Randomized Control Trial of Dichloroacetate, Preoperative Carbohydrate Loading and Moderate Intensity Exercise on Muscle Insulin Resistance After Major Abdominal Surgery
试验速览
- 阶段
- 4 期
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- insulin resistance
研究概览
简要总结
The aim of the study is to investigate whether preoperative interventions such as carbohydrate drinks, Dichloroacetate and exercise would inhibit or reverse the changes in molecular mechanisms regulating muscle carbohydrate oxidation and postoperative muscle insulin resistance in patients undergoing major abdominal surgery.
详细描述
Forty patients undergoing open elective gastrointestinal surgery, will be randomized to four groups of 10 each. The patients will be randomised to receive either preoperative (1) oral carbohydrate drinks (CHO) or (2) infusion of Dichloroacetate with oral carbohydrate drinks (3) exercise or (4) standard care.
Since the interventions are qualitatively different and only the physiological mechanisms are being studied rather than the clinical outcomes, the study is not blinded and no placebo is used.
Analysis for cytokines, insulin, glucagon levels will be performed at screening, during surgery and on the 2nd postoperative day. Muscle biopsies will be taken at the beginning and end of surgery, from rectus abdominus and vastus lateralis muscles for analysis of mRNA (IL-6, TNF-α, Akt1, IRS-1, FOXO1, MAFbx, MURF1 and PDK4) and protein (MafBx, FOXO1, PDK4) expression and muscle metabolites (glycogen, lactate, triglycerides and FFA). Oral Glucose Tolerance Test (GTT) to be performed at the screening visit and on the 2nd postoperative day using a standard protocol. The techniques to be employed to study the above will include RT-PCR, radioimmunoassay, spectophotometry, bioluminometry, Western blotting and ELISA.
Primary outcome: The changes in indices of muscle insulin resistance and muscle protein breakdown at the beginning and at the end of surgery, in response to surgical stress.
Secondary outcomes: (a) The expression of muscle metabolites, reflecting muscle protein turnover (b) Clinical Outcomes: Length of stay and incidence of postoperative complications.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
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
- •All patients over 18 years of age, who are undergoing major elective open abdominal surgery will be included in the study. Patients should be able to provide a written informed consent to participate in the study.
排除标准
- •Patients who are
- •Undergoing emergency surgery
- •Suffering from chronic illness, (e.g. diabetes) or other debilitating diseases
- •On long term anti-inflammatory drugs, (e.g. NSAIDS, Steroids, immunosuppressant)
- •On long term antibiotics
- •On full therapeutic dose of anticoagulants, or aspirin >325 mg/day, Clopidrogel >75mg/day
- •Suffering from bleeding diathesis
- •Unable to give consent
- •Pregnant or breastfeeding.
研究组 & 干预措施
Preoperative carbohydrate drinks
Patients who were randomised to carbohydrate group ingested 800ml PreOp (Nutricia Clinical Care, 12.5g CHO/100 ml) the night before and 400ml in the morning of surgery, about 2-3 hours before the induction of anaesthesia.
干预措施: Carbohydrate drinks (Dietary Supplement)
Dichloroacetate infusion
The patients in the dichloroacetate group received the CHO drinks as well as an intravenous infusion of DCA (50mg/kg body weight) over 45 min, one- two hours before the induction of anaesthesia.
干预措施: Dichloroacetate (Drug)
Moderate intensity exercise
Patients randomised to exercise group, will perform a 30 min exercise using a semi-recumbent exercise bike, at about 70% of their age estimated heart rate(determined by the formula: (220-Age)*0.7 under close supervision and monitoring of their vital parameters.
干预措施: Moderate intensity exercise (Behavioral)
结局指标
主要结局
insulin resistance
时间窗: 48 hours after surgery
Relative changes in indices of muscle insulin resistance namely PDC activity, PDK4 mRNA and protein expression.
次要结局
- muscle carbohydrate oxidation(48 hours after surgery)
- Mitochondrial ATP production(48 hours after surgery)