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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
Sponsor:
Information provided by (Responsible Party):
University of Nottingham

Brief 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.

Condition or disease Intervention/treatment Phase
Insulin Resistance Drug: Dichloroacetate Dietary Supplement: Carbohydrate drinks Behavioral: Moderate intensity exercise Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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
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



Primary Outcome Measures :
  1. insulin resistance [ Time Frame: 48 hours after surgery ]
    Relative changes in indices of muscle insulin resistance namely PDC activity, PDK4 mRNA and protein expression.


Secondary Outcome Measures :
  1. 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.

  2. Mitochondrial ATP production [ Time Frame: 48 hours after surgery ]
    Mitochondrial ATP production rates in patients undergoing major abdominal surgery.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Patients who are

    1. Undergoing emergency surgery
    2. Suffering from chronic illness, (e.g. diabetes) or other debilitating diseases
    3. On long term anti-inflammatory drugs, (e.g. NSAIDS, Steroids, immunosuppressant)
    4. On long term antibiotics
    5. On Statins
    6. On full therapeutic dose of anticoagulants, or aspirin >325 mg/day, Clopidrogel >75mg/day
    7. Suffering from bleeding diathesis
    8. Unable to give consent
    9. Pregnant or breastfeeding.

Information from the National Library of Medicine

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


Locations
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United Kingdom
University Hospitals Nottingham Queen's Medical Centre
Nottingham, United Kingdom, NG7 2UH
Sponsors and Collaborators
University of Nottingham
Investigators
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Principal Investigator: Dileep N Lobo, Professor University of Nottingham
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Responsible Party: University of Nottingham
ClinicalTrials.gov Identifier: NCT02469337    
Other Study ID Numbers: 11/EE/0395
First Posted: June 11, 2015    Key Record Dates
Last Update Posted: January 5, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases