PRotein Optimization With eXercise to Improve MUscle Mass and Functional outcomeS

NCT05296096 | Recruiting DMC

• 1 other identifier: P00040737
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 2

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.

Conditions

Muscle Loss; Protein; Mobility; Pediatric ALL

Keywords

protein; exercise; mechanical ventilation; outcome; nutrition

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (4)

• Change in Muscle mass thickness

  Through study completion, up to 10 days

• Functional assessment - motor, cognitive and responsibility

  6 months

• Multidimensional Pediatric Health related Quality of Life assessment (Physical, Emotional, Social, School Functioning domains) using a validated tool

  6 months

• Assessment of Functional status - sensory, communication, motor, sensory and feeding

  6 months

Other Outcomes (1)

• Protein catabolism (breakdown)

  10 days

Study Arms (2)

Standard protein and exercise

ACTIVE COMPARATOR

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

High protein plus exercise

EXPERIMENTAL

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

Interventions

Protein dosage and rehabilitation team delivered exercise prescription OTHER

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.

High protein plus exercise; Standard protein and exercise

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Boston Children's Hospital: lead
• Johns Hopkins University: collaborator

Study Sites (2)

Johns Hopkins Hospital

Baltimore, Maryland, 21218, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Related Publications (5)

• 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.

  PMID: 22564954 BACKGROUND

• 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.

  PMID: 29959852 BACKGROUND

• 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.

  PMID: 25971721 BACKGROUND

• 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.

  PMID: 27759596 BACKGROUND

• 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.

  PMID: 31073462 BACKGROUND

MeSH Terms

Conditions

Muscular Atrophy; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Motor Activity

Condition Hierarchy (Ancestors)

Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Behavior

Study Officials

• Nilesh Mehta, MD

  Faculty, Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

• Sapna R Kudchadkar, MD, PhD

  Faculty, Johns Hopkins

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nilesh M. Mehta, MD

CONTACT

6173557327; nilesh.mehta@childrens.harvard.edu

Lori Bechard, RD, PhD

CONTACT

6173557327; lori.bechard@childrens.harvard.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Faculty, Critical Care; Professor of Anesthesia

Study Record Dates

• First Submitted: March 8, 2022
• First Posted: March 25, 2022
• Study Start: February 20, 2023
• Primary Completion: December 1, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: January 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)