PRotein Optimization With eXercise to Improve MUscle Mass and Functional outcomeS

Pediatric ALL Clinical Trial

— PROXIMUS  

Official title:

PRotein Optimization With eXercise to Improve MUscle Mass and Functional outcomeS - a Pilot Feasibility, Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05296096
• Other study ID #: P00040737
• Status: Recruiting
• Phase: N/A
• Start date: February 20, 2023
• Est. completion date: June 30, 2026

Study information

• Verified date: January 2024
• Source: Boston Children's Hospital
• Contact: Nilesh M. Mehta, MD
• Phone: 6173557327
• Email: nilesh.mehta[@]childrens.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: June 30, 2026
• Est. primary completion date: December 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Mobility
• Muscle Loss
• Pediatric ALL
• Protein

Intervention

Other:
• Protein dosage and rehabilitation team delivered exercise prescription
The dietitian and rehabilitation team will be consulted on enrollment and will assess the patient for nutritional and functional status using the institutional criteria and physical exam. The study dietitian will prescribe the protein goal based on the randomization assignment and age group. For the high protein arm, protein goals will be 3g/kg/day for ages 1-1yrs, and 2.4g/kg/day for ages greater than 12 years. The rehabilitation team will determine the appropriate highest level of mobility (HLM) for the day in collaboration with the medical team on morning rounds. The rehabilitation team will prescribe passive or active participation in two 30-minute HLM sessions, individualized to their baseline function and clinical status and/or restrictions.

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Boston Children's Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Boston Children's Hospital	Johns Hopkins University

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Protein catabolism (breakdown)	Proteomic profile measured in urine during the PICU stay	10 days
Primary	Feasibility of recruitment and adherence to study procedures	Feasibility (primary composite outcome) will be assessed by the following metrics: (1) >80% of eligible patients are approached for consent; (2) >35% of eligible patients are randomized (enrollment and consent); (3) >80% of consented patients receive study treatments (allocation and adherence).	Through study completion, up to 10 days
Primary	Tolerability of protein intervention (serum creatinine change)	Incidence of treatment-related adverse events as assessed by 3-fold rise in serum creatinine or intolerance (new emesis or diarrhea) related to the study diet.	Through study completion, up to 10 days
Primary	Safety of protein (new renal injury) and exercise interventions (any associated adverse events)	Incidence of treatment-related adverse events; specifically new renal injury or injury/discomfort associated with exercise.	Through study completion, up to 10 days
Secondary	Change in Muscle mass thickness	As assessed by the change in quadriceps femoris (QF) muscle thickness between baseline measurement and measurement on study completion.	Through study completion, up to 10 days
Secondary	Functional assessment - motor, cognitive and responsibility	The investigators will administer the Pediatric Evaluation of Disability Inventory - Computer Adaptive Test (PEDI-CAT) test at 1 and 6 months after enrollment, and compare the scaled T-scores between the two trial arms at each time point. Higher score is better.	6 months
Secondary	Multidimensional Pediatric Health related Quality of Life assessment (Physical, Emotional, Social, School Functioning domains) using a validated tool	The investigators will administer the Pediatric Health Related Quality of Life Questionnaire (PedsQoL) test at 1 and 6 months after enrollment, and compare the score between the two trial arms at each time point. Higher score on the developmentally appropriate questionnaire is better.	6 months
Secondary	Assessment of Functional status - sensory, communication, motor, sensory and feeding	The investigators will administer the Functional Status Scale (FSS) assessment at 1 and 6 months after enrollment, and compare this scale between the two trial arms at each time point. The scale ranges from 6 to 30 points, lower is better,	6 months