Investigating the Anabolic Response to Resistance Exercise After Critical Illness (ARTIST-2)
- Conditions
- Critical IllnessMuscle Loss
- Interventions
- Procedure: Resistance exerciseDietary Supplement: Oral protein supplementation
- Registration Number
- NCT05261984
- Lead Sponsor
- Karolinska University Hospital
- Brief Summary
ICU survivors often suffer from long-term functional disability. An attenuated response to physical exercise in skeletal muscle after critical illness may contribute to persisting weakness.
The aim of this study is to investigate the effects of resistance exercise on muscle protein synthesis in former ICU patients. The investigators hypothesize that study subjects recovering from critical illness have an impaired anabolic response to resistance exercise after ICU stay as compared to non-critically ill controls.
- 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 may persists for several years in ICU survivors. It has significant long-term consequences, and is associated with increased health care costs, delayed return to work, and overall poor quality of life.
Muscle atrophy is a major contributor to ICUAW. Critical illness is associated with a rapid loss of skeletal muscle, induced by catabolic signals from proinflammatory cytokines and hormones. The ability to regain lost muscle mass during convalescence may also be impaired. In a small observational study, muscle atrophy resolved only in a minority of ICU survivors at six months after ICU discharge.
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 reconstitute muscle mass after critical illness. Despite several clinical trials, there is equipoise regarding the efficacy of exercise in improving physical function in-ICU after ICU discharge. These mixed signals are unsurprising given the heterogeneous causes of ICUAW.
Only a few studies in this field have examined 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 effects on protein synthesis and breakdown. There is still no published research using this methodology to assess the effects of exercise interventions in former ICU patients. To understand the role of physical exercise in regaining lost muscle mass, the investigators plan to investigate the anabolic effects to resistance training after critical illness.
Aim and hypothesis
The aim of this study is to determine the anabolic response to resistance exercise after critical illness. The investigators hypothesize that study subjects recovering from critical illness have an impaired anabolic response to resistance exercise after ICU stay as compared to non-critically ill controls.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
-
Adult (≥18 years) previously admitted to an ICU at Karolinska University Hospital for ≥3 days and discharged alive from hospital
OR
-
Adult (≥18 years) without a history of ICU admission (control group)
- Not able to provide informed consent
- >6 months since ICU discharge*
- Warfarin or dual antiplatelet therapy
- Clinically significant inherited or acquired disorder of hemostasis
- Lower-limb amputee
- Lower-limb atherosclerotic disease with critical ischemia.
- Recent fracture in lower limbs or significant osteoarthritis limiting movement in knee or hip joint
- Metastatic cancer or active hematological malignancy
- Inherited disorder of amino acid metabolism.
- Chronic muscle, neuromuscular or neurologic disease with prior documentation of clinically significant lower-limb involvement
- Pregnancy
- Single organ failure not requiring invasive mechanical ventilation during ICU stay*
- Intubated only for airway protection with no other organ failure(s) during ICU stay*
- Planned postoperative care in ICU after elective cardiothoracic surgery*
Exclusion criteria marked with asterisk only apply to former ICU patients.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Former ICU patients Resistance exercise Research subjects with a prior history of ICU treatment within six months. Former ICU patients Oral protein supplementation Research subjects with a prior history of ICU treatment within six months. Age- and sex-matched control group Oral protein supplementation Research subjects without a prior history of ICU treatment within the last 30 years, age- and sex-matched in a 1:2 ratio to the experimental arm. Age- and sex-matched control group Resistance exercise Research subjects without a prior history of ICU treatment within the last 30 years, age- and sex-matched in a 1:2 ratio to the experimental arm.
- Primary Outcome Measures
Name Time Method Muscle protein fractional synthetic rate 150 minutes post-exercise. The difference between the experimental and active comparator group in muscle protein fractional synthetic rate.
- Secondary Outcome Measures
Name Time Method Gene expression 150 minutes post-exercise. The difference between the experimental and active comparator group in gene expression (mRNA) in skeletal muscle, assessed by RNA sequencing.
Signaling pathways 150 minutes post-exercise. The difference between the experimental and active comparator group in the activity of major anabolic/catabolic signalining pathways in skeletal muscle, assessed by western blot.
Trial Locations
- Locations (1)
Karolinska University Hospital
🇸🇪Huddinge, Stockholm, Sweden