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Influenza infection is a frequent and important problem in chronic obstructive pulmonary disease (COPD). Influenza can have severe consequences in these patients, leading to acute exacerbations of COPD, pneumonia and respiratory failure. COPD patients are thus recognised as a group at particular risk of influenza, and current guidelines recommend yearly influenza vaccination. These recommendations are largely based on expert opinion and observational studies, with very few randomised controlled trials having been conducted in COPD. It has been suggested that people with COPD may have an aberrant immune response to influenza viruses, and as such, they may be less able to effectively mount an immune response to influenza vaccination. This study will examine influenza vaccination in people with COPD, and healthy age-matched controls, focussing on the factors that predict an effective antibody response to the vaccine (seroprotection), especially aspects of dendritic cell and T-cell function. We will conduct an open-label observational study of seasonal influenza vaccine in 108 COPD patients and 108 healthy, age-matched control subjects. Subjects will receive a single dose of inactivated and purified split influenza vaccine in the autumn of 2015, 2016 and 2017. Primary outcomes of this study will be the proportion of vaccine recipients who achieve seroprotection or seroconversion.

Paradigm Biopharmaceuticals Ltd (Paradigm) is focusing on Pentosan Polysulfate Sodium (PPS) for the treatment of conditions that are associated with inflammation and progress chronically with tissue degeneration, including the treatment of Osteoarthritis Knee pain. Previous studies demonstrate that PPS is tolerated at the proposed dose (2 mg/kg) and duration (once or twice weekly for 6 weeks). While most of the clinical data obtained were acquired using a twice weekly regimen, a once weekly SC injection program, if effective and safe, would be ideal for feasibility. This study is will assess safety, tolerability, and pharmacokinetic responses of multiple sub-cutaneous doses of PPS in a healthy western population to support the development program. The clinical and nonclinical evidence demonstrate that PPS is tolerated at the proposed dose (2 mg/kg) and duration (once or twice weekly for 6 weeks). In two studies evaluating dose limiting toxicity, maximum tolerated doses were determined to be 3 mg/kg/day continuous infusion (Pluda et al., 1993) and 22.5 mg/m2 SC injection every 6 hours (Swain et al., 1995). Assuming an average male of 60 kg and 1.9 m, these doses are roughly equivalent to 180 mg/day and 171 mg/day, respectively. These levels are greater than the Sponsor’s current proposed dosing regimen of 2 mg/kg (approximately 120 mg) SC once or twice per week. The PK sampling design in this study will allow comparison with an earlier PK study which evaluated 50 mg to 300 mg PPS administered by SC injection once weekly for 4 weeks. While most of the clinical data obtained were acquired using a twice weekly regimen, a once weekly SC injection program, if effective and safe, would be ideal for feasibility. Therefore, PK data obtained from once and twice weekly dosing regimens will support the development program.

The T-POT study will assess a brain pulse oximeter designed to non-invasively monitor brain oxygen and brain blood flow in patients requiring acute neurological monitoring in the hospital or intensive care unit (ICU) with acute brain injury or at high risk of acute neurological deterioration. It is known that patients with an acute brain injury are at risk of neurological deterioration, typically as a result of low blood flow in the minutes, hours or days after the initial injury. Available brain monitoring is highly invasive and therefore only used in the most severe cases. An accurate non-invasive method to monitor brain oxygen levels and brain blood flow would facilitate monitoring in more patients and earlier detection and treatment of acute neurological deterioration. This could improve healthcare outcomes, reducing both long-term disability and death. The T-POT pulse oximetry technology can monitor oxygen levels and blood volume changes in organs of the body, including the brain. The sensor and algorithms of the Brain Pulse Oximeter were developed to overcome limitations of conventional pulse oximeters that only provide oxygen and a photoplethysmogram (PPG) signal from blood flow in the skin. The PPG detects blood volume changes in the microvascular bed of a tissue. The major aim of the study is to assess the correlation of the brain pulse oximeter oxygen levels with invasively measured cerebral perfusion pressure (CPP).

This study is designed to assess the rate of response to treatment (subcutaneous golimumab 50mg given four weekly) on MRI and other clinical RA measures in 12 participants diagnosed with active rheumatoid arthritis with inadequate response to Methotrexate. Study duration is 12 weeks. The aim is to assess at what timepoints specific MRI changes are seen with golimumab use; which aspects of rheumatoid involvement respond earliest; and if this precedes the timepoints when other clinical RA outcome measures change. Clinical response to treatment will involve assessing response to treatment on MRI of the participant’s most affected hand/wrist (as determined by Investigator assessment by examination at screening), as well as clinical outcome measures such as CRP, ESR and joint count assessments. In addition, participant reported outcomes (PROs) will be completed to assess the overall disease activity levels as reported by the participant. The PROs chosen include the conventional PROs EQ-5D, SF-36, FACIT-F and PtGA as these are well-established PROs that have demonstrated validity and reliability in assessing disease state, as well as a specific upper limb function PRO, the DASH. Visit timepoints are baseline, week 2, week 6 and week 12. At the end of the study, the participant will return to their normal treating rheumatologist for ongoing care.

This case-control study aims to identify whether correcting serum parathyroid hormone (PTH) after parathyroidectomy would have an effect on the clinical criteria for frailty, which are highly prevalent in older persons suffering from primary hyperparathyroidism (pPTH). Women (60 and older) undergoing neck exploration for pHPT will be assessed for general functional parameters (gait, balance, and muscle power and strength) and clinical criteria for frailty (Fried’s criteria) before and after (3 months) surgery. Women of the same age undergoing neck exploration for benign nontoxic goiter will serve as controls. This study will provide a new understanding of the role of PTH in the pathophysiology of frailty. We will also identify novel potential interventions to prevent frailty, falls and fractures in high-risk older persons with alterations in their calciotropic hormones.

This study will look at a patient-specific, remotely monitored, dose measured cycling exercise program following knee surgery. This new method uses a remotely-monitored bicycle power meter in order to prescribe and modify an exercise regimen. We hypothesize that patients who complete a patient-specific cycling exercise program following this surgery will have better short- and long-term outcomes than those who complete a non-cycling post-operative program.

Complications of MPS I include pain and functional symptoms. The aim of the study is to assess the safety of the investigational product pentosan polysulfate (PPS) in patients with MPSI, and to determine if PPS can successfully alleviate pain and functional symptoms in MPS I patients who have received ERT and/or haemopoietic stem cell transplantation (HSCT). Up to 10 participants (males and females aged 5 years or greater who meet the inclusion criteria) are expected to be enrolled. This is an open label study, in which participants will be sequentially assigned to receive either 0.75 mg/kg or 1.5 mg/kg of PPS via subcutaneous injection. PPS will be administered weekly for the first 12 weeks and then every second week until the end of the study. The study will run for 73 weeks from baseline. Following the screening visit, the participants will be required to attend the hospital for assessments out to week 73. Many of the scheduled visits may occur at the patient’s home by a member of the study team. There will be a final study visit involving assessments 5-7 days after the last PPS administration. There will be a final study visit involving assessments 5-7 days after the last PPS administration.

Posttraumatic stress disorder (PTSD) is the most common psychiatric disorder that develops following exposure to a traumatic event, such as interpersonal violence, combat, life-threatening accidents, or natural disasters. It is characterised by severe and persistent stress reactions including: intrusive memories and nightmares of the trauma, hypervigilance, difficulty sleeping, emotional withdrawal, pervasive negative emotions, and avoidance of places, activities, and situations that are reminiscent of their trauma. The treatment of choice for posttraumatic stress disorder (PTSD) is trauma-focused psychotherapy. Trauma-focused psychotherapy typically commences with psychoeducation about the trauma responses, and then focuses on three major strategies: anxiety management, exposure, and cognitive restructuring. Despite support for this therapeutic approach, meta-analyses indicate that at least one-third of patients do not respond to this treatment. Whilst extant treatments have shown success in reducing negative affect, they have had limited effect on increasing positive affect.This may be because extant treatments have focused solely on addressing symptoms reinforced by the withdrawal/defensive system and ignored the need to increase approach/appetitive responding, that results in increased positive affect. Modifying TF-CBT to include strategies that specifically target the approach/appetitive system may address a gap in available treatments that fail to address symptoms of dysphoria and anhedonia. Positive Affect Training aims to restore positive moods in participants alongside traditional extinction learning which reduces over-activation of the withdrawal/defensive motivation system associated with negative affect. To address the gap in augmenting the benefits of TF-CBT, this trial aims to test whether modifying TF-CBT to augment it with strategies to address anhedonia via Positive Affect Training will result in greater treatment gains relative to TF-CBT.

This study aims to determine the possibility and to examine if a short- term pelvic floor rehabilitation program can improve bowel issues after bowel cancer surgery with or without radiochemotherapy. Who is it for? You may be eligible for this study if you are an adult experiencing bowel issues after surgery for colorectal cancer. Study details Participants in this study will receive: 1. Education on normal bowel function and the bowel issues associated with colorectal cancer surgery. They will also receive information on good bladder and bowel habits, dietary advice, and pelvic floor exercises. 2. A 10 week face to face program of weekly attendance to the outpatient clinic for 1 hour under supervision (ie 1 hour session, once per week for 10 weeks in an outpatient clinic). The program includes: pelvic floor muscle strength training with use of an non- invasive technique called transperineal ultrasound for visual biofeedback, and anorectal sensory and coordination retraining using an minimally invasive technique called rectal balloon catheter biofeedback. Participants will also be instructed to practise home exercises and to complete a daily pelvic floor exercise diary. It is hoped that this research will determine the possibility of a short-term pelvic floor rehabilitation program for patients with bowel dysfunction after colorectal cancer surgery and treatment in an outpatient setting as well as identify the signals of benefit of pelvic floor rehabilitation for the improvement of bowel function and quality of life.

Exercise intolerance is a major cause of morbidity and a predictor of mortality in patients with heart failure (HF). Although many patients with HF have a dilated left ventricle and reduced ejection fraction, approximately 50% of patients have clinical manifestations of HF with a normal sized heart and normal systolic function. As such, HF is now categorised as reduced (HFrEF) vs preserved (HFpEF) ejection fraction. An important distinction of HFpEF patients is that traditional pharmacological therapies used to treat HFrEF have not improved quality of life or survival. There is currently limited understanding of HFpEF pathophysiology, thus there is a need for investigations that will lead to novel therapeutic approaches in the treatment of this condition. It is now appreciated that leg muscles become dysfunctional in HF, and generate an abnormal neural signal (a 'metaboreflex') that disrupts cardiovascular and respiratory control, enhancing ventilation and breathlessness, causing exercise intolerance (EI). A similar metaboreflex occurs within respiratory muscles, which reduces blood flow to the active limbs in these patients, exacerbating the metaboreflex arising from the legs in a detrimental positive-feedback manner, hastening the onset of breathlessness and EI. However, no studies have directly compared this reflex physiology in HFrEF and HFpEF. This proposal aims to identify metaboreflex contribution to EI by determining if the leg and respiratory muscle metaboreflexes contribute equally to EI in both HFrEF and HFpEF, their influence on cardiac function, and if exercise training attenuates metaboreflex signalling. The outcomes of this proposal will have clinical relevance and lead to the development of novel therapeutic interventions, through a combination of exercise prescription and pharmacological targeting of the metaboreflex in the early stages of HF and may lead to an elusive therapy that will improve quality of life and survival in patients with HFpEF.