Nutrition and Exercise in Critical Illness

NCT03021902 | Completed Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: The NEXIS Trial
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 7

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.

Conditions

Acute Respiratory Failure

Outcome Measures

Primary Outcomes (1)

• Physical functioning

  6-minute walk distance

  Hospital discharge (up to 26 weeks after randomization)

Secondary Outcomes (34)

• Overall strength-upper extremity

  Hospital discharge (up to 26 weeks after randomization)

• Overall strength-lower extremity

  Hospital discharge (up to 26 weeks after randomization)

• Quadriceps force-lower extremity strength

  Hospital discharge (up to 26 weeks after randomization)

• Distal strength-hand grip strength

  ICU and hospital discharge (up to 26 weeks after randomization)

• Overall Physical Functional status - Short Physical Performance Battery

  ICU and hospital discharge (up to 26 weeks after randomization)

Study Arms (2)

IV amino acid + in-bed cycle ergometry

EXPERIMENTAL

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; Device: In-bed cycle ergometry exercise

Usual care

NO INTERVENTION

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

Interventions

IV amino acids 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.

Also known as: Clinisol 15% (Baxter) - sulfite-free (Amino Acid) Injection

IV amino acid + in-bed cycle ergometry

In-bed cycle ergometry exercise 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.

Also known as: MotoMed Letto II Cycle Ergometer

IV amino acid + in-bed cycle ergometry

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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).

You may not qualify if:

• \>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).
• 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

Sponsors & Collaborators

• Clinical Evaluation Research Unit at Kingston General Hospital: lead
• University of Vermont: collaborator
• Johns Hopkins University: collaborator

Study Sites (7)

University of Kentucky

Lexington, Kentucky, 40506, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Montefiore Albert Einstein College of Medicine

The Bronx, New York, 10467, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Vermont College of Medicine

Burlington, Vermont, 05405, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Related Publications (11)

• Burtin C, Clerckx B, Robbeets C, Ferdinande P, Langer D, Troosters T, Hermans G, Decramer M, Gosselink R. Early exercise in critically ill patients enhances short-term functional recovery. Crit Care Med. 2009 Sep;37(9):2499-505. doi: 10.1097/CCM.0b013e3181a38937.

  PMID: 19623052 BACKGROUND

• Chan KS, Pfoh ER, Denehy L, Elliott D, Holland AE, Dinglas VD, Needham DM. Construct validity and minimal important difference of 6-minute walk distance in survivors of acute respiratory failure. Chest. 2015 May;147(5):1316-1326. doi: 10.1378/chest.14-1808.

  PMID: 25742048 BACKGROUND

• Kho ME, Truong AD, Zanni JM, Ciesla ND, Brower RG, Palmer JB, Needham DM. Neuromuscular electrical stimulation in mechanically ventilated patients: a randomized, sham-controlled pilot trial with blinded outcome assessment. J Crit Care. 2015 Feb;30(1):32-9. doi: 10.1016/j.jcrc.2014.09.014. Epub 2014 Sep 22.

  PMID: 25307979 BACKGROUND

• Heyland D, Muscedere J, Wischmeyer PE, Cook D, Jones G, Albert M, Elke G, Berger MM, Day AG; Canadian Critical Care Trials Group. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med. 2013 Apr 18;368(16):1489-97. doi: 10.1056/NEJMoa1212722.

  PMID: 23594003 BACKGROUND

• National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Rice TW, Wheeler AP, Thompson BT, Steingrub J, Hite RD, Moss M, Morris A, Dong N, Rock P. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA. 2012 Feb 22;307(8):795-803. doi: 10.1001/jama.2012.137. Epub 2012 Feb 5.

  PMID: 22307571 BACKGROUND

• National Heart, Lung, and Blood Institute ARDS Clinical Trials Network; Truwit JD, Bernard GR, Steingrub J, Matthay MA, Liu KD, Albertson TE, Brower RG, Shanholtz C, Rock P, Douglas IS, deBoisblanc BP, Hough CL, Hite RD, Thompson BT. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med. 2014 Jun 5;370(23):2191-200. doi: 10.1056/NEJMoa1401520. Epub 2014 May 18.

  PMID: 24835849 BACKGROUND

• Parry SM, Berney S, Koopman R, Bryant A, El-Ansary D, Puthucheary Z, Hart N, Warrillow S, Denehy L. Early rehabilitation in critical care (eRiCC): functional electrical stimulation with cycling protocol for a randomised controlled trial. BMJ Open. 2012 Sep 13;2(5):e001891. doi: 10.1136/bmjopen-2012-001891. Print 2012.

  PMID: 22983782 BACKGROUND

• Fan E, Zanni JM, Dennison CR, Lepre SJ, Needham DM. Critical illness neuromyopathy and muscle weakness in patients in the intensive care unit. AACN Adv Crit Care. 2009 Jul-Sep;20(3):243-53. doi: 10.1097/NCI.0b013e3181ac2551.

  PMID: 19638746 BACKGROUND

• Dowdy DW, Dinglas V, Mendez-Tellez PA, Bienvenu OJ, Sevransky J, Dennison CR, Shanholtz C, Needham DM. Intensive care unit hypoglycemia predicts depression during early recovery from acute lung injury. Crit Care Med. 2008 Oct;36(10):2726-33. doi: 10.1097/CCM.0b013e31818781f5.

  PMID: 18766087 BACKGROUND

• Al-Dorzi HM, Stapleton RD, Arabi YM. Nutrition priorities in obese critically ill patients. Curr Opin Clin Nutr Metab Care. 2022 Mar 1;25(2):99-109. doi: 10.1097/MCO.0000000000000803.

  PMID: 34930871 DERIVED

• Heyland DK, Day A, Clarke GJ, Hough CT, Files DC, Mourtzakis M, Deutz N, Needham DM, Stapleton R. Nutrition and Exercise in Critical Illness Trial (NEXIS Trial): a protocol of a multicentred, randomised controlled trial of combined cycle ergometry and amino acid supplementation commenced early during critical illness. BMJ Open. 2019 Jul 31;9(7):e027893. doi: 10.1136/bmjopen-2018-027893.

  PMID: 31371287 DERIVED

MeSH Terms

Interventions

Amino Acids; Injections

Intervention Hierarchy (Ancestors)

Amino Acids, Peptides, and Proteins; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: December 21, 2016
• First Posted: January 16, 2017
• Study Start: September 28, 2017
• Primary Completion: January 14, 2025
• Study Completion: June 23, 2025
• Last Updated: August 27, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)