Clinical trial NCT05197231: Investigating the Anabolic Response to Resistance Exercise During Critical Illness
Official title: Investigating the Anabolic Response to Resistance Exercise During Critical Illness: The ARTIST-1 Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: NA
Conditions: Critical Illness
Muscle Loss
Keywords: Physiotherapy
Resistance exercise
Amino acids
Muscle protein balance
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
First posted: 2022-01-19
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Between-group difference in change in lower limb protein balance
timeFrame: Time = 165-180 minutes from start of study protocol to approximate Time = 315 minutes from start of study protocol.
Secondary outcomes:
measure: Between-group difference in change in lower limb protein synthesis
timeFrame: Time = 165-180 minutes from start of study protocol to approximate Time = 315 minutes from start of study protocol.
measure: Between-group difference in change in lower limb protein breakdown
timeFrame: Time = 165-180 minutes from start of study protocol to approximate Time = 315 minutes from start of study protocol.
measure: Between-group difference in change in lower limb 3-methylhistidine rate of appearance
timeFrame: Time = 165-180 minutes from start of study protocol to approximate Time = 315 minutes from start of study protocol.
measure: Within-group change in lower limb protein balance (experimental group)
timeFrame: Time = 165-180 minutes from start of study protocol to approximate Time = 315 minutes from start of study protocol.
measure: Within-group change in lower limb protein balance (active comparator group)
timeFrame: Time = 165-180 minutes from start of study protocol to approximate Time = 315 minutes from start of study protocol.
measure: Within-group change in lower limb protein synthesis (experimental group)
timeFrame: Time = 165-180 minutes from start of study protocol to approximate Time = 315 minutes from start of study protocol.
measure: Within-group change in lower limb protein synthesis (active comparator group)
timeFrame: Time = 165-180 minutes from start of study protocol to approximate Time = 315 minutes from start of study protocol.
measure: Within-group change in lower limb protein breakdown (experimental group)
timeFrame: Time = 165-180 minutes from start of study protocol to approximate Time = 315 minutes from start of study protocol.
measure: Within-group change in lower limb protein breakdown (active comparator group)
timeFrame: Time = 165-180 minutes from start of study protocol to approximate Time = 315 minutes from start of study protocol.
measure: Within-group change in lower limb 3-methylhistidine rate of appearance (experimental group)
timeFrame: Time = 165-180 minutes from start of study protocol to approximate Time = 315 minutes from start of study protocol.
measure: Within-group change in lower limb 3-methylhistidine rate of appearance (active comparator group)
timeFrame: Time = 165-180 minutes from start of study protocol to approximate Time = 315 minutes from start of study protocol.
Other outcomes:
Locations:
city: Huddinge
country: Sweden
facility: Karolinska University Hospital
state: Stockholm
Study officials:
affiliation: Karolinska University Hospital
name: Martin Sundström Rehal, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska Institutet
name: Olav Rooyackers, PhD
role: STUDY_CHAIR
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