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

NCT ID: NCT02469337

Last Updated: 2017-01-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2017-06-30

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Carbohydrate drinks

Intervention Type: DIETARY_SUPPLEMENT

preoperative carbohydrate drinks

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.

Group Type: ACTIVE_COMPARATOR

Dichloroacetate

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Moderate intensity exercise

Intervention Type: BEHAVIORAL

30 min exercise using a semi-recumbent exercise bike, at about 70% of their age estimated heart rate

Control

Patients in this group will have surgery as standard practice with none of the above interventions

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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

Intervention Type: DRUG

Carbohydrate drinks

preoperative carbohydrate drinks

Intervention Type: DIETARY_SUPPLEMENT

Moderate intensity exercise

30 min exercise using a semi-recumbent exercise bike, at about 70% of their age estimated heart rate

Intervention Type: BEHAVIORAL

Other Intervention Names

sodium dichloroacetate

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Nottingham

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dileep N Lobo, Professor

Role: PRINCIPAL_INVESTIGATOR

University of Nottingham

Locations

University Hospitals Nottingham Queen's Medical Centre

Nottingham, Nottingham, United Kingdom

Countries

United Kingdom

Other Identifiers

11/EE/0395

Identifier Type: -

Identifier Source: org_study_id