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Nutrition and Exercise in Critical Illness (NEXIS)

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: NCT03021902
Recruitment Status : Recruiting
First Posted : January 16, 2017
Last Update Posted : February 11, 2019
Sponsor:
Collaborators:
University of Vermont
Johns Hopkins University
Information provided by (Responsible Party):
Daren K. Heyland, Clinical Evaluation Research Unit at Kingston General Hospital

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.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 142 participants
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
Actual Study Start Date : September 28, 2017
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.



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


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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

  17. 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

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

  19. 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)

  20. 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)

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

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

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

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

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

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

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

  28. Body composition - DEXA Scan [ Time Frame: Hospital Discharge ]
    Whole Body DEXA Scan

  29. Body Composition - Heavy water [ Time Frame: Enrolllment, During ICU stay ]
    Fat-free and fat mass can be measured with D2O in body fluids using gas chromatography-tandem mass spectrometry.

  30. Plasma and muscle protein synthesis - Heavy water [ Time Frame: Enrolllment, During ICU stay ]
    Muscle protein synthesis will be analyzed with chromatography and mass spectrometry techniques.

  31. NEXIS FLAME - Circulating inflammatory mediators [ Time Frame: Enrollment, Days 3,5,and 8 ]
    Blood IL-17, IL-23, IL-6, TNFα, CXCK1, CXCL5, CXCL8, CCL2, SP-D, KL-6, vWF, and leukocyte counts with differential

  32. NEXIS FLAME - Lung Inflammation [ Time Frame: Enrollment, Day 5 ]
    Bronchoalveolar lavage neutrophil counts, IL-17A, CXCL5, and protein

  33. NEXIS FLAME - Muscle area [ Time Frame: Enrollment, Day 5 ]
    Single muscle fiber cross-sectional area (CSA), UPS expression, MuRF1 expression, myosin protein content (all from vastus lateralis sampling)

  34. NEXIS FLAME - Muscle inflammation [ Time Frame: Enrollment, Day 5 ]
    Muscle macrophages (CD45+, CD206+)



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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

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): NCT03021902


Contacts
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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
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United States, Maryland
Johns Hopkins Hospital 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 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 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 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
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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
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Daren K. Heyland, Director, Clinical Evaluation Research Unit at Kingston General Hospital
ClinicalTrials.gov Identifier: NCT03021902    
Other Study ID Numbers: The NEXIS Trial
First Posted: January 16, 2017    Key Record Dates
Last Update Posted: February 11, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to share IPD.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Respiratory Insufficiency
Critical Illness
Respiration Disorders
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes