Investigating the Anabolic Response to Resistance Exercise During Critical Illness (ARTIST-1)

Karolinska University Hospital

Status: Suspended

Conditions: Critical Illness; Muscle Loss

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

Study type: Interventional

Funder types: Other

Identifiers

NCT05197231

K 2021-10530

Details and patient eligibility

About

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.

Full description

Background

The debilitating impact of critical illness has been recognized for several decades. Disability related to intensive care is now described as a syndrome called ICU-acquired weakness (ICUAW). ICUAW affects up to 70% of ICU patients and is most common with higher illness severity. Patients that develop ICUAW require longer hospitalization and have a higher risk of death. Weakness also has significant long-term consequences, and is associated with significant health care costs, delayed return to work, and overall poor quality of life.

Preventing or reducing muscle atrophy is a potential way to counteract weakness. Critical illness is associated with a rapid loss of skeletal muscle. Studies in exercise physiology have demonstrated that resistance training and amino acid ingestion have synergistic effects on muscle protein synthesis in healthy subjects. It is therefore an appealing therapy to counteract muscle wasting in the ICU.

Despite several clinical trials, there is equipoise regarding the efficacy of exercise in improving physical function in-ICU or after discharge. These mixed signals are unsurprising given the heterogeneous causes of ICUAW. Only a few studies in this field assess muscle architecture or cellular signaling in response to training. However, the gold standard in determining the anabolic response to exercise is to directly measure the effect on protein synthesis and breakdown. To our knowledge there is still no published research using this methodology to assess the effects of exercise interventions in critically ill patients.

Aim and hypothesis

The overall aim of this project is to determine the anabolic response to resistance exercise during critical illness. The investigators hypothesize that resistance exercise, in addition to amino acid supplementation and routine physiotherapy, results in an improved muscle protein balance in ICU patients compared to amino acid supplementation and routine physiotherapy alone (primary outcome). The effect of the intervention on other parameters of muscle protein kinetics and within-group differences in protein kinetics before and after physiotherapy will be assessed as secondary outcome measures.

Enrollment: 24 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

1. Not able to provide informed consent.
2. 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.
3. Clinically significant inherited or acquired disorder of hemostasis.
4. Morbid obesity that interferes with femoral cannulation or doppler measurements.
5. Hemodynamic instability requiring ongoing volume resuscitation with crystalloid solutions or blood products.
6. Lower-limb amputee.
7. Lower-limb artherosclerotic disease with critical ischemia.
8. Metastatic cancer or active hematological malignancy.
9. Inherited disorder of amino acid metabolism.
10. Chronic muscle, neuromuscular and neurologic disease with prior documentation of clinically significant lower-limb involvement.
11. Pregnancy.
12. CAM-ICU screening positive for delirium.
13. Single organ failure not requiring invasive mechanical ventilation prior to enrollment.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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24 participants in 2 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: IV amino acids

Procedure: Resisted knee extension exercise

IV amino acids + standardized physiotherapy.

Active Comparator group

Description:

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.

Treatment:

Drug: IV amino acids