PRotein Optimization With eXercise to Improve MUscle Mass and Functional outcomeS (PROXIMUS)

May 27, 2026 updated by: Nilesh M. Mehta, Boston Children's Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21218
        • Johns Hopkins Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 17 years (Child)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard protein and exercise
All enrolled patients randomized to this arm will receive a baseline nutrition and nurse-driven mobility pathway and other evidence-based bundled strategies as standard of care.
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.
Experimental: High protein plus exercise

High protein nutrition: To achieve the prescribed age-appropriate high protein target, dietitians will use EN preferentially, or if EN is contraindicated, PN may be used. High-protein EN formulas and/or protein supplements (powder or liquid) will be added to formula/breast milk feedings or administered separately in divided bolus doses. Dietitians routinely employ and customize these solutions in their scope of practice. When EN is insufficient to meet protein targets, PN may be prescribed to make up the deficit on or after the end of PICU day 3. Energy and protein delivery adequacy (% of prescribed goal) will be monitored daily by the study team.

Patients in this arm will also be prescribed the age-appropriate highest-level of mobility by the rehabilitation team with a goal of 30 minutes duration, twice daily.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility of recruitment and adherence to study procedures
Time Frame: Through study completion, up to 10 days
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
Tolerability of protein intervention (serum creatinine change)
Time Frame: Through study completion, up to 10 days
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
Safety of protein (new renal injury) and exercise interventions (any associated adverse events)
Time Frame: Through study completion, up to 10 days
Incidence of treatment-related adverse events; specifically new renal injury or injury/discomfort associated with exercise.
Through study completion, up to 10 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Muscle mass thickness
Time Frame: Through study completion, up to 10 days
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
Functional assessment - motor, cognitive and responsibility
Time Frame: 6 months
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
Multidimensional Pediatric Health related Quality of Life assessment (Physical, Emotional, Social, School Functioning domains) using a validated tool
Time Frame: 6 months
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
Assessment of Functional status - sensory, communication, motor, sensory and feeding
Time Frame: 6 months
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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Protein catabolism (breakdown)
Time Frame: 10 days
Proteomic profile measured in urine during the PICU stay
10 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boston Children's Hospital

Collaborators

Johns Hopkins University

Investigators

  • Principal Investigator: Nilesh Mehta, MD, Faculty, Boston Children's Hospital
  • Principal Investigator: Sapna R Kudchadkar, MD, PhD, Faculty, Johns Hopkins

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 20, 2023

Primary Completion (Actual)

December 1, 2025

Study Completion (Actual)

January 1, 2026

Study Registration Dates

First Submitted

March 8, 2022

First Submitted That Met QC Criteria

March 15, 2022

First Posted (Actual)

March 25, 2022

Study Record Updates

Last Update Posted (Actual)

May 29, 2026

Last Update Submitted That Met QC Criteria

May 27, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P00040737

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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