to ensure safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta-lactam exposure and safety in intermittent or continuous infusion in critically ill children: an observational monocenter study. Debray, A., Callot, D., Hirt, D., et al.[2023]

In a study of 28 critically ill children receiving continuous vancomycin infusion, the current dosing scheme was found to be inadequate, leading to underexposure in many patients, with 25% exceeding the recommended area under the curve for effective treatment.

The use of pharmacokinetic models to adjust initial dosing based on individual patient factors like age and weight could improve vancomycin therapy effectiveness, aiming for better target attainment in plasma concentrations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Achievement of Therapeutic Vancomycin Exposure With Continuous Infusion in Critically Ill Children. Genuini, M., Oualha, M., Bouazza, N., et al.[2019]

Alternative intravenous fat emulsions (IVFEs) like medium-chain triglycerides, olive oils, and fish oils may offer similar safety profiles to standard soybean oil-based IVFEs, but they are not yet available in the U.S.

These alternative IVFEs could potentially improve clinical outcomes for patients in compromised states by reducing the intake of proinflammatory ω-6 fatty acids found in soybean oil, suggesting a need for further research on their efficacy and optimal use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A.S.P.E.N. position paper: Clinical role for alternative intravenous fat emulsions. Vanek, VW., Seidner, DL., Allen, P., et al.[2015]

In a study involving 78 critically ill neonates, an olive oil-based lipid emulsion (ClinOleic) was found to be well tolerated with no adverse events, indicating its safety for use in this vulnerable population.

After 5 days of treatment, the olive oil emulsion significantly increased plasma levels of oleic acid compared to a soybean oil emulsion, while also showing a lower increase in linoleic acid, reflecting the different fatty acid compositions of the emulsions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and safety of olive oil-based lipid emulsion in critically ill neonates: a blinded randomized trial. Webb, AN., Hardy, P., Peterkin, M., et al.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8491306/

Clinical Case Reports on the acceptability and tolerance of a ... H had no worsening symptoms regarding her GORD or bowel frequency when taking the Peptamen Junior 1.5 orally or given via feeding tube. H ...

2. nestlehealthscience.com nestlehealthscience.com/sites/default/files/asset-library/documents/adult-enteral-nutrition/publications-commercial/peptamen/2016_peptamen_has_proof.pdf

PEPTAMEN® has the Proof The Peptamen group had significantly fewer stools than the free amino acid group (p<0.02). Both groups had equal tube-feeding intake. The LOS was 45 days.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5466775/

A randomized controlled pilot study to evaluate the effect of ... In this pilot study, we found a high incidence of diarrhea, which was not attenuated by Peptamen® AF. Patients with diarrhea stayed longer in the ICU.

4. nestlehealthscience.ca nestlehealthscience.ca/sites/default/files/asset-library/documents/peptamen/study-summaries-3233w5%20nhs%20peptamen%20evidence%20sales%20aid%20fa%20lr.pdf

Evidence in Support of Peptamen® Formulas Peptamen® patients had significantly greater improvement in severity of illness scores (Ranson criteria) and trend toward improvement in LOS, ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02865408?term=AREA%5BConditionSearch%5D(Critical%20Illness)%20AND%20AREA%5BInterventionSearch%5D(Amino%20Acids)&rank=1

Study Details | Amino Acid Nutrition in the Critically-ill Patients in this group will receive intravenous amino acids ( Prosol 20%) in addition to standard enteral Peptamen 1.5% to achieve an effective protein intake ...

6. nestlemedicalhub.com nestlemedicalhub.com/products/peptamen-junior-15

PEPTAMEN JUNIOR® 1.5 Specifically designed for children ages 1-13 with impaired GI function, Peptamen Junior® 1.5 is a calorically dense pediatric tube feeding formula that provides ...

7. peptamen.com peptamen.com/product/peptamen-juniorr-15

Peptamen Junior® 1.5 Product Info Peptamen Junior® 1.5 is a peptide-based and calorically dense enteral nutrition formula for children with volume restrictions or high calorie requirements.

8. nestlehealthscience.co.uk nestlehealthscience.co.uk/sites/default/files/2021-04/Peptamen%20Junior%201.5%20Data%20Card_Apr%2021.pdf

PEPTAMEN® JUNIOR 1.5 ACBS approved, prescribable on FP10 (GP10 in Scotland). Indicated as a sole source of nutrition for children aged 1-15 years for the dietary management of.

9. peptamen.com peptamen.com/product/peptamen-15

Peptamen 1.5 Nutrition Information Peptamen 1.5 is a peptide-based and calorically dense enteral nutrition formula for individuals with volume-restrictions or high-calorie needs.

10. nestlehealthscience.ca nestlehealthscience.ca/en/brands/peptamen-junior/peptamen-junior-1-5-hcp

Peptamen Junior 1.5 - Features and Ingredients Peptamen® Junior 1.5 meets the nutritional needs of children 1-13 years. It includes a peptide based, 100% whey protein and 60% MCT. Discover more here.