ANZCTR search results

Placebo-controlled, First-In-Human study assessing the safety and tolerability of PRN1008 in healthy volunteers. Participants will be randomised to receive a single oral dose of PRN1008 or a single oral dose of placebo. Up to four cohorts of eligible participants will be studied.

Examine the effect of twice daily administration of 150mg ivacaftor on exocrine pancreatic function of patients with cystic fibrosis and at least one copy of the G551D CFTR mutation

We will evaluate whether Rasagiline is an effective treatment to alleviate symptoms of freezing of gait (FOG) in Parkinson’s disease. 40 patients with FOG will be randomised to either Rasagiline or placebo arms. Treatment response will be assessed by video recordings and accelerometry of specific walking tasks (Timed up and Go test), taken before and after the intervention. In addition, functional brain imaging whilst patients perform a validated virtual reality gait paradigm will be used to determine the brain activation patterns associated with improvements in FOG. The use of brain imaging will also allow us to see why patients might have differential responses to therapy. Identifying the nature of these relationships will hopefully advance our understanding of freezing.

Pneumonia in children is a worldwide problem and a leading cause of morbidity and mortality. Rarely pneumonia is complicated by an ‘empyema’ where fluid collects around the lung and requires drainage with a tube. Many different types of bacteria can cause pneumonia and empyema. Streptococcus pneumoniae (SP) is one of the leading causes and has more than 90 different strains. It is unknown why some children are susceptible to pneumonia from SP; some evidence from adult patients suggests that there may be a genetic reason for susceptibility to Pneumococcal infection. Furthermore, viruses are commonly found in the upper airway of children with pneumonia and increase the risk of infection with SP. Vaccination can help prevent infection with many of the strains of pneumococcus. Australia recently introduced a vaccine which covers 13 of these strains. The main aim of this study is to look at the effectiveness of this newly introduced vaccine. The study will also look at the other bacteria and viruses that can cause pneumonia in children in Australia using sensitive molecular tests.

The current study aims to provide nursing staff in aged care residential facilities with a psychologically-based mobile application in conjunction with a web-based system. The Nurses Behavioural Assistant (NBA) will provide evidence based interventions to assist nursing staff to implement effective non pharmacological behavioural intervention strategies in response to behavioural and psychological symptoms of dementia (BPSD) in real time. Through educating nursing staff via the NBA it is anticipated that they will have more management strategies to draw from and feel more competent when responding. As a consequence, the residents may experience an improved quality of life and may show a decrease in the number behavioural and psychological symptoms experienced. The current research will be conducted at an aged care residential facility which houses 30 residents, with approximately 30 personal care attendants and nursing staff. Nursing staff and personal care attendants will be provided with an initial NBA training session, and then asked to use the NBA application over a 4 week period. Data on the BPSD each resident experiences and the interventions used will be inputted via the NBA mobile application and then automatically transferred to a secure server. Data will also be viewable to nurses via the web-dashboard. This data will be used to measure the NBA uptake, as well as the effectiveness of the behavioural management strategies recommended. Residents will be assessed on their level of dementia, anxiety, depression, confusion and agitation. Nursing staff will be assessed on their level of knowledge regarding BPSD, before and after the intervention. Nursing staff will also be interviewed to provide feedback regarding the implementation of the NBA at the end of the research. The results will provide a theoretical and applied basis for future expansion of the NBA system to other aged care facilities

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities characterised by dysglycemia, raised blood pressure, elevated triglyceride concentration, low high density lipoprotein (HDL) cholesterol level and obesity (central adiposity) (Alberti et al., 2009). In Australia, up to approximately one third of the population is diagnosed with metabolic syndrome (Cameron, Magliano, Zimmet, Welborn, & Shaw, 2007). These numbers are only expected to increase in the coming years. The most unifying concept of metabolic syndrome is insulin resistance (Bremer, Mietus-Snyder, & Lustig, 2012). There is ample evidence suggesting altered lipoprotein homeostasis in insulin resistant state (Avramoglu, Basciano, & Adeli, 2006). Chylomicrons are lipoprotein particles that transport dietary fat from the intestine to tissues expressing lipoprotein lipase (LPL) such as skeletal muscle and adipose tissue. In insulin resistance, chylomicron homeostasis is impaired: either due to overproduction and/or delayed removal of chylomicron particles from circulation. The balance between chylomicron production and remnant clearance will determine the exposure of arterial tissues to pro-atherogenic remnants. In the fasting state, the circulating concentration of chylomicron particles is elevated in insulin resistance compared to normal controls (Curtin et al., 1996). Following a lipid-rich meal these defects are further manifested with elevated concentrations of chylomicrons persisting in circulation for a longer time compared to insulin sensitive controls (Avramoglu et al., 2006). As humans spend most of their lives in a postprandial state due to ingestion of several meals eaten in sequence, these insulin resistant subjects would be placed at greater risk of developing atherosclerosis, particularly if remnant (small, lipid-poor) chylomicron particles accumulate. Very little is known about the distribution profile of the chylomicron remnant fractions in the postprandial state, though it has been shown that these smaller particles have greater atherogenicity (Nakajima et al., 2010; Nakajima et al., 2011; Nakajima et al., 2012; Pang, Chan, Barrett, & Watts, 2012). The overarching aims of this project is to determine whether subjects with metabolic syndrome exhibit a more atherogenic size distribution of chylomicron particles than control subjects in the fasting and postprandial states. Furthermore, since dietary modification is an important supportive therapy for diabetes, metabolic syndrome and CVD, one aspect that may be important is the fatty acid composition of a meal. There is some evidence that dietary fatty acid composition may affect chylomicron homeostasis and fat oxidation rate (DeLany, Windhauser, Champagne, & Bray, 2000; Perez-Martinez et al., 2011; Silva et al., 2003). Thus this study will also investigate the effect of meals containing a range of vegetable oils each with differing fatty acids on the postprandial size distribution of chylomicron particles. Of particular interest is the effect of an edible oil, rice bran oil, that has been shown to have beneficial effects on cholesterol and hepatic lipoprotein concentration (Lai, Chen, Chen, Chang, & Cheng, 2012; Most, Tulley, Morales, & Lefevre, 2005).

This study assesses if patients who are suitable for a transplant (and have a suitable bone marrow donor) will have better results if they are treated with a transplant compared to those patients that would have had a transplant but a suitable bone marrow donor was not available and instead received standard chemotherapy. The trial results will show whether future treatment of AML in patients over 50 should always include BMT whenever possible. Who is it for? You may be eligible to join this study if you are aged between 51 and 70 years of age (inclusive), diagnosed with Acute Myeloid Leukaemia (AML) of intermediate or poor prognosis, have achieved first complete remission (CR1) or complete remission with incomplete blood count recovery (CRi), have an indication for reduced intensity conditioning transplantation (RICT) but not myeloablative allogeneic hematopoietic stem cell transplantation (Allo SCT), judged to be able to tolerate further standard consolidation chemotherapy, willing to undergo a RICT if a suitable donor is found, and willing and able to comply with protocol requirements. Trial details Participants in this study will be divided into one of two groups – one group are those who will receive Reduced Intensity Conditioning Transplant (RICT) as an available suitable bone marrow donor (i.e. Matched Sibling Donor (MSD) or Matched Unrelated Donor (MLD)) has been found whilst the other group is comprised of participants will not undergo RICT as a suitable bone marrow donor was not available. Participants in the group that will undergo RICT will proceed as soon as possible to transplant as the next treatment after achieved remission. Due to medical or logistic factors, consolidation course(s) according to institutional practice may be given. Consequently, patients in the RICT group will (before conditioning) receive a total of 1-3 chemotherapy courses. If a patient in the RICT group relapses, or if a contraindication to the assigned treatment occurs, the patient will be treated at the discretion of the clinician. Centres may select any of the following conditioning regimens and are then asked to consistently use the chosen regimen. 1) Intrathecally administered methotrexate will be given to selected patients as per centre routine. As fludarabine is metabolized partly by a renal mechanism (Malspies Sem Oncol 1990), doses of fludarabine need to be modified if the calculated or assessed renal clearance is below the lower limit of the normal range. 2) Busulphan (administered orally or intravenously (IV)) and fludarabine. Fludarabine 30 mg/sqm IV infusion over 30 minutes on day –8 to day – 4 (=five days) for MSDs and on day -9 to day -5 or -4 (= five or six days) for MUDs. Busulphan may be administrated orally or intravenously. Oral busulphan will be administered as a total dose of 8 mg/kg, given as eight doses of 1 mg/kg each on day –4 (two doses), day –3 (four doses) and day –2 (two doses). Intravenous busulphan will be administered with a total dose of 6.4 mg/kg Busulphex (Registered Trademark) given as two doses of 3.2 mg/kg each, administered over 3 hours, on days -3 and -2. In-vivo T depletion with ATG, or alemtuzumab, as per local standards is permitted for MUDs. There shall be an interval of 8 hours between fludarabine and busulphan, and 48 hours between last dose of busulphan and infusion of stem cells. SUPPORTIVE MEASURES POST TRANSPLANT: Supportive measures post-transplant listed below represent basic general recommendations. In principle, centres are free to follow their local standard guidelines including blood transfusion support, antibacterial prophylaxis, herpes simplex virusand varicella zoster prophylaxis, surveillance and pre-emptive treatment of Cytomegalovirus (CMV). , fungal prophylaxis, P. carinii prophylaxis, and the use of Granulocyte colony-stimulating factor (G-CSF) in the post-transplant setting should be individualized. IMMUNOSUPRESSIVE THERAPY: Immunosuppressive therapy in the RICT setting includes the use of eithermethotrexate or mycophenolate mofetil (MMF) in addition to cyclosporine-A (CyA) in this trial. The dose of CyA should be targeted and adjusted to a serum concentration as per center preference. The first doses of CyA are given intravenously to try and ensure adequate levels at the time of transplant. If there is nausea and vomiting anytime during CyA treatment the drug should be given intravenously at the appropriate dose. Blood pressure, renal function tests (creatinine, BUN), electrolytes and magnesium need to be followed closely while receiving CyA at full dose. In principle, cyclosporine should be given IV or orally in full dose from Day –1 until day 60, then be tapered, in the absence of GvHD, and stopped at day +120. However, if Graft versus host Disease (GvHD) occurs, or if justified by chimerism data, CyA dose and duration should be individualized CyA and short course methotrexate. This immunosuppression combination includes full dose CyA and methotrexate. The dose of methotrexate is 15 mg/sqm IV day 1, 10 mg/sqm day 3 and day 6. The use of folinic acid rescue on days 4 and days 7 –10 is optional. A fourth dose (10 mg/sqm) of methotrexate Day +11 with optional use of folinic acid rescue on day +12, should be added after MUD-RICT, or otherwise if the risk of GvHD is considered high. The immunosuppression combination of CyA and MMF includes full dose CyA and MMF. The CyA dosage schedule is described above. The MMF dose, either orally or IV, is 15 mg/kg twice daily. Doses will be rounded to the nearest 250 mg (capsules are 250 mg). Most patients will receive 1000 mg twice daily. After MSD-RICT, and in the absence of GvHD, MMF will be given until day +50 post-treatment and then stopped without tapering. After MUD-RICT, MMF will be given 15mg/kg every 8 hrs to day +40, then tapered to day +96. If there is nausea and vomiting, preventing oral administration, MMF dose should be reduced accordingly, or administered intravenously. GvHD should be treated as per local routines with prednisone/prednisolone. In case of steroid-refractory GvHD, defined as progression after three days or no improvement after 7 days or incomplete response after 14 days of corticosteroid treatment, patients will be managed according to local practice or ongoing studies. Chronic GvHD will be treated according to local practice. Most centers have developed routines for chimerism assessment and immunological intervention. Therefore, only some principles are stated and centers are free to use their own routines as to the rest. For the purpose of this trial, chimerism analysis should be performed at least in PB at +1 month, at D +100 and at 1 year in PB or BM. Extra assessments may be needed in case of remaining MRD or administration of DLI. It is recommended to assess chimerism in T-cells and myeloid cells separately. Remaining or reappearing of host myeloid cells may be used as surrogate marker for MRD. Immunological intervention such as CyA taper or DLI may be considered. SURVEILLANCE AND INTERVENTION: Local or national routines for surveillance and intervention will be applied. Participants in the second study group will not undergo RICT as a suitable bone marrow donor was not available. Instead, they will receive conventional consolidation therapy according to institutional practice or within studies of post consolidation therapy. It is presumed that the participants in this group will receive a total of 3-4 chemotherapy courses. Participants in this group who relapse will be treated at the discretion of the clinician. Relapsed patients may receive any salvage treatment.

The study will assess the feasibility of a specified exercise program in patients with advanced breast cancer and its impact on improving fatigue. Who is it for? You may be eligible to join this study if you are a female with metastatic breast cancer aged between 18-80 years, and are being managed at Breast Cancer Research Centre- WA. Eligible women will also have experienced subjective fatigue in the past several weeks as a persistent symptom. Study details This study will be conducted in two parts. In Part 1, eligible patients will be offered a 6 week exercise program, where the primary endpoint will be to assess feasibility and overall safety. If the program is deemed as being feasible and safe, Part 2 of the study will commence. In Part 2, participants will be randomly (by chance) allocated to one of two groups. Participants in one group will be offered the 6 week exercise program, whilst participants in the other group will not participate in the exercise program. On completion of the program, participants will be asked to complete some questionnaires to assess their levels of fatigue, depression and pain. They will also be asked to conduct a brief walking test to assess any changes in aerobic fitness.

This trial is aimed at determining if Glyceryl Trinitrate given by the surgeon prior to haemorrhoid banding during colonoscopy reduces peri-operative pain and need for analgesia when compared against placebo.

Each year, about 2 in 3 adults living in aged care centres falls at least once. These falls can have serious consequences such as injuries and mobility limitations or fear to fall again. Churches of Christ Queensland have designed an exercise program to prevent falls and improve balance among residents of aged care centres. This study aims to evaluate the feasibility and efficacy of this exercise program. The outcome of this study will help inform and facilitate ongoing improvements in falls prevention and management.