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Investigating the Anabolic Response to Resistance Exercise After Critical Illness (ARTIST-2) (ARTIST-2)

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ClinicalTrials.gov Identifier: NCT05261984
Recruitment Status : Recruiting
First Posted : March 2, 2022
Last Update Posted : June 3, 2022
Sponsor:
Information provided by (Responsible Party):
Martin Sundstrom Rehal, 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.


Condition or disease Intervention/treatment Phase
Critical Illness Muscle Loss Procedure: Resistance exercise Dietary Supplement: Oral protein supplementation Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Investigating the Anabolic Response to Resistance Exercise After Critical Illness: The ARTIST-2 Non-Randomized Controlled Trial
Actual Study Start Date : March 8, 2022
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Former ICU patients
Research subjects with a prior history of ICU treatment within six months.
Procedure: Resistance exercise
Weighted knee extensions in four sets targeting 8-12 repetitions to failure.

Dietary Supplement: Oral protein supplementation
24 grams of hydrolyzed whey protein.

Active Comparator: Age- and sex-matched control group
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.
Procedure: Resistance exercise
Weighted knee extensions in four sets targeting 8-12 repetitions to failure.

Dietary Supplement: Oral protein supplementation
24 grams of hydrolyzed whey protein.




Primary Outcome Measures :
  1. Muscle protein fractional synthetic rate [ Time Frame: 150 minutes post-exercise. ]
    The difference between the experimental and active comparator group in muscle protein fractional synthetic rate.


Secondary Outcome Measures :
  1. Gene expression [ Time Frame: 150 minutes post-exercise. ]
    The difference between the experimental and active comparator group in gene expression (mRNA) in skeletal muscle, assessed by RNA sequencing.

  2. Signaling pathways [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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 within the last 30 years

Exclusion Criteria:

  1. Not able to provide informed consent
  2. >6 months since ICU discharge*
  3. Systemic anticoagulation with LMWH/UFH/DOAC in therapeutic dose range for deep vein thrombosis or pulmonary embolism, or dual antiplatelet therapy
  4. Clinically significant inherited or acquired disorder of hemostasis
  5. Lower-limb amputee
  6. Lower-limb atherosclerotic disease with critical ischemia.
  7. Recent fracture in lower limbs or significant osteoarthritis limiting movement in knee or hip joint
  8. Metastatic cancer or active hematological malignancy
  9. Inherited disorder of amino acid metabolism.
  10. Chronic muscle, neuromuscular or neurologic disease with prior documentation of clinically significant lower-limb involvement
  11. Pregnancy
  12. Single organ failure not requiring invasive mechanical ventilation during ICU stay*

Exclusion criteria marked with asterisk only apply to former ICU patients.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05261984


Contacts
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Contact: Martin Sundström Rehal, MD PhD +48-8-58580000 martin.sundstrom@gmail.com
Contact: Arabella Fischer, MD PhD arabella.fischer@meduniwien.ac.at

Locations
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Sweden
Karolinska University Hospital Recruiting
Huddinge, Stockholm, Sweden, 14186
Contact: Martin Sundström Rehal, MD PhD    +46-8-58580000    martin.sundstrom@gmail.com   
Sponsors and Collaborators
Karolinska University Hospital
Investigators
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Principal Investigator: Martin Sundström Rehal, MD PhD Karolinska University Hospital
Study Chair: Olav Rooyackers, PhD Karolinska University Hospital
Publications:

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Responsible Party: Martin Sundstrom Rehal, Principal Investigator, Karolinska University Hospital
ClinicalTrials.gov Identifier: NCT05261984    
Other Study ID Numbers: K 2022-1113
First Posted: March 2, 2022    Key Record Dates
Last Update Posted: June 3, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Martin Sundstrom Rehal, Karolinska University Hospital:
Resistance exercise
Muscle protein
Anabolic resistance
Additional relevant MeSH terms:
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Critical Illness
Disease Attributes
Pathologic Processes