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Nutrition and Exercise in Critical Illness (NEXIS)

This study is not yet open for participant recruitment.
See Contacts and Locations
Verified August 2017 by Daren K. Heyland, Clinical Evaluation Research Unit at Kingston General Hospital
Sponsor:
Collaborators:
University of Vermont
Johns Hopkins University
Information provided by (Responsible Party):
Daren K. Heyland, Clinical Evaluation Research Unit at Kingston General Hospital
ClinicalTrials.gov Identifier:
NCT03021902
First received: December 21, 2016
Last updated: August 10, 2017
Last verified: August 2017
  Purpose
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.

Condition Intervention Phase
Acute Respiratory Failure Drug: IV amino acids Device: In-bed cycle ergometry exercise Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Nutrition and Exercise in Critical Illness (The NEXIS Trial): A Randomized Trial of Combined Cycle Ergometry and Amino Acids in the ICU

Resource links provided by NLM:


Further study details as provided by Daren K. Heyland, Clinical Evaluation Research Unit at Kingston General Hospital:

Primary Outcome Measures:
  • Physical functioning [ Time Frame: Hospital discharge (up to 26 weeks after randomization) ]
    6-minute walk distance


Secondary Outcome Measures:
  • Overall strength-upper extremity [ Time Frame: Hospital discharge (up to 26 weeks after randomization) ]
    MRC Sum-score

  • Overall strength-lower extremity [ Time Frame: Hospital discharge (up to 26 weeks after randomization) ]
    MRC Sum-score

  • Quadriceps force-lower extremity strength [ Time Frame: Hospital discharge (up to 26 weeks after randomization) ]
    Hand held dynamometry

  • Distal strength-hand grip strength [ Time Frame: ICU and hospital discharge (up to 26 weeks after randomization) ]
    Hand held dynamometry

  • Overall Physical Functional status - Short Physical Performance Battery [ Time Frame: ICU and hospital discharge (up to 26 weeks after randomization) ]
    Short Physical Performance Battery

  • Overall Physical Functional status - Functional Status Score - ICU [ Time Frame: ICU and hospital discharge (up to 26 weeks after randomization) ]
    Functional Status Score - ICU

  • Mortality [ Time Frame: ICU and hospital discharge (up to 26 weeks after randomization) ]
    Chart review

  • Length of ventilation [ Time Frame: ICU and hospital discharge (up to 26 weeks after randomization) ]
    Chart review

  • ICU stay [ Time Frame: ICU and hospital discharge (up to 26 weeks after randomization) ]
    Chart review

  • Hospital stay [ Time Frame: ICU and hospital discharge (up to 26 weeks after randomization) ]
    Chart review

  • ICU readmission [ Time Frame: Hospital discharge (up to 26 weeks after randomization) ]
    Chart review

  • Re-intubation [ Time Frame: Hospital discharge (up to 26 weeks after randomization) ]
    Chart review

  • Hospital-acquired infections [ Time Frame: Hospital discharge (up to 26 weeks after randomization) ]
    Chart review

  • Discharge location (e.g. home vs. rehab) [ Time Frame: Hospital discharge (up to 26 weeks after randomization) ]
    Chart review

  • Body composition - Ultrasound [ Time Frame: Enrollment, hospital discharge, & ICU discharge (up to 26 weeks after randomization) ]
    Ultrasound of quadriceps

  • Body composition - CT - Chest when clinically available [ Time Frame: Enrollment, hospital discharge, & ICU discharge (up to 26 weeks after randomization) ]
    Chest CT

  • Body composition - CT - Abdominal Scan when clinically available [ Time Frame: Enrollment, hospital discharge, & ICU discharge (up to 26 weeks after randomization) ]
    Abdominal CT scan at 3rd lumbar vertebra

  • Health-related quality of life - SF-36 [ Time Frame: Telephone survey at 6 months ]
    36-Item Short Form Health Survey (SF-36)

  • Health-related quality of life - EQ-5D-5L [ Time Frame: Telephone survey at 6 months ]
    EuroQol Group standardized measure of health status (EQ-5D-5L)

  • Physical functioning - Katz ADL [ Time Frame: Hospital discharge (proxy) and telephone survey at 6 months ]
    Katz Index of Independence in Activities of Daily Living (Katz ADL)

  • Physical functioning - Lawton IADL [ Time Frame: Telephone survey at 6 months ]
    Lawton Instrument Activities of Daily Living Scale (Lawton IADL)

  • Physical functioning/participation - return to work [ Time Frame: Telephone survey at 6 months ]
    Return to baseline work/activity

  • Physical functioning/participation - living location [ Time Frame: Telephone survey at 6 months ]
    Living location

  • Mental and Cognitive Functioning - MoCA-BLIND [ Time Frame: Telephone survey at 6 months ]
    MoCA-BLIND

  • Mental and Cognitive Functioning - HADS [ Time Frame: Telephone survey at 6 months ]
    Hospital Anxiety and Depression Scale

  • Mental and Cognitive Functioning - IES-R [ Time Frame: Telephone survey at 6 months ]
    Impact of Events Scale

  • Health Care Resource Utilization [ Time Frame: Telephone survey at 6 months ]
    Admission to ICU, hospital, rehabilitation & nursing facility


Estimated Enrollment: 142
Anticipated Study Start Date: September 2017
Estimated Study Completion Date: March 2022
Estimated Primary Completion Date: March 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: 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.
Other Name: Clinisol 15% (Baxter) - sulfite-free (Amino Acid) Injection
Device: 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.

Other Name: MotoMed Letto II Cycle Ergometer
No Intervention: Usual care
Participants randomized to the usual care arm will receive usual care protein and exercise.

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 inhospital 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, 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).
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

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).
  9. Neuromuscular blocker infusion (eligible once infusion discontinued if other inclusion criteria met).
  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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03021902

Contacts
Contact: Daren K Heyland, MD, MSc 613-548-3232 ext 4847 dkh2@queensu.ca
Contact: John Clarke, MSc 613-549-6666 ext 4847 clarkej1@kgh.kari.net

Locations
United States, Maryland
Johns Hopkins Hospital Not yet recruiting
Baltimore, Maryland, United States, 21287
Contact: Dale M Needham, MD, PhD    410-955-3467    dale.needham@jhmi.edu   
United States, North Carolina
Wake Forest University Baptist Medical Center Not yet recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Lori Flores    336-713-0008    lflores@wakehealth.edu   
Contact: Daniel C Files, MD    336-716-2011    dfiles@wakehealth.edu   
United States, Vermont
University of Vermont College of Medicine Not yet recruiting
Burlington, Vermont, United States, 05405
Contact: Sara S Ardren, PA    802-656-7953    sara.ardren@uvmhealth.org   
Contact: Renee D Stapleton, MD, PhD    802-656-7975    renee.stapleton@uvm.edu   
United States, Washington
Harborview Medical Center Not yet recruiting
Seattle, Washington, United States, 98104
Contact: Stephanie Gundel    206-744-4523    sgundel@uw.edu   
Contact: Catherine L Hough, MD, MSc    206-744-4523    cterrlee@u.washington.edu   
Sponsors and Collaborators
Clinical Evaluation Research Unit at Kingston General Hospital
University of Vermont
Johns Hopkins University
Investigators
Principal Investigator: Daren K Heyland, MD, MSc Queen's University
Principal Investigator: Renee D Stapleton, MD, PhD University of Vermont
Principal Investigator: Dale M Needham, MD, PhD Johns Hopkins University
  More Information

Publications:

Responsible Party: Daren K. Heyland, Director, Clinical Evaluation Research Unit at Kingston General Hospital
ClinicalTrials.gov Identifier: NCT03021902     History of Changes
Other Study ID Numbers: The NEXIS Trial
Study First Received: December 21, 2016
Last Updated: August 10, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to share IPD.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Respiratory Insufficiency
Critical Illness
Respiratory Distress Syndrome, Adult
Respiration Disorders
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Lung Diseases

ClinicalTrials.gov processed this record on September 21, 2017