Current Research Studies

The following are summaries of some of the research studies within CORE which are being planned, currently being conducted or have just been completed and are being published.

 Randomised Controlled Trials (RCT's)

RCTs are the coin of the realm. They are the most important methods for clinical research to uncover new information in a scientific robust manner. The Australian healthcare system provides an environment that is conducive to running clinical trials with a high quality medical system, good training in scientific method, a vigorous but supportive human ethics approval process and a population who are generally pleased to act as participants. Through CORE we have conducted several RCTs to date. Two of these have become landmark studies in the medical literature - The BMI 30-35 trial, the first to compare medical and surgical treatment for obesity, and the Diabetes trial, another comparison of the best medical and surgical treatments for this particular group. We have a number of RCTS ongoing or about to begin.

The Adolescent RCT

We admitted 50 severely obese adolescents, randomised them to best non-surgical care of their obesity or LAGB placement. The 2 year follow up is complete and the primary report of the study is about to be submitted. Adolescent obesity is now seen as a major health problem across the world.

The Obstructive Sleep Apnoea RCT

A randomised controlled trial of the effect of substantial weight loss on obstructive sleep apnoea. This study has been enrolling patients for 2 years and we have almost finished recruiting the 60 participants needed for the study. We will then have a two year period to complete follow up.

The Diabetes BMI 25-30 RCT.

50 participants have an optimal program of diabetes care and half will be randomised to substantial weight loss using the LAGB procedure. Comparison of outcomes will be made at 12 months after randomisation to compare remission rates and at 5 years to compare durability of effect.

The "Lifestyle" Series of RCTs

Optimization of the outcomes after LAGB is dependent not only on safe and correct surgical placement but also requires leading the patient through a permanent lifestyle change characterized by optimal eating, maximal acceptable exercise and activity and an appropriate pattern of clinic visits and adjustments. We need to determine exactly what is optimal and to do that we have constructed a series of RCTs which will guide us. The first of these, testing an intensive exercise and daily activity program against the routine advice and support which we have traditionally provided has commenced. The second will look at three different approaches to eating after the LAGB. The third will compare the relative effectiveness of liquid versus solid food diet. The final study will measure the relationship between clinic visits and adjustments and outcomes. All of these studies are part of the PhD studies of Kristine Egberts.

Other Clinical Studies

Not all questions can or need be answered by RCTs. With a large and well managed database containing many thousands of people with obesity who are losing or have lost weight. For various significant questions we draw on observational studies. The most significant of these is the prospective study of the metabolic syndrome and the study of the LAGB in the Indigenous people with diabetes.

Metabolic Syndrome

The metabolic syndrome is a collection of features each of which is an important risk factor for cardiovascular disease. This research project addresses the challenge of obesity control and its relationship to changes in the metabolic syndrome. This study is just commencing and in it we seek to improve our understanding of how much weight loss is required to achieve a significant improvement in the features of metabolic syndrome, and in which order these features resolve. We also seeks to better define the changes in gut hormones and adipokines that may underpin the improvement in the metabolic syndrome. With this knowledge, optimal treatments for metabolic syndrome, and realistic weight goals for our patients, may be defined. We will perform a linear prospective observational study of 200 obese people with the metabolic syndrome who have weight loss after LAGB.

Indigenous Diabetes study

We have shown clearly that weight loss will lead to a high rate of resolution of type 2 diabetes in an ideal Caucasian population. However diabetes is a common and severe disease for the Indigenous people. In this study we will test if the LAGB approach to treating this problem is an acceptable option for the Indigenous people and if they will be able to follow the compliance needs to achieve a good result. We plan to seek a total of 30 people living in the region of Shepparton and attending the Rumbalara Health Service. We need to understand of the important cultural differences which exist with sensitivity to the socio-cultural profile which emphasizes the links between the person, the family and the community and establishes close collaboration with the communities, sharing ownership and decision making. The approach to illness and treatments is modified by these cultural differences with issues of communication, understanding and trust influencing behaviour.

The Survival study

We have compared the survival of our patients with a group of similar obese people in Melbourne who have not lost weight and have shown a very important survival advantage to those in the weight loss group. We are now working with international groups who have conducted similar studies with the plan of pooling our data and thereby achieving enough numbers to ask more detailed questions about which patients in particular are more likely to benefit.

Intensive Care study

This is a study of failure. No treatment is always successful, no less the LAGB procedure. We have identified those who have failed to lose enough weight (less than 25% of their excess weight at 2 years) and we are establishing the optimal approach to understanding why they have failed and measuring the effectiveness of more active attempts to improve their outcomes. How many can we salvage? What criteria predict a worthwhile outcome? Who will continue to fail? The study involves an intensive analysis of why failure occurred and an intensive attempt to correct the problems.

Knee Pain Study

The weight bearing joints carry an added load in the severely obese and degenerative disease is common. This study involves a clinical and radiological evaluation of the knees of symptomatic patients before, and two years after LAP-BAND® placement. Approximately 60 subjects have been followed. The X-rays of the knees are now being evaluated blindly and a report of this study should be available during 2008.

Psychological Assessment Study

Is psychological assessment prior to weight loss surgery a worthwhile process? We are performing a detailed and comprehensive psychological assessment on 200 patients using a semi-structured psychological interview known as the SCID (Structured Clinical Interview for DSM-IV Disorders) and a series of questionnaires. From these we hope to determine the prevalence, nature and severity of clinical psychological disorders and personality disorders. We also plan to investigate the validity and reliability of the Beck Depression Inventory (BDI) in obese individuals by concurrently administering the BDI and the SCID. We hope to find possible predictors of good and poor weight loss outcomes and compliance at after surgery and to observe the effect of weight loss on DSM-IV diagnosis, mood, eating behaviours and cognitive style.

Technical Studies of the Lap-Band ® Procedure

Measuring the physiology and pathophysiology of the upper stomach and distal oesophagus.

We are defining the physiology critical to success with the LAGB in terms of esophageal motility and pressure topography, oesophageal and gastric compliance, bolus transit and the mode and threshold for the generation of peripheral gastric mediated satiation. We wish to determine the physiological effects on the above parameters of adjusting the volume within the LAGB and correlate these with sensations of satiety. We also hope to identify the pathophysiological features associated with inadequate weight loss, adverse symptoms and proximal gastric enlargement following LAGB and evaluate these pathophysiological features as predictors of outcome with primary and revisional surgery. At the same time we are developing and validating a technique of high resolution video manometry as a diagnostic test for LAGB patients and establishing the relationship of gastric emptying above and below the LAGB to satiation, symptoms and weight loss

Satiety - Brain Imaging II Study

Satiety is the key to effectiveness after LAGB placement. The better we understand the mechanisms and pathways for satiety, the better we can optimize the patient care process. In association with collaborators at the Florey Institute we are using functional magnetic resonance imaging (fMRI) of the brain in successful band patients before and after meals to identify the centres at the brain stem and hypothalamus activated by this stimulus.

Systematic Reviews of the literature

There is a wealth of information hidden within the mountains of published but unsorted data. Systematic review seeks to find the nuggets of gold within the mountain. The following systematic reviews are in preparation:

Anaesthesia and the Lap-Band - A Systematic Review

We are trying to define from the medical literature the steps that should be taken prior to anaesthesia to minimize problems with aspiration.

Exercise and activity after LAGB - A Systematic Review

In support of the RCT described above, we will review the existing literature to identify the existing findings.

Eating patterns and content after LAGB - A Systematic Review.

What do we already know? We plan to review this and bring the key findings together before embarking on the RCT

Erosions after Lap-Band Surgery - A Systematic Review

Erosions are an uncommon but concerning complication of LAGB placement. As a support for the study of erosions which have been managed by the surgeons associated with CORE, we are examining the literature.

Technical studies of the co-morbidities of obesity

Cardiac Study

Numerous unfavourable changes occur to the heart in obesity. We have been evaluating cardiac structure and function in the morbidly obese using MRI and Echocardiography. We have now measured the change in cardiac structure and function in association with substantial weight loss. We hypothesize that, in obese patients, significant weight loss will improve accepted parameters of cardiac function and cardio-vascular risk profile.

Cardiac Liver Study

Non-alcoholic steatohepatitis (NASH) is a common and potentially dangerous condition in the severely obese. Its diagnosis rests on accurate measure of liver fibrosis. There is a strong need for an accurate method of measuring liver fibrosis without resorting to liver biopsy. Techniques of measuring cardiac fibrosis using MRI have been developed . We are testing if these methods can be validated for liver fibrosis.

Adipose Tissue Study

Animal studies suggest that adipose inflammation centred on macrophages is a link between obesity and metabolic syndrome. Two macrophage population appear to exist. In the lean, solitary ‘resident' macrophages predominate. Obesity, on the other hand, is associated with ‘crown' macrophages that surround necrotic adipocytes. We are seeking and understanding of how these contribute to the inflammation of obesity and to insulin resistance.

Cost-effectiveness evaluations

The identification and characterization of safe and effective treatments are no longer sufficient. We must also evaluate the cost of the different options. The randomised controlled trials each have involved the collection of cost data and a comparison of the cost-effectiveness of the two arms of each study can be performed. We have just completed and published the measurements of cost-efficacy and costeffectiveness for the Diabetes RCT. Data from the adolescent RCT are available for analysis and data for the obstructive sleep apnoea are being collected.