Investigating the Anabolic Response to Resistance Exercise During Critical Illness

NCT05197231 | Suspended

• 1 other identifier: K 2021-10530
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

ICU patients often suffer from rapid and severe muscle loss. It is not known if physical therapy can mitigate the muscle wasting associated with critical illness. The aim of this study is to investigate the effects of resistance exercise on muscle protein turnover in ICU patients. The investigators hypothesize that resistance exercise, in addition to amino acid supplementation and routine physiotherapy, results in an improved lower limb muscle protein balance compared to amino acid supplementation and routine physiotherapy alone.

Conditions

Critical Illness; Muscle Loss

Keywords

Physiotherapy; Resistance exercise; Amino acids; Muscle protein balance

Outcome Measures

Primary Outcomes (1)

• Between-group difference in change in lower limb protein balance

  The difference between the experimental and active comparator group in change in lower limb protein balance (nmol Phenylalanine/min) from baseline to post-physiotherapy. Blood samples and lower limb blood flow measurements to determine protein kinetics are performed at baseline (before IV amino acids and physiotherapy) and at 30, 60, and 90 minutes during bed rest after the physiotherapy session.

  Time = 165-180 minutes from start of study protocol to approximate Time = 315 minutes from start of study protocol.

Secondary Outcomes (11)

• Between-group difference in change in lower limb protein synthesis

  Time = 165-180 minutes from start of study protocol to approximate Time = 315 minutes from start of study protocol.

• Between-group difference in change in lower limb protein breakdown

  Time = 165-180 minutes from start of study protocol to approximate Time = 315 minutes from start of study protocol.

• Between-group difference in change in lower limb 3-methylhistidine rate of appearance

  Time = 165-180 minutes from start of study protocol to approximate Time = 315 minutes from start of study protocol.

• Within-group change in lower limb protein balance (experimental group)

  Time = 165-180 minutes from start of study protocol to approximate Time = 315 minutes from start of study protocol.

• Within-group change in lower limb protein balance (active comparator group)

  Time = 165-180 minutes from start of study protocol to approximate Time = 315 minutes from start of study protocol.

Study Arms (2)

IV amino acids + standardized physiotherapy with lower limb resistance exercise.

EXPERIMENTAL

Research subjects randomized to the intervention group will receive an infusion of IV amino acids during a session of protocolized physiotherapy that includes a knee extension resistance exercise targeting the thigh muscles. The supplemental amino acid infusion will continue up until 90 minutes after the subject has returned to bed rest.

Procedure: Resisted knee extension exercise; Drug: IV amino acids

IV amino acids + standardized physiotherapy.

ACTIVE COMPARATOR

Research subjects randomized to the control group will receive an infusion of IV amino acids during a session of protocolized physiotherapy NOT including lower limb resistance exercise. The supplemental amino acid infusion will continue up until 90 minutes after the subject has returned to bed rest.

Drug: IV amino acids

Interventions

Resisted knee extension exercise PROCEDURE

Patients in the intervention group will perform a seated knee extension exercise in three sets. Resistance will be adjusted using ankle weights, targeting 8-12 repetitions per set.

IV amino acids + standardized physiotherapy with lower limb resistance exercise.

IV amino acids DRUG

IV amino acids (Glavamin, Fresenius Kabi) delivered by continuous infusion at a rate of 0.1 g/kg/h. The infusion is started immediately prior to physiotherapy and continued until all blood samples required for outcome assessment are collected during a 90-minute resting period after the exercise session.

Also known as: Glavamin (Fresenius Kabi)

IV amino acids + standardized physiotherapy with lower limb resistance exercise.; IV amino acids + standardized physiotherapy.

Eligibility Criteria

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

You may qualify if:

• Adult (≥18 years) patient admitted to the ICU of the study site.
• Patient deemed suitable for active mobilization by the attending physician and physiotherapist.
• Not expected to be discharged or transferred from the unit within 24 h of enrollment.
• Functioning arterial catheter in situ.

You may not qualify if:

• Not able to provide informed consent.
• Systemic anticoagulation with LMWH/UFH/DOAC in therapeutic dose range for deep vein thrombosis or pulmonary embolism, or dual antiplatelet therapy. If LMWH is administered twice daily, the patient is eligible for participation provided that vascular access is performed at nadir prior to the first daily dose.
• Clinically significant inherited or acquired disorder of hemostasis.
• Morbid obesity that interferes with femoral cannulation or doppler measurements.
• Hemodynamic instability requiring ongoing volume resuscitation with crystalloid solutions or blood products.
• Lower-limb amputee.
• Lower-limb artherosclerotic disease with critical ischemia.
• Metastatic cancer or active hematological malignancy.
• Inherited disorder of amino acid metabolism.
• Chronic muscle, neuromuscular and neurologic disease with prior documentation of clinically significant lower-limb involvement.
• Pregnancy.
• CAM-ICU screening positive for delirium.
• Single organ failure not requiring invasive mechanical ventilation prior to enrollment.

Sponsors & Collaborators

• Karolinska University Hospital: lead

Study Sites (1)

Karolinska University Hospital

Huddinge, Stockholm County, 14186, Sweden

Location

Related Publications (9)

• Batt J, Herridge MS, Dos Santos CC. From skeletal muscle weakness to functional outcomes following critical illness: a translational biology perspective. Thorax. 2019 Nov;74(11):1091-1098. doi: 10.1136/thoraxjnl-2016-208312. Epub 2019 Aug 20.

  PMID: 31431489 BACKGROUND

• Herridge MS, Tansey CM, Matte A, Tomlinson G, Diaz-Granados N, Cooper A, Guest CB, Mazer CD, Mehta S, Stewart TE, Kudlow P, Cook D, Slutsky AS, Cheung AM; Canadian Critical Care Trials Group. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 2011 Apr 7;364(14):1293-304. doi: 10.1056/NEJMoa1011802.

  PMID: 21470008 BACKGROUND

• Plank LD, Connolly AB, Hill GL. Sequential changes in the metabolic response in severely septic patients during the first 23 days after the onset of peritonitis. Ann Surg. 1998 Aug;228(2):146-58. doi: 10.1097/00000658-199808000-00002.

  PMID: 9712558 BACKGROUND

• Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, Hopkinson NS, Phadke R, Dew T, Sidhu PS, Velloso C, Seymour J, Agley CC, Selby A, Limb M, Edwards LM, Smith K, Rowlerson A, Rennie MJ, Moxham J, Harridge SD, Hart N, Montgomery HE. Acute skeletal muscle wasting in critical illness. JAMA. 2013 Oct 16;310(15):1591-600. doi: 10.1001/jama.2013.278481.

  PMID: 24108501 BACKGROUND

• Wolfe RR. Skeletal muscle protein metabolism and resistance exercise. J Nutr. 2006 Feb;136(2):525S-528S. doi: 10.1093/jn/136.2.525S.

  PMID: 16424140 BACKGROUND

• Doiron KA, Hoffmann TC, Beller EM. Early intervention (mobilization or active exercise) for critically ill adults in the intensive care unit. Cochrane Database Syst Rev. 2018 Mar 27;3(3):CD010754. doi: 10.1002/14651858.CD010754.pub2.

  PMID: 29582429 BACKGROUND

• Connolly B, Salisbury L, O'Neill B, Geneen L, Douiri A, Grocott MP, Hart N, Walsh TS, Blackwood B; ERACIP Group. Exercise rehabilitation following intensive care unit discharge for recovery from critical illness. Cochrane Database Syst Rev. 2015 Jun 22;2015(6):CD008632. doi: 10.1002/14651858.CD008632.pub2.

  PMID: 26098746 BACKGROUND

• Fossat G, Baudin F, Courtes L, Bobet S, Dupont A, Bretagnol A, Benzekri-Lefevre D, Kamel T, Muller G, Bercault N, Barbier F, Runge I, Nay MA, Skarzynski M, Mathonnet A, Boulain T. Effect of In-Bed Leg Cycling and Electrical Stimulation of the Quadriceps on Global Muscle Strength in Critically Ill Adults: A Randomized Clinical Trial. JAMA. 2018 Jul 24;320(4):368-378. doi: 10.1001/jama.2018.9592.

  PMID: 30043066 BACKGROUND

• Hickmann CE, Castanares-Zapatero D, Deldicque L, Van den Bergh P, Caty G, Robert A, Roeseler J, Francaux M, Laterre PF. Impact of Very Early Physical Therapy During Septic Shock on Skeletal Muscle: A Randomized Controlled Trial. Crit Care Med. 2018 Sep;46(9):1436-1443. doi: 10.1097/CCM.0000000000003263.

  PMID: 29957714 BACKGROUND

MeSH Terms

Conditions

Critical Illness; Muscular Atrophy

Interventions

Amino Acids

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amino Acids, Peptides, and Proteins

Study Officials

• Martin Sundström Rehal, MD PhD

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

• Olav Rooyackers, PhD

  Karolinska Institutet

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 5, 2022
• First Posted: January 19, 2022
• Study Start: December 25, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 7, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)