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Asthma affects approximately 1:10 adults and 1:5 children. Although most subjects attained good control of their asthma with conventional treatment, there is a significant proportion who are resistant to conventional treatment and remain uncontrolled. Although there are several mechanisms that may explain incomplete asthma control, one important factor which is potentially easy to address, is the presence of severe small airways disease that is not effectively improved by inhaled corticosteroid treatment. The small airways are an important determinant of asthma control and severity. They are airways with an internal diameter of 2 mm or less and because of the branching nature of the airway tree, occupy a very large surface area compared to the larger and more proximal airways. We have recently shown that small airway function improves with high dose inhaled corticosteroid treatment in parallel with improving asthma control. Furthermore, asthma control and severity are strongly related to small airways function. It therefore follows that persisting small airways disease is an important determinant of severe asthma and that better treatment of the small airways will improve the treatment of severe asthma. The obvious problem with treating small airways that are severely affected by inflammation and tissue remodelling, is that it is difficult to deposit therapeutic aerosols there. This is because ventilation to those airways is poor, because of severe airway narrowing and closure. Therapeutic aerosols require ventilation to carry them to the target sites and so the worst affected airways receive less of the inhaled aerosols. There is a theoretical advantage of using fine particle aerosols, because they are more likely to be carried to areas where ventilation is poor. Particles greater than 3 – 5 um deposit in the medium to large airways, while smaller particles will be carried into smaller and narrowed airways. Therefore, we propose that small particle aerosols will be more effective in uncontrolled asthma than larger particle aerosols.

Cardiopulmonary bypass (CPB) is commonly used in cardiac surgery to maintain blood flow to the brain. However, loss of pulse pressure during CPB means that brain blood flow may be low and brain oxygen levels may fall. This may be bad and affect brain performance after surgery. Oxygen levels in the brain can be monitored with Near Infrared Spectroscopy (NIRS) and brain performance can be assessed with psychological tests. One way to improve brain blood flow and oxygen levels may be to target a slightly higher carbon dioxide (CO2) concentration in the blood during and after CPB. This is because even a slight increase in CO2 can open up the blood vessels to the brain, increase blood flow to it and increase oxygen levels for brain cells. However, targeting such slightly higher CO2 levels in this setting has not been formally studied. The aim of this study is to compare the changes in cerebral oxygen levels (SctO2) and psychological test-assessed brain performance when a mildly increased CO2 level is targeted compared with a normal CO2 level during and after CPB. We plan to study forty adult patients having CPB (twenty targeting normal CO2 levels and twenty targeting mildly increased CO2 levels), and to measure their SctO2 and psychological test performance prior to surgery and before hospital discharge. The information derived from our investigation will be used by doctors to improve oxygen levels in the brain of patients during and after CPB in the future.

The aim of this research is to test if participant retention in a commercially available meal replacement program (MRP; Impromy) is improved when the standard Impromy program is modified to enhance weight loss. Enhanced weight loss will be expected by incorporating 3 days per week of ‘additional calorie restriction’ and one day of ‘free eating’ per week, over 16 weeks. Impromy is a weight loss program developed in partnership with CSIRO, and validated by CSIRO. It is commercially available through pharmacies across Australia. The current program consists of an energy restricted weight loss diet that includes meal replacements, personalised support from trained pharmacy assistants and a phone application for additional support and monitoring. The outcomes of this study will inform development of the Impromy program with the goal of improving program retention and therefore overall weight loss. A second aim of this study is to investigate how the two dietary protocols affect , or are affected by: 1.Biological indicators of health, including changes in body fat and muscle, blood glucose and cholesterol levels, blood pressure, nutrient status, gut health and the gut bacteria, genetic & blood and buccal cell epigenetic markers and novel markers of metabolic health (including retinal vascularity). 2.Eating behaviours and food craving, well being, psychological outcomes, perceived health, cognitive function and gut comfort.

Activity pacing is an occupational therapy rehabilitation intervention commonly used with older adults who have deconditioned during an acute hospital admission. Activity pacing involves teaching people different techniques to regulate their level of activity and how they do their daily tasks. Activity pacing and energy conservation have been shown to have some effect with persistent pain populations and in people with chronic disease. Yet there is currently no evidence for use with the deconditioned older adult. For the purpose of this research, activity pacing will include seven activity pacing techniques - 1. Use self-monitoring to listening to your body 2. Use short regular rests during the day and during activities 3. Find a sustainable baseline and then gradually increase activity 4. Break tasks into manageable parts 5. Plan tasks and set goals 6. Alternate high energy tasks with low energy tasks 7. Prioritise tasks and delegate where able The aim of this study will be to evaluate the effectiveness of activity pacing with deconditioned older adults on their participation in everyday tasks. This will be done by comparing two groups- 1) occupational therapy rehabilitation with activity pacing, 2) occupational therapy rehabilitation with no activity pacing. A secondary aim will be to compare the effects of the two interventions on quality of life and well-being, knowledge of activity pacing techniques and symptom management (pain, fatigue and self-efficacy). Deconditioned older adults who are admitted to a private hospital from the acute setting will be invited to participate. A randomised controlled method will be used to compare the effectiveness of occupational therapy rehabilitation with activity pacing and occupational therapy rehabilitation with no activity pacing. The activity pacing intervention will be multi-faceted with individual sessions, group education, written handouts and a practical group allowing practice of the above activity pacing techniques. To ensure the second group (occupational therapy with no activity pacing) are not disadvantaged, patients will receive modified activity pacing education (two individual sessions- one education and one practical, written handouts) 2 days prior to discharge and after the completion of outcome measures.

When chronic kidney disease patients on dialysis have low calcium due to low vitamin D activity, calcitriol is the standard therapy used. However, it is costly and more likely to cause side effects of high calcium and high phosphate. On the other hand, cholecalciferol is cheaper with possibly less side effects on calcium and phosphate. The purpose of this study is to compare cholecalciferol to calcitriol as vitamin D therapy in patients with chronic kidney disease who are on dialysis. We will change study participants who are on calcitriol to cholecalciferol, and examine cholecalciferol’s effectiveness through its effects on blood results over 12 weeks. During recruitment, participants' age, gender, ethnicity, weight and height, smoking status, existing vitamin D therapy, kidney disease, time on dialysis, other medical conditions, dialysate calcium concentration, phosphate binders, and previous blood results will be obtained from them personally or through medical record. Baseline blood tests will be performed to analyze detailed components of the calcium and vitamin D metabolism systems. If they meet the inclusion criteria, their calcitriol therapy will be changed over to cholecalciferol. Further 3 sets of blood tests will be done at 4-week, 8-week, and 12-week period to monitor treatment effects and determine need for therapy adjustment. We would estimate the proportion of patients on maintenance calcitriol who can be changed successfully to cholecalciferol therapy. We hypothesize that the use of cholecalciferol for maintenance therapy in adult chronic kidney disease patients on dialysis is comparable to the use of calcitriol, as shown by successful change from calcitriol to cholecalciferol therapy in a worthwhile proportion of patients.

This pilot randomised controlled trial will be the first to investigate if supervised progressive resistance training (strength training) is safe and feasible for adolescents and young adults with Prader Willi syndrome aged 13-39 years. It will also investigate the effect of the training on body composition (including muscle mass), muscle strength, muscle performance, and physical activity. Twenty-two adolescents and young adults with Prader Willi syndrome will be recruited through the Prader Willi Syndrome Association of Victoria and through the Prader Willi Syndrome register. Participants will be randomly allocated to either a 10-week twice a week community gymnasium based progressive resistance training program supervised by a physiotherapist (n=11) or a waitlisted control group (n=11). The training program will comprise 7 exercises on pin-loaded weight machines: 3exercises for the arms, 3 exercises for the legs and 1 exercise for the trunk which will take 45-60 minutes to complete each session. Participants will be assessed before they start the intervention and again after they complete the intervention.

A profusion of imaging and lesion based research now indicates that the dorsolateral prefrontal cortex (DLPFC) is a vital substrate for a number of important cognitive functions, particularly working memory (WM). Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique which applies a very weak current to the scalp which can transiently alter underlying brain function as well as behaviour. When applied over the DLPFC, tDCS has been shown to both enhance WM performance in healthy individuals and ameliorate its dysfunction in clinical cohorts. These changes are hypothesised to be due the ability for tDCS to alter the excitability of neurons within the brain, which in tern leads to neuroplasticity-related changes in cognitive function. Nevertheless, to date, the level with which tDCS can modulate cognition remains relatively modest and, as such, research is needed to explore ways of improving the clinical efficacy of this technology. There is currently some limited evidence to suggest that combining tDCS delivery with a cognitive task may have a synergistic effect, leading to greater subsequent improvements in cognition. However, this finding has yet to be systematically explored. The current project, therefore, aims to investigate this potential task-dependency effect in detail in a cohort of healthy adult participants utilising both behavioural and neurophysiological outcome measures.

To quantify inspiratory muscle endurance, through the Fatigue Resistance Index method, in healthy people. Poor respiratory muscle endurance is a consequence of invasive mechanical ventilation for patients in intensive care (1,2). Over the past 10 years, researchers including ourselves (2,3) have used the ‘Fatigue Resistance Index’ (FRI) method to quantify the endurance of the respiratory muscles of intensive care patients. This involves inhaling through a hand-held device for 2 seconds, then breathing against resistance for 2 minutes, and then inhaling maximally through the hand-held device again. The FRI is a feasible alternative to more complex invasive methods of analysing diaphragmatic endurance. However, to our knowledge, this method of quantifying endurance has not been tested in a normal population. Following our publication in 2015 (1), we wish to measure FRI in normal healthy subjects to allow us to compare our data from intensive care patients with age and gender matched healthy participants. REFERENCES: 1. Bissett B, Ledtischke IA, Boots R & Paratz J. Weaned but weary: one third of adult intensive care patients mechanically ventilated for 7 days or more have impaired inspiratory muscle endurance after successful weaning. Heart and Lung. 2015; 44: 15 – 20. 2. Chang AT, Boots RJ, Brown MG, Paratz J, Hodges PW. Reduced inspiratory muscle endurance following successful weaning from prolonged mechanical ventilation. Chest. 2005; 128: 553 – 559. 3. Bissett BM, Leditschke IA, Paratz JD, Boots RJ. Protocol: inspiratory muscle training for promoting recovery and outcomes in ventilated patients (IMPROVe): a randomised controlled trial. BMJ Open. 2012:2e000813.

What is this study about? The purpose of this study is to investigate how safe and tolerable repeat doses (applied daily for 7 days) of ZYN002 transdermal gel is in healthy volunteers and patients with epilepsy. The study will look at how the body absorbs, distributes, breaks down and then removes the study drug from your body. This will be done by analysing the levels of ZYN002 in your blood and urine at various times following drug administration. Your skin at the application sites and your hands will be checked to see if there is any irritation or reactions present after ZYN002 application. The study will also investigate neuropsychological effects that ZYN002 may have by administering a number of neuropsychological tests. Who is if for? You may be eligible to join this study if you are aged between 18 and 55 years and are either in general good health or have epilepsy with partial onset seizures that is stable. Study details: This study will investigate various doses of ZYN002 compared to a placebo gel (a treatment with no active ingredients which looks like the real thing but it is not). This study is ‘double-blind’ which means you and your study doctor, together with the study staff administering the study treatment will not know whether you are receiving ZYN002 or placebo gel. What does study participation involve? Your participation in the study includes A screening visit, which could be up to 28 days before your study treatment. One confinement period starting on the evening before dosing and lasting until 36 hours after the last study treatment on the 8th study day. This will require eight (8) nights in the clinic. Two out-patient clinic visits following the confinement period on Days 9, Day 10, Day 11 and the End of Study Visit on Day 13. These visits will be at 48, 72, 96, 72 and 144 hours after the last application of the study treatment on Day 7. Additional out-patient visits may be required if there is any skin irritation present at the study treatment application sites. Throughout the study you will have various medical tests (physical examinations, vital signs measured, ECG measured, neuropsychological tests) and will have several blood and urine samples collected for laboratory analysis.

Cannabis is the most widely used illicit drug and is associated with considerable health related morbidity. About 1 in 10 cannabis users become dependent on the drug leading to high-level of treatment seeking. There is increasing interest in the idea that severe cannabis dependence might be effectively treated by substituting smoked cannabis for a safer, more benign cannabinoid agonist medication. Recent laboratory studies suggest this approach holds promise as an effective therapy in dependent users. Our team has recently published the first ever-clinical trial of the cannabinoid agonist medication Sativex in alleviating cannabis withdrawal. This world first study demonstrated the safety and efficacy of Sativex relative to Placebo in an inpatient setting. This project proposed the first ever outpatient randomised controlled trial (RCT) to test the efficacy, safety and cost effectives of Sativex for treating cannabis dependence the community. Sativex will be given to severely cannabis dependant patients who have not previously responded to conventional treatment. Subjects (n=142) will be randomly allocated to a 12-week course of Sativex or placebo, with standard counselling and clinical reviews across both groups, and a 12-week follow up after the completion of maintenance dosing. This proposal presents an exciting innovation in the embryonic field of clinical research into the world’s most prevalent illicit drug. As well as examining the efficacy of this medication, the trial will address a range of issues important in any future translation of Sativex use into routine clinical practice. The development of an effective medication for treating cannabis dependence would have wide reaching clinical and public health benefits.