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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05296096
Recruitment Status : Recruiting
First Posted : March 25, 2022
Last Update Posted : May 17, 2023
Sponsor:
Collaborator:
Johns Hopkins University
Information provided by (Responsible Party):
Nilesh M. Mehta, Boston Children's Hospital

Study Description
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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.

Condition or disease Intervention/treatment Phase
Muscle Loss Protein Mobility Pediatric ALL Other: Protein dosage and rehabilitation team delivered exercise prescription Not Applicable

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: PRotein Optimization With eXercise to Improve MUscle Mass and Functional outcomeS - a Pilot Feasibility, Randomized Controlled Trial
Actual Study Start Date : February 20, 2023
Estimated Primary Completion Date : March 31, 2025
Estimated Study Completion Date : July 1, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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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.


Outcome Measures
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Primary Outcome Measures :
  1. 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).

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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,


Other Outcome Measures:
  1. Protein catabolism (breakdown) [ Time Frame: 10 days ]
    Proteomic profile measured in urine during the PICU stay


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • PICU patients aged 1 year (corrected) to <18 years
  • Require mechanical ventilation (endotracheal intubation or tracheostomy) in the first 48 hours of PICU admission, and are expected to remain intubated for ≥48 hours
  • Able to consent to participate within 48 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05296096


Contacts
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Contact: Nilesh M. Mehta, MD 6173557327 nilesh.mehta@childrens.harvard.edu
Contact: Lori Bechard, RD, PhD 6173557327 lori.bechard@childrens.harvard.edu

Locations
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United States, Maryland
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21218
Contact: Sapna Kudchadkar, MD, PhD       sapna@jhmi.edu   
Principal Investigator: Sapna R Kudchadkar, MD, PhD         
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Lori Bechard, RD, PhD    617-355-7327    lori.bechard@childrens.harvard.edu   
Principal Investigator: Nilesh Mehta, MD         
Sponsors and Collaborators
Boston Children's Hospital
Johns Hopkins University
Investigators
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Principal Investigator: Nilesh Mehta, MD Faculty, Boston Children's Hospital
Principal Investigator: Sapna R Kudchadkar, MD, PhD Faculty, Johns Hopkins
More Information
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Publications:

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Responsible Party: Nilesh M. Mehta, Faculty, Critical Care; Professor of Anesthesia, Boston Children's Hospital
ClinicalTrials.gov Identifier: NCT05296096    
Other Study ID Numbers: P00040737
First Posted: March 25, 2022    Key Record Dates
Last Update Posted: May 17, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nilesh M. Mehta, Boston Children's Hospital:
protein
exercise
mechanical ventilation
outcome
nutrition