ANZCTR search results

This project aims to identify the prevalence of POTS in patients who attend the emergency department with symptoms consistent with this condition, using a novel diagnostic pathway. A validated patient reported survey will be used to predict the likelihood of POTS in patients whose symptoms are consistent with POTS based on their hospital presentation. Participants who progress to the next stage of the study will complete objective autonomic testing to quantify the presence of POTS. As there is limited prevalence data on POTS available, and given that testing for POTS in a general symptomatic population has not been tested before, we have elected not to hypothesize a prevalence in this population.

Existing treatments for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are inadequate and ME/CFS therapy represents an unmet need of healthcare. Our aim is to assess the efficacy of trimetazidine, a metabolic agent, in treating ME/CFS in a double-blind, randomised, placebo-controlled clinical trial. Mitochondrial dysfunction has long been associated with inflammation and oxidative stress of ME/CFS and may be the potential final common pathway in the pathophysiology of ME/CFS. Trimetazidine increases metabolic efficiency in the mitochondria by promoting glucose oxidation rather than fatty acid oxidation (i.e. increased energy generation) and has anti-inflammatory and antioxidant properties. Importantly, in preclinical rodent studies confirmed trimetazidine increases mitochondrial function in the brain and facilitates longer swimming in the forced swim test without causing hyperactivity in the large open field. Trimetazidine was also identified using an atheoretical drug screening approach that showed trimetazidine to redress mitochondrial dysfunction. The therapeutic potential of trimetazidine is clear, Trimetazidine is highly accessible, affordable, and has regulatory approval to treat angina in Asia and Europe, making it particularly suitable to repurpose for ME/CFS.

This is a study to determine if the FUNCAP 27 can be used as an instantaneous measure of perceived functional capacity in those with ME/CFS and Long Covid when at baseline and in a state of PEM(Post Exertional Malaise). We are doing this to establish a measure that can detect short term fluctuations in health that will be used in later interventional clinical trials. We aim to recruit 1000 participants for 2 questionnaires and 1 enrolment survey taking 6-20 minutes at enrolment (including reading the consent forms), 15-35 minutes when well and 10 -20 minutes in PEM. The questionnaire can be completed with the aid of a carer and paused for completion at a later time.

The prevalence of chronic fatigue is high in Australia. There is a need for better understanding of underlying disease patho-physiology and reliable assessments of treatment effectiveness. This intervention study aims to assess the treatment effect of Electromagnetic Frequency (EMF) therapy for patients with chronic fatigue using the viral reactivation test, a combination of the cytology-based Circulating Rare Cell (CRC) blood test, and viral marker testing for dormant viruses such as Epstein Barr Virus (EBV), Cyto-megalo-virus (CMV), or Herpes Simplex Virus (HSV). Who is it for? You may be eligible for this study, if you have chronic fatigue. Study details Patients will undergo an intial EMF session of 60-90 min to assess treatment effectiveness of the chosen patient-specific frequency program. Effectiveness will be assessed by blood tests measuring the number of viral reactivated Circulating Rare Cells (CRC) before and 1 day after treatment. If successful, the patient will discuss with their health practitioner a 12 week treatment plan, which may involved twice weekly EMF sessions for 12 weeks. A follow-up CTC test at 3 and 6 months is scheduled to assess treatment effectiveness in the context of long-term clinical outcome. It is hoped, that this study will provide insight into the effectiveness of EMF therapy for viral reactivated chronic fatigue, with the aim to reduce viral reactivation and improve symptoms and quality of life.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is a debilitating illness affecting up to 24 million people worldwide but concerningly there is no known mechanism for ME/CFS and no objective test for diagnosis. A series of our neuroimaging findings in ME/CFS, including functional MRI (fMRI) signal characteristics and structural changes in brain regions particularly sensitive to hypoxia, has informed the hypothesis that abnormal neurovascular coupling (NVC) may be the neurobiological origin of ME/CFS. NVC is a critical process for normal brain function, in which glutamate from an active neuron stimulates Ca2+ influx in adjacent neurons and astrocytes. In turn, increased Ca2+ concentrations in both astrocytes and neurons trigger the synthesis of vascular dilator factors to increase local blood flow assuring activated neurons are supplied with their energy needs. This study will investigate NVC using multimodal MRIs: 1) hemodynamic response function (HRF) that represents regional brain blood flow changes in response to neural activities and will be modelled from a cognitive task fMRI; 2) respiration response function (RRF) that represents autoregulation of regional blood flow due to carbon dioxide and will be modelled from breath holding fMRI; 3) neural activity associated glutamate changes that will be modelled from a cognitive task functional magnetic resonance spectroscopy. We also aim to develop a neuromarker for ME/CFS diagnosis by integrating the multimodal MRIs with a deep machine learning framework. This cross-sectional study will recruit 288 participants (91 ME/CFS, 61 individuals with chronic fatigue, 91 healthy controls with sedentary lifestyles, 45 fibromyalgia). The ME/CFS will be diagnosed by an agreed diagnosis made by two clinicians using the Canadian Consensus Criteria. Symptoms, vital signs, and activity measures will be collected alongside multimodal MRI. The HRF, RRF, and glutamate changes will be compared among four groups using one-way analysis of covariance (ANCOVA). Equivalent non-parametric methods will be used for measures that do not exhibit a normal distribution. The activity measure, body mass index, age, depression, and anxiety will be included as covariates for all statistical analyses with the false discovery rate used to correct for multiple comparisons. The data will be randomly divided into a training (N = 188) and a validation (N = 100) group. Each MRI measure will be entered as input for a least absolute shrinkage and selection operator - regularized principal components regression to generate a brain pattern of distributed clusters that predict disease severity. The identified brain pattern will be integrated using multimodal deep Boltzmann machines as a neuromarker for predicting ME/CFS fatigue conditions. The receiver operating characteristic curve of the identified neuromarker will be determined using data from the validation group.

Chronic physical illness (e.g. diabetes, epilepsy, asthma, autoimmune disease) affects 10-20% of Australian youth and can involve frequent pain, intensive treatment, and major limitations in daily activities. This can have serious impacts on well-being and mental health. In order to address this, we need engaging and accessible interventions to improve well-being and mental health among young people with chronic conditions. We aim to find out whether online self-compassion training improves mental health and well-being in adolescents and young adults with chronic illness. Self-compassion involves treating yourself with the same kindness and understanding as you would a good friend. In self-compassion training, people learn to skills to be kinder to themselves and soothe themselves when they are distressed. This helps them to recover from difficult experiences more quickly. Online programs may be preferable for people with a chronic illness as they are accessible and flexible. We have developed a four-week online program to help people learn self-compassion skills. A We will trial the program with young people (16-25 years) with chronic conditions. We will test whether people doing the program have significant improvements in psychological distress and well-being, compared to people on a waitlist. We will also explore whether any improvements in these outcomes are driven by increases in self-compassion or emotion regulation skills.

Debilitating fatigue; unrefreshing sleep and poor daytime functioning are core features of many neuropsychiatric conditions including chronic fatigue syndrome (CFS) and major depression. Understanding of the aetiologies of these conditions is still incomplete and symptom management strategies have only limited efficacy. Accumulating evidence suggests that abnormalities in the function of the autonomic nervous system play a role in the sleep disturbance and chronic fatigue in these conditions. In particular, autonomic activity is characterized by neural hyper-vigilance and a marked loss of parasympathetic, vagus nerve activity that persist even during sleep. Measures of beat-to-beat heart rate variability (HRV) provide well-established, reliable indices of autonomic functioning, which consistently correlate with the severity and outcome of a spectrum of fatiguing disorders, including autoimmune and cardiovascular disease, chronic pain, depression, and CFS . For example, low HRV was repeatedly found to be a strong correlate of unrefreshing sleep, daytime fatigue and cognitive impairment in CFS. Mindfulness-based stress reduction and relaxation methods are increasingly utilised with the aim to restore autonomic balance. It is believed that the beneficial effects of these approaches are mediated via their impact on neural circuits involved in self-regulation, and on key stress-response pathways. However, individuals can have very different responses to different relaxations methods; and recent analyses revealed that some patients do not respond optimally to some. The main of the current study is to conduct a randomized control trial (RCT) to determine the efficacy and specific benefits of a 4 week personalised relaxation intervention, pre-tested to optimise the individuals' own HRV. Subjective health outcomes and parasympathetic autonomic activity (indexed by HRV) in patients with CFS and depression will be compared to a ‘monitoring only’ control condition. We anticipate that daily practice of a personalised relaxation method before sleep will be substantively more effective in improving sleep quality, daytime fatigue and functioning in both patient groups compared to treatment as usual with symptom monitoring. We further anticipate that restoration of HRV will contribute to positive health outcomes. The findings from this research will facilitate a better understanding of the pathophysiological mechanisms operating in chronic fatigue conditions.

The survival of an organism in the face of internal and external events requires a measured and appropriate stress response. It has been hypothesised that an abnormal stress response is linked to the likelihood of the development and severity of critical illness and multi-organ failure. The stress response is coordinated by the primitive brain structures of the diencephalon and brainstem in response to somatosensory inputs and comprises a broad range of neuro-hormonal and immune effects. We hypothesise that the use of sedating medications confuses the normal generation of a stress response. If this is confirmed, this may be a fundamental underlying cause for the abnormal haemodynamics, metabolic disturbances and organ dysfunction observed in critical illness. The large multi-centre randomised-controlled SPICE-III study offers the opportunity to study two similar groups of patients who may have differing levels of physiological stress as a result of an Early Goal-Directed Sedation (EGDS) strategy as compared to standard care. We aim to conduct a substudy to determine whether a strategy of EGDS and the resultant reduced sedation level results in a differing physiological stress response in critically unwell patients as measured by a panel of blood-borne markers. We hypothesise that the application of an early goal directed sedation protocol and the resultant reduced sedation level in the first 5 days of critical illness will result in a differing pattern of stress as measured by metabolic, sympathetic, hormonal and inflammatory responses. All-SPICE will be a prospective parallel-group multi-centre observational sub-study of the the SPICE-III study. The SPICE-III study is a prospective, un-blinded, randomised controlled trial of Early Goal-Directed Sedation compared with Standard care. The SPICE-III study will recruit patients who are intubated and ventilated in a participating ICU, are expected to remain intubated the day after enrolment and need immediate and ongoing sedation. Due to the immediate need to choose a sedative regimen for ongoing patient safety and comfort, it is proposed that study enrolment will occur using deferred consent. A total of 100 patients from approximately 4 ICUs will be enrolled in All-SPICE. Immediately following randomisation on day 1, patients will have blood samples taken, which will be repeated on days 2, 4 and 6. These samples will be assessed for various blood-borne markers which are considered to be potentially affected by the coordination of the stress response.

A post-exertional exacerbation of fatigue and other symptoms is a characteristic feature of chronic fatigue syndrome (CFS) following a relatively small amount of physical or cognitive activity. Although it is well established that graded exercise therapy (GET) is beneficial for the management of CFS, this intervention, which uses cautious, symptom-limited increases in gentle aerobic exercise, has only modest effectiveness. The key limiting factor is the delayed exacerbation of symptoms that follows exercise. This post-exertional exacerbation has been well characterized in exercise challenge studies. Modafinil, a psycho-stimulant drug, has been licensed in Australia and internationally and used clinically for some time. Additionally, it has demonstrated some benefit in reducing fatigue in multiple sclerosis, and daytime sleepiness in Parkinson’s disease. In healthy subjects, the effect of a single dose of modafinil on exercise time has been examined and showed a prolonged time to exhaustion of 22% for high intensity exercise (Jacobs and Bell, 2004). Interestingly, the rate of perceived exertion (RPE) reported by participants was statistically significantly lower in the modafinil exercise trial compared to the placebo exercise trial. Since the symptom of fatigue is the limiting factor in the progression of GET, it is appealing to test the possibility that modafinil may attenuate the exacerbation of fatigue following exercise for patients with CFS. This opens up the possibility of greater progression in GET and, therefore, potentially further increases in physical function. However, before a training study is undertaken a systematic evaluation of the acute response of the post-exertional exacerbation of fatigue and symptoms following modafinil is warranted. It is hypothesized that for modafinil compared to placebo, patients will report a lower RPE during exercise and less post-exertional exacerbation of fatigue. The protocol will involve two sessions of a six-day assessment period, each including a 48 hour pre-exercise baseline assessment and 96 hour post-exercise assessment. Each participant (n=20) will be asked to complete two exercise sessions (one with modafinil and one with placebo) separated by at least two weeks. The order of the treatment trial (placebo or modafinil) will be randomised and counter-balanced as well as double-blinded. The exercise bout will consist of moderate-intensity cycling for generally 20 minutes.

One-third of youth presenting to GPs and paediatricians complain of physical/somatic problems (e.g., recurring headaches, stomach-aches) that have no physical cause. These complaints are termed functional somatic syndromes (FSS). Importantly, up to 80% of youth with FSS also experience emotional disorders. However, to date, FSS interventions have solely focused on pain management, whilst overlooking the co-occurring anxiety and depressive disturbances. This is problematic given these children are at high-risk for experiencing chronic psychopathology into adulthood. The aim of this RCT is to test the efficacy of the CoolKids and Adolescent Health (psychological therapy) program which is a newly developed program specifically tailored for distressed children (7-17 years) struggling to cope with somatic-health complaints. Given the CoolKids and Adolescent Health program is also designed to concurrently manage both somatic and anxiety/depression symptoms, it is hypothesized that this program is expected to: i) lead to significant reductions in somatic, anxiety and depressive symptoms and improvement in quality-of-life compared to a wait-list control group. ii) The effects will be retained at 6-months and 9-months follow-up.