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Pelvic organ prolapse (POP) is a common gynaecological condition which has been observed in up to 50% of women above 50 and has an associated 20% risk of surgery during a woman’s lifetime. Despite impacting the lives of millions of women in our society, there are few options available for preventing or addressing this condition. Defined as the downward displacement of one or more pelvic organs into the vagina, POP can significantly impact the quality-of-life of women with the condition. It has a number of causes including injury from vaginal birth/pregnancy, and is exacerbated by ageing, obesity, genetics, constipation, chronic coughing, heavy lifting, and smoking. Severity is graded using the Pelvic Organ Prolapse Quantification (POP-Q) tool which classifies the degree of descent using the hymen as a reference point. Stages of descent vary from minor descent (Stage 1) to the complete external presentation of the organ (uterus, bladder, bowel) through the vagina (Stage 4). Symptoms include a heavy sensation or dragging feeling in the vagina, a lump in the vagina, a lump which bulges out and can be felt or seen when standing, painful intercourse or loss of sensation, difficulty emptying the bowel or bladder, recurring urinary tract infections, and faecal or urinary incontinence (UI). According to a report by the Australian Institute of Health and Welfare, UI alone accounts for >$200 million each year in healthcare expenditure in Australia, with drastically more women being affected than men for this condition. Current clinical protocols primarily have a passive management focus, which includes lifestyle changes or simple intravaginal pessaries, both of which require long-term (often until surgery or end-of-life) investment and adherence by patients; or a rehabilitation focus where pelvic floor muscle training attempts to strengthen the pelvic floor muscles. On the spectrum of invasive practices, 10-20% of women will undergo surgical intervention. However, surgery carries a number of risks, contraindications, and has the disadvantage that up to a third of women may have a recurrence. Additionally, vaginal mesh procedures introduced to reduce the risk of recurrence caused unacceptable adverse events and are no longer approved. Due to these limitations with current management protocols, there is a demand for novel non-surgical treatments which can improve or cure the condition. IVES could play a role in rehabilitating the pelvic floor muscles of women with POP. It does this by triggering neuromuscular contractions in the pelvic floor which may either increase muscle bulk or tone muscles to improve their ability to support the organs. With research suggesting that IVES may be effective at treating UI and at increasing pelvic floor muscle strength, it is possible that IVES may be an effective treatment for mild-to-moderate POP. This study aims to develop a heat map of the optimal intravaginal regions to target with IVES to improve efficacy of IVES.

Inflammatory Bowel Disease (IBD) is a chronic gastrointestinal disease, affecting approximately 1 in 250 Australians. Ulcerative colitis is a sub-type of IBD. Scientific research exploring the effectiveness of nutritional therapies in adults with Ulcerative Colitis has not yet found many definitive conclusion, therefore more research is needed. In addition, research testing how these nutritional therapies change the gut microbiota may be beneficial at developing anti-inflammatory nutritional therapies that help to manage this burdensome disease. There is a lack of clinical trials that have tested both changes to inflammatory markers and the gut microbiota in adults with inflammatory bowel disease, after taking a microbiota-modulating therapy. Plant athocyanins and probiotics have both been shown to reduce inflammation, however not enough to be effective in adults with IBD. In this study, we plan to test for the first time whether combining both an anthocyanin and a probiotic will result in more effective reductions in inflammation and therefore beneficial disease control. This study aims to evaluate the effectiveness of a multi-strain probiotic intervention provided together with dietary anthocyanins extracted from the New Zealand Blackcurrants on the gut microbiota profile and inflammatory biomarkers in adults with mild-moderate Ulcerative Colitis. We hypothesise that the combination of anthocyanins and probiotics will lead to reduction in gut inflammation in participants (measured through faecal calprotectin), and will alter the gut microbiota. We hypothesise that these improvements will be more significant in participants who take the combined intervention (anthocyanin + probiotic) rather than participants who take the anthocyanin alone or probiotic alone.

SUMMARY Study title: Ex-vivo confocal microscopy: diagnostic accuracy, acceptability & feasibility This study is investigating the accuracy of a new method of analysing skin biopsies using a high-powered microscope to determine the diagnosis (for example, skin cancer, inflammatory skin condition) and whether the lesion is clear of the surgical margins or not. Who is it for? You may be eligible for this study if you are an adult aged 18 years or older, you have one or more skin lesions that need to be investigated and you are willing to have a biopsy (tissue sample) taken, when a biopsy is recommended for you as standard care by your treating doctor.. Study details All participants who choose to enrol in this study will not be asked to provide any extra skin samples that they would not already be providing as part of their standard clinical care. Participants who choose to enrol in this study would give permission for up to three of their skin biopsies to be examined with the new microscope. The skin biopsies will then undergo further preparation for scanning with the new fusion ex-vivo confocal microscope (fevCM) system and will also be assessed by the standard histology (staining of the tissue) analysis method. It is not anticipated that participation in this study will require additional time or travel commitments from patients. It is hoped this research will determine whether the new microscope method of assessing skin tissue is comparable to the standard assessment methods in terms of accuracy and time needed to prepare and analyse tissue samples. If the new microscope system is found to be accurate and quicker than the current assessment methods, use of this technology may be expanded to a greater number of patients.

This study is a mixed-methods study, combining an open-label pragmatic parallel group randomised controlled trial (RCT) with qualitative methodology investigating the effect of different milk proteins on brain, immunity, gut and skin health outcomes. There is evidence that different forms of beta-casein proteins, found naturally in milk, have different effects on health. There is also some evidence of an interconnection between the brain, immune, and skin systems linked by the gut microbiome. This study aims to determine the effect of milk containing only a2 beta-casein protein on brain health, immunity and inflammatory markers, gastrointestinal function, and skin health as compared to conventional milk which contains A2 and A1 beta-casein, in healthy older adolescents and adults (16-65 years) in a real world setting. Participants (n=1000) will be randomised to each study arm. The study period goes for 30 days including a 2 day run-in and 28-day intervention. Outcomes will be measured at the start, middle and end of the intervention period. The first 260 participants will be required to have a saliva sample and faecal sample collected pre and post intervention and complete questionnaires at each time point. The remaining 740 participants will complete questionnaires at each time point only. There will additionally be a short (1 min) survey sent twice a week to monitor for adverse events. Participants from the intervention group will be randomly selected and invited to participate in the nested qualitative study (n=30). The study has been planned in accordance with the Declaration of Helsinki, National Health and Medical Research Council National Statement on Ethical Conduct in Human Research. All staff with direct participant contact have completed Good Clinical Practice Guideline training and certification.

Primary aim: To examine the efficacy of heel lifts versus sham on pain intensity among individuals with mid-portion Achilles tendinopathy at 3 months. Secondary aim: to investigate the acute biomechanical effects of heel lifts among individuals with mid-portion Achilles tendinopathy. The primary outcome measure will be pain intensity (at its worst) at 12 weeks. Study hypothesis: Heel lifts will lead to a superior outcome in the pain intensity measure compared to sham at 12 weeks.

The Daughters and Dads Active and Empowered Program is an intervention which engages fathers in positive lifestyle role modelling and effective parenting strategies to improve the physical activity behaviours, physical confidence, sport skills and social-emotional wellbeing of their daughters. Importantly, the program also targets girls to improve their fitness and physical activity levels, and parenting skills of their fathers. This mixed-methods, observational study is a follow-up of participants from previously registered studies, including: ACTRN12615000022561 (2015), ACTRN12616001270404 (2016), ACTRN12617001450303 (2017-2019) and ACTRN12621000264886 (2020). The purpose is to evaluate the impact of the Daughters and Dads community-based program beyond the initial effects, on longer-term, real-world impacts upon the outcomes mentioned above. Establishing the long-term effectiveness of the program: • would be an important and novel contribution to the literature. • may inform future iterations of the programs. • will help provide evidence as to whether additional scale-up of the program is worthwhile with current and future agencies who may wish to fund the scale-up of this evidence-based program, thus providing greater reach to families across the state, nationally and internationally.

INFORM-AF II is a pilot prospective, randomised, open-label, blinded endpoint (PROBE), multicentre trial of a digital atrial fibrillation (AF) education program delivered via QStream™ versus the Stroke Foundation ‘Living with AF’ booklet. The aim of the study is to evaluate the effectiveness of the digital AF education program delivered via QStream™ on re-hospitalisation rates within 12-months of the primary indexed AF diagnosis, all-cause mortality, cardiovascular-related hospitalisation, medication adherence, AF-related knowledge, and quality of life as well determine the cost-effectiveness of the intervention. The mHealth application is a smartphone-based spaced learning intervention and consists of six case scenario-based AF questions, based on a spaced timing algorithm, delivered over a 6-week period. The mHealth-based intervention is delivered by the QStream digital platform and was co-designed in consultation with stakeholders including patients living with AF, healthcare providers of AF patients and key opinion leaders from the Stroke Foundation, Heart Foundation, non-government organisations and cardiovascular peak bodies. This trial is informed by our foundational qualitative research which explored the educational and self-management needs of adults living with AF and a recently completed single group feasibility and acceptability study (INFORM-AF) which demonstrated significant improvements in AF knowledge and quality of life at 12 months (yet to be published). Data collection will be completed through an electronic survey delivered by the study nurse over the phone at 6 weeks, 3 months, 6 months, and 12 months post intervention.

Diuretics are commonly used in the intensive care unit with the aim of achieving a negative fluid balance; yet remarkably little is known about their pharmacodynamic properties in critically ill patients. The most frequently used class of diuretic drugs are the loop diuretics, and furosemide is the most commonly used loop diuretic. However, loop diuretics may have a number of undesirable side effects, including electrolyte derangements and metabolic alkalosis. This pilot trial will randomly allocate 40 patients (20 in each arm) to receive Furosemide only or Furosemide and Acetazolamide. The primary outcome is urinary output occurring in the 6 hours after diuretic administration while in the intensive care unit. Results will inform future clinical trials and the outcomes that will be selected for these future trials.

This is a pilot study which aims to assess the response to the use of prednisolone in people with artificial stone associated silicosis. The pilot study will assess safety, feasibility, and explore the effect of prednisolone on clinical outcomes (markers of disease activity) before and after treatment. Participants will include people with artificial stone-associated silicosis who have elevated indicator(s) of inflammation despite cessation of exposure to silica dust. Participants will be treated with 25mg prednisolone daily for three months.

The purpose of this study is to evaluate clinical efficacy of incorporating Epcoritamab into the salvage regimen for relapsed-refractory aggressive B-cell lymphoma, followed by autologous stem-cell transplantation (ASCT) and consolidation Epcoritamab. Who is it for? You may be eligible for this study if you are aged 18 and above and are transplant-eligible with diffuse large B cell lymphoma that has relapsed or progressed after at least one line of immunochemotherapy. Study details This study design involves phases for Epcoritamab-Salvage treatment, ASCT and Consolidation treatment. 1. Epcoritamab-Salvage treatment: Salvage treatment consists of 3 cycles of R-DHAOx (rituximab, dexamethasone, cytarabine, oxaliplatin) plus Epcoritamab, given in 21 day cycles. Epcoritamab is commenced in cycle 1, consisting of weekly dosing on days 1, 8 and 15, three doses per cycle. Priming (0.16mg) on C1D1 and intermediate (0.8mg) C1D8 dosing will be administered prior to full dose (48mg) on C1D15 and ongoing. Response assessment will be performed after 2 cycles of Epcoritamab-salvage according to Lugano Criteria 2014. • Patients who achieve complete remission (CR) may proceed directly to ASCT or may receive 1 further cycle of combination Epco-R-DHAOx and then proceed to ASCT. • Patients who achieve partial response (PR) will receive 1 further cycle of combination Epco-R-DHAOx and proceed to ASCT or may cease protocolised therapy based on physician choice and enter the Post Treatment follow up phase. • Patients achieving less than PR will not receive further protocol therapy and will enter overall survival (OS) follow up. 2. Autologous stem cell transplant: Stem cell collection will occur following either the second or third cycle of salvage Epcoritamab as per institutional policies. Stem cell recollection is allowed in the event of unsuccessful first collection. Pre-autograft eligibility assessment for ASCT will be performed according to local practice. ASCT may be administered at local referring centre and will follow local standard operative procedures. • Note: Patients who respond to salvage-Epcoritamab treatment but are not considered eligible for the transplant procedure for reasons other than insufficient response (e.g. due to toxicity or failed stem cell mobilisation) may proceed directly to the Consolidation Phase instead of proceeding to ASCT BEAM chemotherapy will be used for conditioning as per institutional guidelines. 3. Consolidation treatment: Consolidation treatment consists of six 28-day cycles of subcutaneous Epcoritamab, commencing between 6 and 12 weeks post ASCT. Other testing that will be performed includes physical examination, neurological examination, ECOG performance, ECG, haematology, biochemistry and monitoring of adverse events. It is hoped this research will prove the safety of Epcoritamab in this “sandwich” design with ASCT in relapsed-refractory aggressive B-cell lymphoma