Role of Preoperative Carbohydrates Drinks, Dichloroacetate and Exercise on Postoperative Muscle Insulin Resistance (CARBEX)
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|ClinicalTrials.gov Identifier: NCT02469337|
Recruitment Status : Unknown
Verified January 2017 by University of Nottingham.
Recruitment status was: Active, not recruiting
First Posted : June 11, 2015
Last Update Posted : January 5, 2017
|Condition or disease||Intervention/treatment||Phase|
|Insulin Resistance||Drug: Dichloroacetate Dietary Supplement: Carbohydrate drinks Behavioral: Moderate intensity exercise||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Randomized Control Trial of Dichloroacetate, Preoperative Carbohydrate Loading and Moderate Intensity Exercise on Muscle Insulin Resistance After Major Abdominal Surgery|
|Study Start Date :||May 2012|
|Estimated Primary Completion Date :||June 2017|
|Estimated Study Completion Date :||June 2017|
Active Comparator: 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.
Dietary Supplement: Carbohydrate drinks
preoperative carbohydrate drinks
Active Comparator: 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.
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
Other Name: sodium dichloroacetate
Active Comparator: 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.
Behavioral: Moderate intensity exercise
30 min exercise using a semi-recumbent exercise bike, at about 70% of their age estimated heart rate
No Intervention: Control
Patients in this group will have surgery as standard practice with none of the above interventions
- insulin resistance [ Time Frame: 48 hours after surgery ]Relative changes in indices of muscle insulin resistance namely PDC activity, PDK4 mRNA and protein expression.
- muscle carbohydrate oxidation [ Time Frame: 48 hours after surgery ]Changes in muscle metabolites such as glycogen, glucose, lactate, reflecting the changes in skeletal muscle carbohydrate oxidation.
- Mitochondrial ATP production [ Time Frame: 48 hours after surgery ]Mitochondrial ATP production rates in patients undergoing major abdominal surgery.
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): NCT02469337
|University Hospitals Nottingham Queen's Medical Centre|
|Nottingham, United Kingdom, NG7 2UH|
|Principal Investigator:||Dileep N Lobo, Professor||University of Nottingham|