Investigating the Anabolic Response to Resistance Exercise During Critical Illness: The ARTIST-1 Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 暂停
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Between-group difference in change in lower limb protein balance
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
- •CAM-ICU screening positive for delirium.
- •Single organ failure not requiring invasive mechanical ventilation prior to enrollment.
研究组 & 干预措施
IV amino acids + standardized physiotherapy with lower limb resistance exercise.
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.
干预措施: Resisted knee extension exercise (Procedure)
IV amino acids + standardized physiotherapy with lower limb resistance exercise.
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.
干预措施: IV amino acids (Drug)
IV amino acids + standardized physiotherapy.
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.
干预措施: IV amino acids (Drug)
结局指标
主要结局
Between-group difference in change in lower limb protein balance
时间窗: Time = 165-180 minutes from start of study protocol to approximate Time = 315 minutes from start of study protocol.
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.
次要结局
- 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.)
- Within-group change in lower limb protein breakdown (active comparator 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 (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.)
- Within-group change in lower limb protein breakdown (experimental group)(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 synthesis (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 synthesis (active comparator 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 3-methylhistidine rate of appearance (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 3-methylhistidine rate of appearance (active comparator group)(Time = 165-180 minutes from start of study protocol to approximate Time = 315 minutes from start of study protocol.)
研究者
Martin Sundstrom Rehal
Principal Investigator
Karolinska University Hospital