Clinical trial NCT05296096: PRotein Optimization With eXercise to Improve MUscle Mass and Functional outcomeS
Official title: PRotein Optimization With eXercise to Improve MUscle Mass and Functional outcomeS - a Pilot Feasibility, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Muscle Loss
Protein
Mobility
Pediatric ALL
Keywords: protein
exercise
mechanical ventilation
outcome
nutrition
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: Johns Hopkins University
First posted: 2022-03-25
Enrollment: 72
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The investigators have designed a 2-center, pilot feasibility, randomized controlled trial (PROXIMUS) to determine the feasibility and safety of a larger multi center, randomized open-label trial comparing high protein combined with individualized exercise vs. standard management during the acute phase of critical illness in children. The investigators aim to determine the impact of the intervention on preservation of muscle mass; and functional status at 1 month and 6 months after randomization.

Detailed description: Mortality in U.S. pediatric intensive care units (PICUs) is improving, resulting in an increased focus on the quality of life of survivors who often have persistent physical, cognitive, and psychological impairments. Mechanically ventilated children in particular experience immobilization and poor nutrient intake, which results in muscle loss during acute illness. Early mobility and optimal nutrition during acute critical illness have been associated with muscle mass preservation and decreased duration of mechanical ventilation. These interventions may have the potential to decrease preventable PICU-acquired morbidities. However, the optimal doses and long-term benefits of these interventions have not been shown in randomized studies of critically ill PICU patients.

Thus, the investigators will test the first pediatric-specific, inter-professional intervention that integrates high protein and individualized exercise. This intervention was developed by a team of experts in the fields of nutrition, early mobility, rehabilitative exercise, muscle ultrasound (US), and functional outcomes.

The investigators propose a 2-center, pilot feasibility, randomized controlled trial (PROXIMUS) with the following Specific Aims:

1. To determine the feasibility and safety of a randomized open-label trial comparing high protein combined with individualized exercise vs. standard management during the acute phase of critical illness in children;
2. To determine the impact of high protein and individualized exercise on preservation of muscle mass; and
3. To determine the impact of high protein and individualized exercise on functional status at 1 month and 6 months after randomization.

Outcomes: The investigators will assess feasibility with a composite measure that combines predetermined thresholds for screening, enrollment, allocation, and compliance/adherence with significant separation in doses of protein and exercise between the two arms. Safety will be defined as absence of difference in rates of new renal injury and exercise related adverse events.

Preservation of muscle mass will be assessed by percent daily change in US-measured quadriceps femoris muscle thickness (QFMT) during the PICU stay. The investigators will use a validated imaging protocol with high reliability and reproducibility. The investigators will also examine the difference in the normative standard scores (T-scores) between the two arms for the Pediatric Evaluation of Disability Inventory - Computer Adaptive Test (PEDI-CAT) assessment. Other secondary outcomes are Functional Status Scale, PedsQL, and muscle quality by US.

The investigators hypothesize that a larger trial will be feasible and safe. Patients randomized to the combined intervention will have lower decline in QFMT and better scores on PEDI-CAT assessment.

If proven feasible and safe, the PROXIMUS intervention has potential to profoundly change medical care in the PICU and substantially impact public health by improving long-term outcomes for the growing number of pediatric survivors of critical illness.

Eligibility criteria: Inclusion Criteria:

1. ICU patients aged 1 year (corrected) to \<18 years
2. Require mechanical ventilation (endotracheal intubation or tracheostomy, or initiation of noninvasive ventilation) in the first 72 hours of PICU admission.
3. Able to consent to participate within 72 hours of initiation of mechanical ventilation initiation.

Exclusion Criteria:

* Patients unable to receive EN, PN, or who are on a specialized diet incompatible with the study intervention
* Fulminant liver failure
* Kidney failure (≥KDIGO Stage 3) without replacement therapy
* Functional Status Scale score at PICU admission \<9
* End of life/redirection of care
* ECMO therapy
* Continuous neuromuscular blockade and/or bedrest is medically or surgically necessitated Participation in a conflicting interventional trial
* High risk of refeeding syndrome
* Inborn errors of metabolism
* High BSA burns.

Primary outcomes:
measure: Feasibility of recruitment and adherence to study procedures
timeFrame: Through study completion, up to 10 days
measure: Tolerability of protein intervention (serum creatinine change)
timeFrame: Through study completion, up to 10 days
measure: Safety of protein (new renal injury) and exercise interventions (any associated adverse events)
timeFrame: Through study completion, up to 10 days
Secondary outcomes:
measure: Change in Muscle mass thickness
timeFrame: Through study completion, up to 10 days
measure: Functional assessment - motor, cognitive and responsibility
timeFrame: 6 months
measure: Multidimensional Pediatric Health related Quality of Life assessment (Physical, Emotional, Social, School Functioning domains) using a validated tool
timeFrame: 6 months
measure: Assessment of Functional status - sensory, communication, motor, sensory and feeding
timeFrame: 6 months
Other outcomes:
measure: Protein catabolism (breakdown)
timeFrame: 10 days
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
Study officials:
affiliation: Faculty, Boston Children's Hospital
name: Nilesh Mehta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Faculty, Johns Hopkins
name: Sapna R Kudchadkar, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mehta NM, Bechard LJ, Cahill N, Wang M, Day A, Duggan CP, Heyland DK. Nutritional practices and their relationship to clinical outcomes in critically ill children--an international multicenter cohort study*. Crit Care Med. 2012 Jul;40(7):2204-11. doi: 10.1097/CCM.0b013e31824e18a8.
citation: Hauschild DB, Oliveira LDA, Farias MS, Barbosa E, Bresolin NL, Mehta NM, Moreno YMF. Enteral Protein Supplementation in Critically Ill Children: A Randomized Controlled Pilot and Feasibility Study. JPEN J Parenter Enteral Nutr. 2019 Feb;43(2):281-289. doi: 10.1002/jpen.1416. Epub 2018 Jun 30.
citation: Mehta NM, Bechard LJ, Zurakowski D, Duggan CP, Heyland DK. Adequate enteral protein intake is inversely associated with 60-d mortality in critically ill children: a multicenter, prospective, cohort study. Am J Clin Nutr. 2015 Jul;102(1):199-206. doi: 10.3945/ajcn.114.104893. Epub 2015 May 13.
citation: Wieczorek B, Ascenzi J, Kim Y, Lenker H, Potter C, Shata NJ, Mitchell L, Haut C, Berkowitz I, Pidcock F, Hoch J, Malamed C, Kravitz T, Kudchadkar SR. PICU Up!: Impact of a Quality Improvement Intervention to Promote Early Mobilization in Critically Ill Children. Pediatr Crit Care Med. 2016 Dec;17(12):e559-e566. doi: 10.1097/PCC.0000000000000983.
citation: Choong K, Canci F, Clark H, Hopkins RO, Kudchadkar SR, Lati J, Morrow B, Neu C, Wieczorek B, Zebuhr C. Practice Recommendations for Early Mobilization in Critically Ill Children. J Pediatr Intensive Care. 2018 Mar;7(1):14-26. doi: 10.1055/s-0037-1601424. Epub 2017 Apr 10.