Nutrition and Exercise in Critical Illness

NCT ID: NCT03021902

Last Updated: 2025-08-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 115 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-28
• Study Completion Date: 2025-06-23

Brief Summary

This study proposes a novel early intervention combining Intravenous (IV) amino acids plus in-bed cycle ergometry exercise to improve physical outcomes in critically ill patients. The investigators hypothesize that this innovative approach will improve short-term physical functioning outcomes (primary outcome), as well as amino acid metabolism, body composition, and patient-reported outcomes at 6-month follow-up.

Detailed Description

The evaluation of a combination of exercise and protein supplementation in intensive care unit (ICU) patients is novel and potentially very important. For instance, outside of the ICU, in other clinical conditions, the combination of protein supplementation and exercise improves protein synthesis, muscle mass, and muscle strength compared to protein or exercise alone.[63-70] Hence, an opportunity exists to improve ICU patients' physical outcomes via evaluating the combination of optimized protein intake and early exercise in the ICU setting.

The proposed intervention and hypothesis: The investigators propose a multi-centered Phase II RCT, with blinded outcomes assessment, of a combination of intravenous (IV) amino acid supplementation and early in-bed cycle ergometry exercise versus usual care in ICU patients requiring mechanical ventilation. The investigators hypothesize that this novel combined intervention will: (1) improve physical functioning at hospital discharge; (2) reduce muscle wasting with improved amino acid metabolism and protein synthesis in-hospital; and (3) improve health-related quality of life, physical functioning, and healthcare resource utilization at 6 months after enrollment. Preliminary data show feasibility and safety of IV amino acids and the proposed exercise intervention. The investigators have chosen a primary outcome that correlates well with long-term outcomes including mortality, hospitalization, and quality of life. [54] If this Phase II trial is positive, investigators will seek funding for a Phase III RCT to demonstrate sustained improvements with a longer-term patient-centered primary outcome and to examine the feasibility, and facilitators/barriers of delivery of this intervention by ICU nurses, physical therapists, and others. If proven effective, this combined intervention has potential to revolutionize care of ICU patients and have a major public health impact on the growing number of ICU survivors.

Objectives: To demonstrate that the innovative combination of amino acid supplementation plus early in-bed cycle ergometry exercise improves physical outcomes of ICU patients.

Specific Aims of Full Phase II RCT:

1. Short-term performance-based physical function outcomes. To determine if a combined IV amino acid supplementation and in-bed cycle ergometry exercise intervention, compared to usual care, improves in hospital muscle strength and performance-based physical functioning outcomes in critically ill patients, using a primary endpoint of six-minute walk distance (6MWD) at hospital discharge.

2. Body composition. To determine if the combined intervention, compared to usual care, improves amino acid utilization and decreases muscle wasting in ICU patients (secondary endpoints).

3. Patient-reported outcomes and health care utilization at 6 months. To determine if the combined intervention, compared to usual care, improves physical functioning, health-related quality of life, and healthcare utilization at 6 months after study enrollment (secondary endpoints).

NEXIS Flame mechanisitic Ancillary sub study:

In the proposed sub-study, the addition of bronchoaveloar lavages, blood sampling and muscle sampling measures during the participant's ICU stay will provide the ability to examine the effects of the NEXIS intervention on inflammation as a possible mechanism for improved muscle weakness.

Specific Aims of the NEXIS FLAME mechanistic ancillary study:

1. To determine if the NEXIS intervention attenuates the release of IL-17 and related cytokines to reduce systemic inflammation in humans.

2. To determine if the NEXIS intervention reduces lung injury and neutrophilic lung inflammation in humans.

3. To determine if the NEXIS intervention attenuates skeletal muscle fiber atrophy via down regulation of muscle proteolytic pathways.

4. To determine if the NEXIS intervention, and exercise specifically, reduces the content of inflammatory cells in skeletal muscle.

Conditions

Acute Respiratory Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

IV amino acid + in-bed cycle ergometry

Beginning within 96 hours of initiation of mechanical ventilation, participants will receive the combined intervention that includes IV amino acids supplementation and in-bed cycle ergometry exercise

Group Type: EXPERIMENTAL

IV amino acids

Intervention Type: DRUG

IV amino acids delivered by continuous infusion, such that the total enteral and IV protein will be between 2.0-2.5 g/kg/day as a combination of amino acid infusion plus standard feeding.

In-bed cycle ergometry exercise

Intervention Type: DEVICE

In-bed cycle ergometry exercise delivered in 45-minute sessions once-daily 5 days per week according to a detailed specific protocol that includes a safety check in combination with vigorous verbal encouragement from trained research staff delivering the intervention to promote active cycling.

Cycling is protocolized to provide graduated increases in resistance during each session and between daily sessions. Cycling will continue through ICU discharge or 21 calendar days after randomization. The intervention will specifically occur during ICU stay.

Usual care

Participants randomized to the usual care arm will receive usual care protein and exercise.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

IV amino acids

IV amino acids delivered by continuous infusion, such that the total enteral and IV protein will be between 2.0-2.5 g/kg/day as a combination of amino acid infusion plus standard feeding.

Intervention Type: DRUG

In-bed cycle ergometry exercise

In-bed cycle ergometry exercise delivered in 45-minute sessions once-daily 5 days per week according to a detailed specific protocol that includes a safety check in combination with vigorous verbal encouragement from trained research staff delivering the intervention to promote active cycling.

Cycling is protocolized to provide graduated increases in resistance during each session and between daily sessions. Cycling will continue through ICU discharge or 21 calendar days after randomization. The intervention will specifically occur during ICU stay.

Intervention Type: DEVICE

Other Intervention Names

Clinisol 15% (Baxter) - sulfite-free (Amino Acid) Injection; MotoMed Letto II Cycle Ergometer

Eligibility Criteria

Inclusion Criteria

1. ≥18 years old.

2. Requiring mechanical ventilation with actual or expected total duration of mechanical ventilation ≥ 48 hours.

3. Expected ICU stay ≥ 4 days after enrollment (to permit adequate exposure to the proposed intervention).

10. Intracranial or spinal process affecting motor function

11. Pre-existing cognitive impairment or language barrier that prohibits outcomes assessment.

12. Patients in hospital >5 days prior to ICU admission

13. Lower extremity impairments that prevent cycling (e.g. amputation, knee/hip injury).

14. Remaining intubated for airway protection only

15. Weight ≥150kg

16. Physician declines patient enrollment

17. Insufficient IV access

18. Pregnant

19. Incarcerated

20. Patients with acute kidney injury (AKI) as defined by meeting any of the KDIGO criteria (below) and not receiving renal replacement therapy:

1. Increase in serum creatinine by ≥ 0.3 mg/dl within 48 hours or

2. Increase in serum creatinine to ≥ 1.5 times baseline** or

3. Urine volume <0.5 ml/kg/h for 6 hoursⴕ

Exclusion Criteria

1. >96 continuous hours of mechanical ventilation before enrollment.

2. Expected death or withdrawal of life-sustaining treatments within this hospitalization.

3. No expectation for any nutritional intake within the subsequent 72 hours.

4. Severe chronic liver disease (MELD score ≥20) or acute fulminant hepatitis.

5. Documented allergy to the amino acid intervention.

6. Metabolic disorders involving impaired nitrogen utilization

7. Not ambulating independently prior to illness that lead to ICU admission (use of gait aid permitted).

8. Pre-existing primary systemic neuromuscular disease (e.g. Guillain Barre).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Vermont

OTHER

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: collaborator

Clinical Evaluation Research Unit at Kingston General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Daren K. Heyland

Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daren K Heyland, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Queen's University

Renee D Stapleton, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Vermont

Dale M Needham, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

University of Kentucky

Lexington, Kentucky, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

Montefiore Albert Einstein College of Medicine

The Bronx, New York, United States

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States

Oregon Health & Science University

Portland, Oregon, United States

University of Vermont College of Medicine

Burlington, Vermont, United States

Harborview Medical Center

Seattle, Washington, United States

Countries

United States

References

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Reference Type: BACKGROUND

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Reference Type: DERIVED

PMID: 31371287 (View on PubMed)

Other Identifiers

The NEXIS Trial

Identifier Type: -

Identifier Source: org_study_id