Insulin ResistancePhase 4CARBEXNCT02469337
Role of Preoperative Carbohydrates Drinks, Dichloroacetate and Exercise on Postoperative Muscle Insulin Resistance
A Phase 4 study testing Dichloroacetate, Carbohydrate drinks and Moderate intensity exercise in people with Insulin Resistance, run by University of Nottingham at 1 site in United Kingdom.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Insulin Resistance
- What is being tested?
- Dichloroacetate, Carbohydrate drinks and Moderate intensity exercise
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2012to Jun 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Patients who are
- Undergoing emergency surgery
- Suffering from chronic illness, (e.g. diabetes) or other debilitating diseases
- On long term anti-inflammatory drugs, (e.g. NSAIDS, Steroids, immunosuppressant)
- On long term antibiotics
- On Statins
Show all 10Show fewer
- On full therapeutic dose of anticoagulants, or aspirin >325 mg/day, Clopidrogel >75mg/day
- Suffering from bleeding diathesis
- Unable to give consent
- Pregnant or breastfeeding.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University Hospitals Nottingham Queen's Medical Centre
Nottingham, Nottingham, NG7 2UH
About this study
Official title: Randomized Control Trial of Dichloroacetate, Preoperative Carbohydrate Loading and Moderate Intensity Exercise on Muscle Insulin Resistance After Major Abdominal Surgery
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.
Read the 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
- Being tested
- Dichloroacetate, Carbohydrate drinks, Moderate intensity exercise
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DichloroacetateDrug
Also called sodium 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
Carbohydrate drinksDietary supplement
preoperative carbohydrate drinks
Moderate intensity exerciseBehavioural
30 min exercise using a semi-recumbent exercise bike, at about 70% of their age estimated heart rate
| Study group | Role | What they receive |
|---|---|---|
| Preoperative carbohydrate drinks | Active comparator | 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. Receives: Dietary Supplement: Carbohydrate drinks |
| Dichloroacetate infusion | Active comparator | 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. Receives: Drug: Dichloroacetate |
| Moderate intensity exercise | Active comparator | 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. Receives: Behavioral: Moderate intensity exercise |
| Control | No intervention | Patients in this group will have surgery as standard practice with none of the above interventions |
What is being measured
The primary outcome is the main question the study is designed to answer.
insulin resistance
Relative changes in indices of muscle insulin resistance namely PDC activity, PDK4 mRNA and protein expression.
Measured: 48 hours after surgery
Secondary outcomes (2)
muscle carbohydrate oxidation
Changes in muscle metabolites such as glycogen, glucose, lactate, reflecting the changes in skeletal muscle carbohydrate oxidation.
Measured: 48 hours after surgery
Mitochondrial ATP production
Mitochondrial ATP production rates in patients undergoing major abdominal surgery.
Measured: 48 hours after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2015 (estimated)
- Study startMay 2012
- Primary completionJun 2017 (estimated)
- Study completionJun 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Insulin ResistanceStudies of the same condition, open and under way.
- More trials run by University of NottinghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dileep N Lobo, Professor, Principal investigator, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02469337
- Sponsor's protocol ID
- 11/EE/0395
- Acronym
- CARBEX
- Status last verified
- Jan 2017
- First submitted
- 8 Jun 2015
- Last updated
- 5 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Control Trial of Dichloroacetate, Preoperative Carbohydrate Loading and Moderate Intensity Exercise on Muscle Insulin Resistance After Major Abdominal Surgery
- ClinicalTrials.gov ID
- NCT02469337
- Acronym / sponsor ID
- CARBEX / 11/EE/0395
- Conditions
- Insulin Resistance
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Study start
- May 2012
- Primary completion
- Jun 2017 (estimated)
- Study completion
- Jun 2017 (estimated)
- First posted
- 11 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Preoperative carbohydrate drinks | Active comparator | Dietary Supplement: Carbohydrate drinksPatients 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. |
| Dichloroacetate infusion | Active comparator | Drug: DichloroacetateThe 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. |
| Moderate intensity exercise | Active comparator | Behavioral: Moderate intensity exercisePatients 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. |
| Control | No intervention | –Patients in this group will have surgery as standard practice with none of the above interventions |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (10 listed)
- Patients who are
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DichloroacetateAlso: sodium dichloroacetateDichloroacetate, 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 | Drug | Dichloroacetate infusion |
| Carbohydrate drinkspreoperative carbohydrate drinks | Dietary supplement | Preoperative carbohydrate drinks |
| Moderate intensity exercise30 min exercise using a semi-recumbent exercise bike, at about 70% of their age estimated heart rate | Behavioural | Moderate intensity exercise |
Primary outcome
insulin resistance
Time frame: 48 hours after surgery
Relative changes in indices of muscle insulin resistance namely PDC activity, PDK4 mRNA and protein expression.
2 secondary outcomes
muscle carbohydrate oxidation
Time frame: 48 hours after surgery
Mitochondrial ATP production
Time frame: 48 hours after surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2017.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dileep N Lobo, Professor principal investigator
University of Nottingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dichloroacetate, Carbohydrate drinks and Moderate intensity exercise in people with Insulin Resistance, run by University of Nottingham at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
insulin resistance (time frame: 48 hours after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2017.