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

Insulin Resistance Clinical Trial

— CARBEX  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02469337
• Other study ID #: 11/EE/0395
• Status: Active, not recruiting
• Phase: Phase 4
• First received: June 8, 2015
• Last updated: January 4, 2017
• Start date: May 2012
• Est. completion date: June 2017

Study information

• Verified date: January 2017
• Source: University of Nottingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: June 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Insulin Resistance

Intervention

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

Locations

Country	Name	City	State
United Kingdom	University Hospitals Nottingham Queen's Medical Centre	Nottingham

Sponsors (1)

Lead Sponsor	Collaborator
University of Nottingham

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	insulin resistance	Relative changes in indices of muscle insulin resistance namely PDC activity, PDK4 mRNA and protein expression.	48 hours after surgery	No
Secondary	muscle carbohydrate oxidation	Changes in muscle metabolites such as glycogen, glucose, lactate, reflecting the changes in skeletal muscle carbohydrate oxidation.	48 hours after surgery	No
Secondary	Mitochondrial ATP production	Mitochondrial ATP production rates in patients undergoing major abdominal surgery.	48 hours after surgery	No