Nutrition and Exercise in Critical Illness (NEXIS)
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ClinicalTrials.gov Identifier: NCT03021902 |
Recruitment Status :
Recruiting
First Posted : January 16, 2017
Last Update Posted : September 5, 2021
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Condition or disease | Intervention/treatment | Phase |
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Acute Respiratory Failure | Drug: IV amino acids Device: In-bed cycle ergometry exercise | Phase 2 |

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 |

Arm | Intervention/treatment |
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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
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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.
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- Physical functioning [ Time Frame: Hospital discharge (up to 26 weeks after randomization) ]6-minute walk distance
- Overall strength-upper extremity [ Time Frame: Hospital discharge (up to 26 weeks after randomization) ]MRC Sum-score (Medical Research Council (MRC) Scale for Muscle Strength). Subscales scored 0-5, where 5 is normal. Total score is the sum of the 6 upper extremity subscales.
- Overall strength-lower extremity [ Time Frame: Hospital discharge (up to 26 weeks after randomization) ]MRC Sum-score (Medical Research Council (MRC) Scale for Muscle Strength). Subscales scored 0-5, where 5 is normal. Total score is the sum of the 6 lower extremity subscales.
- 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 5 items are performed: rolling, transfer from supine to sit, sitting at the edge of bed, transfer from sit to stand, and walking Each task is evaluated using an eight-point ordinal scale ranging from 0 (unable to perform) to 7 (complete independence) Item scores are summed The total score ranges from 0-35, with higher scores indicating better physical functioning.
- 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) All items are scored so that a high score defines a more favorable health state.
Each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100 Items in the same scale are averaged together to create the 8 scale scores. Items that are left blank (missing data) are not taken into account when calculating the scale scores.
Scale scores represent the average for all items in the scale that the respondent answered.
- 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) Total score where 6 = High (patient independent) 0 = Low (patient very dependent)
- Physical functioning - Lawton IADL [ Time Frame: Telephone survey at 6 months ]Lawton Instrument Activities of Daily Living Scale (Lawton IADL) A summary score ranges from 0 (low function, dependent) to 8 (high function, independent) for women and 0 through 5 for men to avoid potential gender bias.
- 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 The total possible score is 22 points; a score of 18 or above is considered normal
- Mental and Cognitive Functioning - HADS [ Time Frame: Telephone survey at 6 months ]Hospital Anxiety and Depression Scale The HADS questionnaire has seven items each for depression and anxiety subscales. Scoring for each item ranges from zero to three, with three denoting highest anxiety or depression level. A total subscale score of >8 points out of a possible 21 denotes considerable symptoms of anxiety or depression.
- Mental and Cognitive Functioning - IES-R [ Time Frame: Telephone survey at 6 months ]Impact of Events Scale Scoring for each item ranges from 0-4 Total score ranges from 0-88, where a total score of 33 or over signifies the likely presence of PTSD
- Health Care Resource Utilization [ Time Frame: Telephone survey at 6 months ]Admission to ICU, hospital, rehabilitation & nursing facility
- Body composition - DEXA Scan [ Time Frame: At Hospital Discharge ]Whole Body DEXA Scan
- Body Composition - Heavy water [ Time Frame: Enrollment, Days 1-7 ]Fat-free and fat mass can be measured with D2O in body fluids using gas chromatography-tandem mass spectrometry.
- Plasma and muscle protein synthesis - Heavy water [ Time Frame: Enrollment, Days 1-7 ]Muscle protein synthesis will be analyzed with chromatography and mass spectrometry techniques.
- 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
- NEXIS FLAME - Lung Inflammation [ Time Frame: Enrollment, Day 5 ]Bronchoalveolar lavage neutrophil counts, IL-17A, CXCL5, and protein
- 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)
- NEXIS FLAME - Muscle inflammation [ Time Frame: Enrollment, Day 5 ]Muscle macrophages (CD45+, CD206+)

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.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- ≥18 years old.
- Requiring mechanical ventilation with actual or expected total duration of mechanical ventilation ≥ 48 hours.
- Expected ICU stay ≥ 4 days after enrollment (to permit adequate exposure to the proposed intervention).
Exclusion Criteria:
- >96 continuous hours of mechanical ventilation before enrollment.
- Expected death or withdrawal of life-sustaining treatments within this hospitalization.
- No expectation for any nutritional intake within the subsequent 72 hours.
- Severe chronic liver disease (MELD score ≥20) or acute fulminant hepatitis.
- Documented allergy to the amino acid intervention.
- Metabolic disorders involving impaired nitrogen utilization
- Not ambulating independently prior to illness that lead to ICU admission (use of gait aid permitted).
- Pre-existing primary systemic neuromuscular disease (e.g. Guillain Barre).
- Neuromuscular blocker infusion (eligible once infusion discontinued if other inclusion criteria met).
- Intracranial or spinal process affecting motor function
- Pre-existing cognitive impairment or language barrier that prohibits outcomes assessment.
- Patients in hospital >5 days prior to ICU admission
- Lower extremity impairments that prevent cycling (e.g. amputation, knee/hip injury).
- Remaining intubated for airway protection only
- Weight ≥150kg
- Physician declines patient enrollment
- Insufficient IV access
- Pregnant
- Incarcerated

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
Contact: Daren K Heyland, MD, MSc | 403-915-5573 | dkh2@queensu.ca | |
Contact: Shawna Froese | Shawna.Froese@queensu.ca |
United States, Kentucky | |
University of Kentucky | Recruiting |
Lexington, Kentucky, United States, 40506 | |
Contact: Kirby P Mayer, DPT, PhD kpmaye2@uky.edu | |
Contact: Peter Morris, MD peter.morris@uky.edu | |
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, Oregon | |
Oregon Health & Science University | Recruiting |
Portland, Oregon, United States, 97239 | |
Contact: Olivia Krol krolo@ohsu.edu | |
Contact: Akram Khan, MD khana@ohsu.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 | Terminated |
Seattle, Washington, United States, 98104 |
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 automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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: | September 5, 2021 |
Last Verified: | August 2021 |
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 |
Product Manufactured in and Exported from the U.S.: | No |
Respiratory Insufficiency Critical Illness Respiration Disorders |
Respiratory Tract Diseases Disease Attributes Pathologic Processes |