ANZCTR search results

This is a phase 1a, single-centre, randomized, open label study to evaluate the safety, tolerability and pharmacokinetics of a single sublingual or oral dose of GDN-1 in adult healthy volunteers. There are 6 treatment arms.

Diabetes is a chronic non-communicable and slowly progressing metabolic disease often involving multiple pathological mechanisms. Multiple mechanisms underlie the pathogenesis of diabetes including subclinical inflammation, glucotoxicity and lipotoxicity. Elevated levels of inflammation, particularly in the adipose tissue, is believed to be the primary trigger preceded by all of the above mentioned pathological mechanisms. Recent scientific literature established a strong link between inflammation and diabetes highlighting the role of inflammation as a primary pathological trigger for development of diabetes and its complications. Current therapies in the diabetes are unidimensional, targeted only to ameliorate the hyperglycaemic conditions. To date little or no attention has been paid to design pharmaceutical strategies to delay or modulate inflammatory pathways involved in reducing insulin secretion and/or action. Moreover current anti-diabetic medications have persistent side effects, such as body weight gain and hypoglycaemia in patients on sulphonylureas and insulin; gastrointestinal problems with metformin and acarbose; weight gain and bone fractures with thiazolidinediones; genital or urinary tract infections predominantly in females with sodium glucose co-transporter inhibitors. In the light of increasing prevalence and health costs associated with diabetes and its complications, there is a necessity for development of easy to comply strategies to modulate multiple metabolic targets with excellent long-term safety profile. In search of these agents, some bioactive compounds (nutraceuticals) aiming at prevention of diabetes through anti-inflammatory mechanisms have shown promising results. Extensive research has been carried out on anti-inflammatory and anti-hyperglycaemic potential of curcumin. Also the long chain n-3PUFA have been shown to possess lipid-lowering and anti-inflammatory properties by modulating multiple metabolic targets. We propose to evaluate the complimentary and/or synergistic effects of curcumin and/or n-3PUFA on pro-inflammatory mediators and insulin sensitivity in people with pre-diabetes. This is a 2x2 factorial, randomized, double blind, placebo controlled study. Eligible participants will be asked to consume 4 caps daily; placebo, curucmin plus placebo, omega 3 fatty acids plus placebo, curucmin and omega 3 fatty acids combination, for 12 weeks. Participants will be donating blood on the first day and post intervention along with information on 3 day food consumption, physical activity and other medications.

The prevalence and impact of childhood overweight and obesity is increasing and is of growing concern to the wellbeing of Australian society. Scientific literature suggests that providing an incentive scheme may improve motivation and completion of behaviour change programs, but the potential of such schemes and their optimal delivery remain relatively unexplored in children. This project will be the first RCT internationally to test the effectiveness and implementation of an incentive scheme targeting behaviour change in children. Conducting a robust study testing the impact of incentive schemes in children may open up a whole new approach for managing a range of conditions that are directly associated with health-related behaviours.

Introduction Rheumatoid arthritis is a severe destructive inflammatory arthritis that affects 1.5% of the population. They have a 50% increased risk of cardiovascular events that is directly related to the disease process although the mechanisms of this remain unclear. New effective treatments for rheumatoid arthritis called the "Biologics" have become widely available over the last decade. This has resulted in dramatic improvements in the treatment of the arthritis. However, it remains unclear whether these treatments influence the risk of cardiovascular events. Pooled analyses of the large trials have not had sufficient power and are of insufficient duration to answer this question. Meta-analysis of the combined registry data found dramatic differences in the TNF-inhibitor treated group but these effects may be explained by confounding. Studies using assessments of pre-clinical vascular disease using imaging and physiological assessments of arterial stiffness seem more likely to show treatment effects but have thus far been inconclusive. Based upon studies in hypertension it is likely that studies utilising assessments of arterial stiffness and carotid artery wall thickness would require randomised controlled trials of considerable size and duration to detect treatment effects. Earlier pathological processes in vascular disease such as endothelial dysfunction are more likely to change quickly and detectably in response to treatment. However, studies have been inconclusive possibly due to the small sample sizes, insufficient study duration and because the studies evaluated subject with established and possibly irreversible disease. The Australian PBS funds Biologic drugs for patients with rheumatoid arthritis only after they have failed to respond to 6 months conventional DMARD therapy. This 6 month period presents an opportunity to evaluate the effects of TNF-inhibition (with adalimumab) upon vascular function in a randomised controlled trial while at the same time enhancing patient care. Our consortium have already conducted a small phase 2 study (Hunter HEART-RA has already evaluating the effect of adalimumab in anti-CCP antibody positive RA. This phase 2, single-centre, double-blind randomised, placebo-controlled study will evaluate the effects of adalimumab upon endothelial function anti-CCP positive and NEGATIVE rheumatoid arthritis. Methods 1. 36 subjects with Anti-CCP Positive Rheumatoid Arthritis and ; 2. 34 subjects with Anti-CCP Negative Rheumatoid Arthritis (age>18 years) Subjects within each group will be randomised 1:1 to receive adalimumab / placebo for 24 weeks in addition to "usual care”. During the 24-week trial subjects will undergo assessments of vascular function, rheumatoid arthritis disease activity, functional impairment and work disability. Assessments will occur at 0 (baseline), 12 and 24 weeks. The primary response variable will be peripheral endothelial function as measured by EndoPAT. Secondary response variable will include: 1. Arterial stiffness (Carotid-femoral pulse wave velocity, Central Aortic Augmentation Index as measured from the radial pulse wave analysis) 2. Carotid artery ultrasound (carotid initmal medial thickness, carotid plaque score and carotid wall elasticity) 3. Disease activity (ESR, CRP, joint counts, DAS28, SDAI) 4. Functional Ability (HAQ Questionnaire) 5. Work Disability (RA-WIS Questionnaire) 6. Australian Quality of Life (AQoL) Questionnaire 7. 40-joint musculoskeletal ultrasound.

The objective of CHAMPS is to perform a feasibility trial to determine whether treatment of common mental health problems in cardiovascular diseases (CVDs) is feasible by comparison to enhanced usual care (EUC). The treatment arm concerns cognitive-behavioural therapy, specifically a type of transdiagnostic treatment of common mental health problems known as the Unified Protocol (UP). The findings will establish an estimate of treatment effect size to inform a larger definitive RCT. We hypothesize that the CHAMPS intervention arm will reduce symptoms of anxiety, depression, stress, reduce the number of psychiatric disorders, improve quality of life and cardiac endpoints in comparison to EUC at six months post-baseline (post-treatment in the treatment). The study seeks to randomise 25 persons to each study arm transdiagnostic UP vs. EUC. The CHAMPS intervention arm will consist of 12 to 18 weeks transdiagnostic cognitive-behavioural therapy. The EUC arm will consist of information regarding depression in CVDs provided to patient and physician, in accordance with the National Heart Foundation of Australia's recommendations. A secondary objective of CHAMPS is to determine the incidence of emotional problems such as affective disorders in persons without mental health problems at baseline. Therefore a cohort of patients will also be recruited whom have no emotional distress at baseline, and this particular group will serve as a non-distressed control group in order to evaluate the incidence of mental health problems in CVD patients. This methodology is similar to recent depression RCTs in CVD populations. Importantly, the non-distressed control group will form a reference population to determine whether longer term emotional functioning and other aspects of CVD functioning in the UP and EUC groups is comparable to a group who were not-distressed during hospitalization for CVD.

Tears of the rotator cuff tendon are very common, causing significant pain and restricted movement of the arm, compromising patients’ daily activities, participation in sport and exercise, and ability to work. Exercise rehabilitation has previously been shown to be effective in improving pain, strength and quality of life scores in patients living with these tears, however when patients become symptomatic, and non-operative management inherently fails, they are typically repaired surgically. Post-operative rehabilitation is a critical part of the treatment following shoulder surgery. Specific exercises to improve mobility, strength and function of the shoulder are commonly prescribed after surgery, however debate and uncertainty currently exists regarding the amount of load permitted throughout the early post-operative stages and when and how to safely graduate this progressive loading stimulus. Improvements in surgical techniques have improved the possibility of an early or accelerated post-operative treatment protocol, yet a general consensus from specialists still does not exist. Understanding what happens in the muscle during rehabilitation exercises will allow health professionals to safely and effectively apply a rehabilitation program after injury or surgery. This study will explore EMG activation and perceived loading of rotator cuff and shoulder girdle musculature in healthy participants during rehabilitation exercises commonly prescribed to patients after injury or early post-surgery. The implications from these studies will advance the clinical knowledge and practical application of exercise rehabilitation after rotator cuff injury or surgery to enhance patient outcomes and improve overall function.

tDCS involves the application of a very weak electrical current to the scalp, which acts to modulate the excitability of underlying cortical neurons, thereby altering their function. tDCS is both safe and painless, and can induce changes in brain function which are measurable for over an hour after the cessation of stimulation. In order for tDCS to be optimally utilised, however, research which directly compares different stimulation parameters is greatly needed. To date, several studies have demonstrated the capacity for tDCS to enhance performance during working memory (WM) tasks when it is applied over prefrontal brain regions (e.g., DLPFC). However, despite encouraging initial results, tDCS has thus far only been able to produce modest levels of cognitive enhancement in healthy individuals. One way of potentially improving the effectiveness of this technique would be to apply it concurrently over a combination of brain regions known to be involved in WM. Therefore, this project specifically aims to compare the effects of tDCS delivered over either the left DLPFC alone, or the left DLPFC in combination with the left parietal lobe. Simultaneous stimulation of prefrontal and parietal brain regions will be achieved using a multifocal ‘high-definition’ stimulation montage which allows for accurate stimulation of two independent cortical targets. The parietal brain region was chosen as the additional stimulation site due to its known involvement in WM. Both behavioural (WM performance) and neurophysiological (EEG, TMS-EEG) data will be utilised to assess the effectiveness of this technique.

The study will evaluate the deliverability and efficacy of Ibrutinib-R-mini-CHOP chemotherapy in elderly patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Who is it for? You may be eligible to join this study if you are aged 75 years or above and have been newly diagnosed with DLBCL for which you have received no prior treatment (excluding prednisone). Study details All participants in this study will be treated with a chemotherapy regime known as Ibrutinib-R-mini-CHOP. This will include treatment with the drugs prednisone (orally), ibrutinib (orally), rituximab intravenously ((IV) - i.e. administered directly into the vein), cyclophosphamide IV, doxorubicin IV, vincristine IV and Pegfilgrastim G-CSF (subcutaneous injection). Treatment duration will be for up to 8 x 28 day cycles as tolerated. All participants will be regularly assessed for a minimum of 2 years in order to evaluate the safety, toxicity and effectiveness of treatment.

The aim of this trial is to compare current patella component designs (inset vs onlay), with the hope of finding significant improvement in anterior knee pain or knee function for one design over the other. Subsequently, future patients can benefit from surgery using the superior design. This trial will recruit suitable and consenting participants from the private rooms of Prof. D Wood at the Perth Orthopaedic Institute, HPH. Consenting participants would undergo a total knee arthroplasty (which they otherwise would undergo, whether they were enrolled in this study or not, as part of their clinical care). The patella component of their total knee arthroplasty (TKA) will be randomised to either an inset design or onlay design. All surgeries will be carried out by Prof. D Wood using his routine surgical technique and peri-operative care. Participants are not placed at increased risk or offered inferior treatment in this study based on current knowledge. Participants will have standard postoperative weekly physiotherapy sessions as part of the standard care following total knee arthroplasty, and will be followed up by Prof Wood at 3, 6, 12, 24 and 60 months, also as part of usual care. During this interval follow up, participants will also complete a series of validated scoring questionnaires and functional tests, administered by a trained assessor. These functional data will be compared across the two study groups (inset patella component, onlay patella component) and hazard ratios and confidence intervals generated using statistical software. Anonymous results will be submitted for publication in a leading orthopaedic journal to inform other surgeons and medical professionals of the results.

The primary aim of this project is to investigate the effectiveness of combined trauma-focused CBT and exercise to decrease pain and disability of individuals with chronic whiplash and PTSD. The secondary aims are to investigate the effectiveness of combined trauma-focused CBT and exercise to decrease posttraumatic stress symptoms, anxiety and depression, and to investigate the effectiveness of trauma-focused CBT alone on posttraumatic stress symptoms and pain/disability. For individuals with chronic whiplash and posttraumatic stress, it is hypothesised that: 1. Trauma-focused CBT followed by a physiotherapy exercise program will result in significantly greater improvements in pain and disability up to 12 months post treatment compared with supported counselling followed by a physiotherapy exercise program. 2. Trauma-focused CBT followed by a physiotherapy exercise program will result in significantly greater improvements in posttraumatic stress symptoms, anxiety and depression up to 12months post treatment compared with supported counselling and a physiotherapy exercise program. 3. An initial treatment of trauma-focused CBT will result in significantly greater improvements in pain/disability, posttraumatic stress symptoms, anxiety and depression immediately post-treatment compared with a supported counselling intervention.