Plain English Summary
Background and study aims
Up to 3 million surgical procedures are performed annually in Britain. Although patients may undergo the same operation, some patients go on to develop greater degrees of inflammatory stress than others. This results in certain patients developing marked inflammation and insulin resistance. Insulin resistance means the body does not respond appropriately to important hormones. The degree of insulin resistance the body develops determines whether patients develop serious complications and how rapidly they recover after surgery. We do not know why these stress responses after major surgery differ so greatly between patients, but think this occurs due to the make-up and function of the body's muscle and fatty tissues. By studying and understanding these mechanisms we will be able to identify patients at risk of developing marked stress responses and improve their preparation before surgery, thereby possibly improving the outcomes of thousands of patients undergoing major surgery. Our study will investigate the roles that different types of muscle and fat in the body play in the development of inflammatory stress and insulin resistance. This is of importance as in the UK patients undergoing surgery are becoming more obese. We will also identify better ways of predicting the development of inflammatory stress and insulin resistance in surgical patients. This would allow us to select those patients whom we know will develop marked inflammatory stress and insulin resistance, and optimise their preparation before surgery.
Who can participate?
Patients aged 18-75 due to have a major abdominal operation.
What does the study involve?
Participants are asked to attend the hospital in the week before surgery. We perform some tests to look at the way that the body reacts to insulin (a hormone that allows the body to use energy from food). This involves blood tests, a small muscle biopsy (sample) and a low-dose X-ray. Before surgery, participants are randomly allocated to drink either a carbohydrate (sugary) drink or a placebo (dummy) drink. It is possible that drinking this carbohydrate drink may improve how participants recover following surgery and this is one of the things we want to test in this study. Many studies have demonstrated that drinking these specially designed carbohydrate drinks before surgery is safe. During the operation under general anaesthetic, the surgeon takes a few samples of muscle and fat from your body and a small amount (30ml, three tablespoons) of blood. On the day after the operation, we perform a few more blood tests, take another small muscle biopsy and repeat the test to see how the body responds to insulin after major surgery.
What are the possible benefits and risks of participating?
Although the study (carbohydrate) drink has been previously shown to make patients feel better before/after surgery (less thirst/nausea/vomiting and quicker recovery after surgery) there is no guarantee that participants will experience these benefits. We cannot promise the study will help participants but the information we get will help improve the treatment of future patients who undergo surgery. There is a small risk of bleeding (much less than a 1 in a 100 chance) when we take the muscle/fat biopsies. If this occurs the person performing the biopsy will apply pressure or use a special instrument to stop the bleeding. The muscle or fat biopsies may be uncomfortable but we will inject plenty of local anaesthetic beforehand to numb the area. There is a very small chance of developing side effects when we perform the special tests to see how participants react to insulin. Participants will be monitored with a heart monitor and blood pressure measurement and a study doctor will always be present during the insulin infusion.
Where is the study run from?
The study is taking place at Queens Medical Centre, Nottingham and the University of Nottingham Medical School (which is on the Queens Medical Centre site).
When is the study starting and how long is it expected to run for?
September 2011 to September 2013
Who is funding the study?
The study is being funded by CORE charity, The European Society for Clinical Nutrition and Metabolism (ESPEN), Nottingham Digestive Diseases Centre NIHR Biomedical Research Unit, the Division of Gastrointestinal Surgery and the School of Biomedical Sciences (University of Nottingham).
Who is the main contact?
Prof. Dileep Lobo
leep.lobo@nottingham.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Prof Dileep Lobo
ORCID ID
Contact details
Queen's Medical Centre
Derby Road
Nottingham
NG7 2UH
United Kingdom
-
dileep.lobo@nottingham.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
11276
Study information
Scientific title
Investigating whether the magnitude of postoperative inflammatory and insulin resistant responses is related to body composition and physiological function of skeletal muscle and adipose tissue: a randomised controlled trial
Acronym
Study hypothesis
Preoperative fasting and surgery induce stress, inflammation and insulin resistance (IR). The development of IR is clinically significant as it increases length of hospital stay, surgical morbidity and mortality. A recent study demonstrated that for every 1mg/kg/min decrease in intraoperative insulin sensitivity (i.e. IR), the development of major postoperative complications is increased (OR 2.23, P=0.004). Measures to attenuate IR may, therefore, be of clinical benefit. Such measures include administering carbohydrate-based drinks preoperatively. Surgical patients undergoing the same operative procedure develop differing magnitudes of IR postoperatively, however, the reasons underlying this remains unknown. To date, few studies have examined whether differences in body composition and physiology contribute to the development of postoperative inflammation and IR. We, therefore, plan to undertake this proof of concept study to investigate:
1. The cellular pathways leading to postoperative inflammation/IR
2. Correlation between the magnitude of postoperative IR and body composition. These mechanisms are of importance given the increasing prevalence among surgical patients of sarcopenia (reduction in muscle mass) and obesity, and the associations between sarcopenia, obesity, inflammation and IR.
Ethics approval
National Research Ethics Service (NRES) Committee East Midlands Northampton First MREC approval date 15/08/2011, ref: 11/EM/0232
Study design
Randomised; Interventional; Design type: Process of Care
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Other
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Topic: Generic Health Relevance and Cross Cutting Themes; Subtopic: Generic Health Relevance (all Subtopics); Disease: Surgery
Intervention
Preoperative carbohydrate load, Single intervention: Preoperative carbohydrate loading using a commercially available preparation given to patients undergoing abdominal surgery. Participants will receive 2 servings of the drink on the evening before surgery and one serving on the morning of surgery. The drink will be compared to a placebo drink that will be administered in the same quantities and at the same times.
Study Entry : Registration and One or More Randomisations
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measures
Within subject differences in perioperative insulin sensitivity amongst obese, non-obese, carbohydrate loaded and non carbohydrate-loaded patients. Timepoint(s): End of study
Secondary outcome measures
1. The correlation between body composition and changes in perioperative insulin sensitivity
2. Differences in cytokine gene expression
3. Differences in muscle and fat genes and protein expression
4. The incidence of post-operative infectious and non-infectious complications
5. Differences between the groups in length of hospital stay
Overall trial start date
28/09/2011
Overall trial end date
28/09/2013
Reason abandoned
Eligibility
Participant inclusion criteria
1. Age 18-75 years
2. Correct body mass index (BMI) and waist circumference criteria (Obese group BMI >=30 or waist circumference > 94 cm in men and > 80 cm in women. Non obese group BMI 18.5-25) or
3. Waist circumference (<=94cm in men and <=80 cm in women)
4. Due to undergo elective major abdominal surgery
5. American Society of Anaesthesiologists physical status (ASA IIII)
6. Caucasian patients
7. Able to give informed consent and comply with study protocol
Target Gender: Male & Female; Upper Age Limit 75 years ; Lower Age Limit 18 years
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 32; UK Sample Size: 32
Participant exclusion criteria
1. History of significant preoperative weight loss (>10% over preceding 3 months )
2. Clinical history of pulmonary aspiration
3. Known gastrooesophageal reflux disease (GORD) or hiatus hernia
4. History of difficult intubation or conditions leading to the latter such as: previous neck radiotherapy/rheumatoid arthritis/presence of thyroid goitre
5. Metabolic disorders (e.g. diabetes mellitus, thyroid disease, Cushings Syndrome)
6. Simultaneous participation in another clinical study or involvement in a clinical study within the preceding 3 months
6. Patients with suspicion of alcohol/drug abuse
7. Pregnancy
Recruitment start date
28/09/2011
Recruitment end date
28/09/2013
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Queen's Medical Centre
Nottingham
NG7 2UH
United Kingdom
Funders
Funder type
Charity
Funder name
Core - The Digestive Disorders Foundation (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
European Society of Clinical Nutrition and Metabolism (ESPEN)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
National Institute for Health Research (NIHR) (UK) - Biomedical Research Unit
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary