NCT02469337

Role of Preoperative Carbohydrates Drinks, Dichloroacetate and Exercise on Postoperative Muscle Insulin Resistance

Randomized Control Trial of Dichloroacetate, Preoperative Carbohydrate Loading and Moderate Intensity Exercise on Muscle Insulin Resistance After Major Abdominal Surgery

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: University of Nottingham · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Insulin Resistance

Interventions

Type	Name	Description
DRUG	Dichloroacetate	Dichloroacetate, an analog of acetic acid has been shown to increase the activation of PDC by inhibiting PDK4 in humans. This drug is expected to shift the metabolism of pyruvate from glycolysis and towards oxidative pathway in the mitochondria
DIETARY_SUPPLEMENT	Carbohydrate drinks	preoperative carbohydrate drinks
BEHAVIORAL	Moderate intensity exercise	30 min exercise using a semi-recumbent exercise bike, at about 70% of their age estimated heart rate

Timeline

• Start date: 2012-05-01
• Primary completion: 2017-06-01
• Completion: 2017-06-01
• First posted: 2015-06-11
• Last updated: 2017-01-05

Locations

1 site across 1 country: United Kingdom