Effects of Ketosis on Muscle Kinetics and Signaling During Critical Illness.
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Net leg phenylalanine release
研究概览
简要总结
Background:
Patients with critical illness in the intensive care unit (ICU) experience marked skeletal muscle weakness, muscle atrophy and disability in physical function, commonly termed ICU-acquired weakness (ICU-AW). The pathophysiology of ICU-AW is complex, but a key feature of skeletal muscle wasting is disturbed protein metabolism reflected in both increased rate of muscle protein degradation and reduced synthesis. Treatment with 3-OHB seems a promising new anticatabolic treatment in patients with critical illness, preventing ICU-AW. To date, no data exist on the clinical and functional effects of ketone body modulation in patients with critical illness.
Objective:
The aim to investigate the effect of exogenous 3-OHB administration on muscle protein kinetics and lipolysis in patients with critical illness, aiming towards preventing ICU-AW.
Design:
A randomized double-blind isocaloric placebo-controlled cross-over study in 10 mechanically ventilated patients with critical illness in the ICU.
Methods:
Evaluation of whole-body and focal leg protein kinetics using labeled phenylalanine and tyrosine tracers. Assessment of free fatty acid (FFA) turnover using a labeled palmitate tracer. Femoral arterial blood flow (assessed with pulsed-wave Doppler ultrasound) is evaluated once per study period. Blood- and urinary samples are collected routinely throughout the study day. Whenever feasible, muscle and fat biopsies will be taken for analysis of protein and adipocyte metabolic signaling and mitochondrial function.
Perspectives: This investigation may grant essential knowledge on ketosis in critical illness. This may lead to larger clinical trials, and hopefully a new and better treatment strategy aimed at preserving muscle mass and function during and improving recovery after critical illness.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Invasive mechanical ventilation via a cuffed endotracheal or tracheotomy tube.
- •Expected survival of ICU admission.
- •Adults (≥18 years).
- •Multi-organ failure (Sequential Organ Failure Assessment Score [SOFA] score ≥2 in 2 or more domains).
排除标准
- •Moribund or expected withholding treatment within 48 hours as judged by the investigator.
- •Palliative goals of care.
- •Contraindication for enteral nutrition.
- •Pregnancy.
- •Known severe musculoskeletal or neurological disability.
- •Diabetic ketoacidosis.
- •Phenylketonuria.
- •BMI ≤17 or deemed malnourished as judged by the investigator.
- •BMI >40.
结局指标
主要结局
Net leg phenylalanine release
时间窗: 3 hours
As measured by rate of phenylalanine appearance in relation with the rate of disappearance.
次要结局
- Changes in intramyocellular protein metabolic signalling pathways.(3 hours.)
- Change in rate of appearance of phenylalanine over the leg.(3 hours.)
- Change in rate of disappearance of phenylalanine over the leg.(3 hours.)
- Whole body palmitate flux(3 hours.)
- Change in arterial pH.(3 hours.)
- Changes in inflammatory cytokines (IL-1, IL-6, IL-18, TNFa)(3 hours.)
研究者
Kristoffer Berg-Hansen
MD, Principal Investigator
Aarhus University Hospital