East Meadows, New York
Aquatic and Land Exercises for Chronic Low Back Pain
Phase
N/ASpan
56 weeksSponsor
University of EdinburghEdinburgh
Recruiting
Development and Validation of a New Paediatric Inflammatory Bowel Disease NUTrition Risk Score (PIBD-NUTS)
Phase
N/ASpan
133 weeksSponsor
University of GlasgowEdinburgh
Recruiting
MEMRI and Kidney Disease
Phase
N/ASpan
261 weeksSponsor
University of EdinburghEdinburgh
Recruiting
Sotagliflozin in Patients With Heart Failure Symptoms and Type 1 Diabetes
BACKGROUND Intensive insulin therapy designed to near-normalize glucose levels in people with type 1 diabetes significantly reduces an individual's risk of long-term micro- and macrovascular complications. Unfortunately, glycaemic targets are not achieved by the majority of people with type 1 diabetes and as such overall life expectancy remains reduced compared to those without type 1 diabetes. Cardiovascular disease remains a major cause of morbidity and mortality in type 1 diabetes. There is growing recognition that heart failure (HF) is an increasing problem in type 1 diabetes. Diabetes itself is an independent risk factor for HF, causing structural and functional cardiac changes that predispose to HF (known as diabetic cardiomyopathy). HF is the end result of many cardiovascular diseases such as hypertension and myocardial infarction, and improved treatments for these conditions and changing demographic trends mean that many more people are surviving longer and developing HF. HF has a substantial healthcare burden. In the United States (US) and Europe, the prevalence of HF in the general population is around 1-2% - around 6 million adults in the US are estimated to be living with HF currently. In 2014 in the US there were ~1.1 million emergency department visits, 980 000 hospitalizations, and 84 000 deaths with HF as the primary cause, with an estimated cost of ~$11.3 billion (~$11,500/per patient for each hospitalisation). Despite advances in management of HF over the past 30 years, the incidence of mortality and HF hospitalisation in recent HF clinical trials remained high at ~20-30% over 2 years. The burden of HF in type 1 diabetes is less well characterised compared to HF in those with type 2 diabetes (and individuals without diabetes), however the data still indicate the substantial nature of this growing problem. One of the largest epidemiological studies was a Scottish national data study of 3.25 million individuals >30 years old, where the crude incidence of HF hospitalisation was over twice that of the population without diabetes. While the crude incidence was less than in type 2 diabetes, type 1 diabetes patients were on average 20 years younger. Despite their younger age, 30-day mortality following HF hospitalisation was higher in individuals with type 1 diabetes after adjustment for age, sex and socioeconomic status, indicating that outcomes are worse in HF patients with type 1 diabetes compared to those with either type 2 diabetes or without diabetes. Data from Scandinavia supports this finding and suggests that the risk of both incident HF and cardiovascular mortality was higher for individuals with type 1 diabetes compared to type 2 diabetes after adjustment for age. The overall prevalence of HF in this study at baseline was 3.1% - extrapolated to the US this would equate to 57,000 of the 1.9 million individuals with type 1 diabetes. A recent meta-analysis of all available data suggested that the incidence of HF was 3.1 times higher in individuals with type 1 diabetes compared to controls (typically the general population). Assuming a 5% incidence of HF hospitalisation/year, HF hospitalizations cost the US healthcare system ~$29 million per year. In summary, these data suggest that not only is HF a significant problem in individuals with type 1 diabetes, but there is evidence of an outcome disparity compared to individuals with type 2 diabetes or those without diabetes. Although there are some differences (e.g. presentation at a younger age), the pathophysiology of HF in type 1 diabetes is similar to type 2 diabetes. Risk factors are similar (e.g. glycaemic control, coronary artery disease and hypertension), leading to inflammation, endothelial dysfunction, fibrosis, and subsequent diastolic and systolic dysfunction. Given the pathophysiological similarities, there is little to suggest that HF therapies that have shown benefit in individuals with type 2 diabetes (or individuals without diabetes) would not also be efficacious in type 1 diabetes. In all current HF guidelines mainstay HF treatments (renin-angiotensin system blockers, beta-blockers, and mineralocorticoid receptor antagonists) are recommended for all patients with HF regardless of diabetes status. Sodium-glucose co-transporter inhibitors (SGLTi) were initially developed as oral add-on treatments for glycaemic control in type 2 diabetes. A consistent finding in large cardiovascular outcome trials was a significant ~30% risk reduction in hospitalisation for HF, as well as overall reductions in cardiovascular mortality. Subsequently, SGLTi in addition to guideline-directed HF therapy have been studied in HF patients either with type 2 diabetes or without diabetes and have again shown a consistent benefit compared to placebo, with significant reductions in mortality and HF hospitalisation irrespective of cardiac function left ventricular ejection fraction (LVEF) at baseline without any concerning safety signals. SGLTi also improve HF-related quality of life (QoL) and renal outcomes. This has led to the inclusion of SGLTi in the most recent HF treatment guidelines as a cornerstone of therapy in addition to established pharmacological agents (e.g., renin-angiotensin system inhibitors, beta-blockers and mineralocorticoid receptor antagonists). However, there is one key issue - individuals with type 1 diabetes have been excluded from these HF trials, in part due to concerns around safety. At present there is no evidence to support the use of these life-saving therapies in this population that already has worse outcomes than other groups with HF. In adult type 1 diabetes, Phase III trials with dapagliflozin, empagliflozin and sotagliflozin have been completed, collectively showing modest benefits of SGLT inhibition in terms of Haemoglobin A1c (HbA1c) reduction, increased time in range, reduced body weight and total insulin dose. However, SGLTi use in type 1 diabetes was also associated with an increased risk of diabetic ketoacidosis (DKA), which has limited their more widespread use in type 1 diabetes. Sotagliflozin is a dual SGLT1 and 2 inhibitor that is currently approved in the United Kingdom for use in individuals with type 1 diabetes with a body mass index (BMI) of ≥27kg/m2 and taking insulin doses of at least 0.5 units/kg of body weight in patients with inadequate glycaemic control. As with selective SGLT2i, sotagliflozin also improves HF-related outcomes. The key evidence for this comes from two clinical trials. In the Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease (SCORED) trial including 10,584 patients with type 2 diabetes, chronic kidney disease and cardiovascular risk factors, sotagliflozin caused a 26% relative risk reduction in the primary endpoint of cardiovascular death, HF hospitalisation or urgent HF visit compared to placebo. There was also a 33% relative risk reduction in HF hospitalisation or urgent HF visits, figures consistent with other SGLT2i trials. The second key trial was the Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure (SOLOIST-WHF) trial. In this trial 1,222 patients with type 2 diabetes and a recent HF hospitalisation were randomised to sotagliflozin 200mg once daily (with uptitration to 400mg once daily) or placebo. Patients were included regardless of left ventricular ejection fraction (LVEF) at baseline. The median follow-up duration was 9 months. Sotagliflozin caused a 33% relative risk reduction in the primary outcome of cardiovascular death, HF hospitalisation or urgent HF visit, with a 36% reduction in HF hospitalisation or urgent HF visits that met statistical significance. Sotagliflozin also significantly improved QoL at 4 months measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ). Rates of serious adverse events (SAEs) leading to study drug withdrawal were similar in both sotagliflozin and placebo groups, though severe hypoglycaemia was more common with sotagliflozin than placebo (9 individuals vs. 2). There was no significant increase in incidence of DKA with sotagliflozin compared to placebo (2 vs. 4). Taken together, these two trials confirm the benefit of sotagliflozin on HF related outcomes, consistent with selective SGLT2i. Again, individuals with type 1 diabetes were excluded from both of these trials. In summary, there is significant HF related morbidity and mortality in type 1 diabetes, and outcomes are worse than in HF patients with type 2 diabetes or without diabetes. Oral sotagliflozin 200mg daily is licensed for improving glycaemic control in type 1 diabetes in the UK. Although sotagliflozin improves HF related outcomes and QoL in patients with type 2 diabetes and patients with HF who do not have diabetes, studies are needed to determine whether these benefits might extend to patients with type 1 diabetes and heart failure. RATIONALE As outlined above, HF is a significant problem in type 1 diabetes, with an estimated prevalence of 3-5%. Outcomes for individuals with type 1 diabetes and HF are worse than in those with type 2 diabetes or without diabetes, with increased mortality and hospitalisation rates. Critically, patients with type 1 diabetes have been excluded from pivotal trials of the latest advance in HF treatment (SGLT2i), potentially exacerbating these outcome disparities further. The proposed trial will be the first to provide data on the efficacy and safety of sotagliflozin, in patients with type 1 diabetes and HF (regardless of LVEF). If a beneficial signal is found, this would provide strong support for extending the use of sotagliflozin in this group of patients with type 1 diabetes and adoption into clinical guidelines. A multi-centre, double-blind, randomised controlled trial to provide the strongest level of evidence for previous findings of the researchers will be conducted. Importantly, by choosing QoL measured using the KCCQ as the primary endpoint, an outcome that not only correlates strongly with mortality and hospitalisation but is also accepted by the US Food and Drug Administration (FDA) as a valid endpoint for regulatory approval has been selected. The KCCQ is a 23- item self-administered questionnaire that measures the patient's perception of their health status, including HF symptoms, impact on physical and social function, and how their HF impacts their QOL within the preceding 2 weeks. Improvements in KCCQ score map very well to reductions in mortality and hospitalisation and SGLT2i have consistently improved KCCQ scores. A 5-point increase in KCCQ score is traditionally considered clinically meaningful and is associated with a 7% reduction in mortality and HF hospitalisation. Given the prohibitive size of trial that would be required to demonstrate an improvement in mortality or HF hospitalizations with sotagliflozin in type 1 diabetes, the KCCQ represents an ideal endpoint for the trial. The proposed trial has the potential to be a high-impact, practice-changing trial.
Phase
2Span
74 weeksSponsor
University of DundeeEdinburgh
Recruiting
Digital App for Speech & Health Monitoring
This project aims to create novel speech-based solutions for: 1) Early detection, 2) Monitoring and 3) Stratification of neurodegenerative disorders including dementia, motor neuron disease (MND), Parkinson's disease (PD), and multiple sclerosis(MS). The investigators will develop and validate proof of concept and early-stage algorithms derived from acoustic data, which will be scaled and tested in deeply-phenotyped population. 2.2 Objectives Primary Objectives 1. To deploy and iterate a digital platform, co-produced with people living with neurodegenerative disorders, for acquisition of speech data from well characterised cohorts of people living with neurodegenerative disorders (dementia, motor neuron disease, multiple sclerosis, Parkinson's disease), and a healthy control cohort (comprising relatives/carers and volunteers without a neurological diagnosis), linked to our highly curated clinical registries at the Anne Rowling Regenerative Neurology Clinic. 2. To collect a large body of acoustic speech data from well characterised cohorts of people living with neurodegenerative disorders (dementia, MND/ALS, multiple sclerosis, Parkinson's disease), and a healthy control cohort (comprising relatives/carers and volunteers without a neurological diagnosis), linked to highly curated clinical registries. 3. To apply machine learning approaches directly to acoustic and linguistic signals from voices from people with dementia, MND, MS, Parkinson's, and healthy controls (comprising relatives/carers and volunteers without a neurological diagnosis), and to characterise prosodic patterns (rhythm, intonation, and fluency) without explicit reference to the text which is spoken, providing powerful cues about the health of the speaker. 4. Compare speech based digital outcome measures to current clinical standards to characterise and validate their clinimetric properties. Secondary Objectives 1. Assess the feasibility and acceptability of a digital outcome measure platform in people living with neurodegenerative conditions, for use in clinical care and research. 2. To create a repository of well characterised acoustic voice samples for open access sharing/collaboration with research and industry partners.
Phase
N/ASpan
103 weeksSponsor
University of EdinburghEdinburgh
Recruiting
Healthy Volunteers
Visual Frailty in Ageing
This is a mixed methods observational cross-sectional study that will consist of designing a tool to measure visual frailty and piloting it in a cohort of participants in the ageing population. The study will be implemented over a period of three years: literature review to define visual frailty and designing of the tool in the first year, recruitment of participants and performing a pilot and a validation study in the second year and thesis write-up in the final year. Participants aged 60 and above with a known diagnosis of advanced Age-related Macular Degeneration (AMD) will be recruited from Princess Alexandra Eye Pavilion (PAEP) macular clinic, Anne Rowling Clinic which is hosting the NHS Low Visual Aid Clinic, or any other NHS Lothian facility treating patients with Age-related Macular Degeneration (AMD). The visual frailty index will consist of results from visual acuity, reading performance, functional status, mental health and co-morbidities. This tool will be piloted in a cohort of 20 patients with advanced AMD. The internal consistency of the tool will be determined at this phase of the project. In addition to visual frailty, physical frailty will also be assessed in this cohort to enable analysis and establishment of the relationship between the two. The patients with AMD and their relatives/carers will be invited to participate in remote data collection about their perspectives on visual frailty. Best corrected distance and near visual acuity will be assessed and recorded. Reading performance will consist of reading speed and reading acuity which will be automatically measured using Digital Radner that will be acquired and installed before the implementation of the study. Functional status will be assessed using Lawton and Brody Instrumental Activities of Daily Living (IADL) Scale. Mental health will consist of depression, anxiety, and cognitive impairment that will be assessed using General Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and Six-item Cognitive Impairment Test (6-CIT) respectively. All these are validated tools. Physical frailty will be assessed using the FRAIL scale which relies on functions of fatigue, resistance, ambulation, illnesses and loss of weight. Information about co-morbidities will be retrieved from the patients' health record through National Health Service (NHS) Lothian. The data to be collected remotely from both the patients and their relatives/carers will be done through a phone call which will be scheduled during the hospital appointment. These calls will be recorded for analysis. They will then be transcribed verbatim, coded, and themes will be generated during the analysis. In addition to defining and designing a tool to measure visual frailty, expert input will be sought from optometrists and ophthalmologists about this topic using an online survey.
Phase
N/ASpan
47 weeksSponsor
University of EdinburghEdinburgh
Recruiting
Healthy Volunteers
First-in-human Study of CRB-601-01 to Treat Patients with Advanced Solid Tumor.
CRB-601-01 is a three-part interventional study which aims to: - To determine the maximum tolerated dose (MTD) and pharmacologically active dose range (PADR) for CRB-601 administered as a monotherapy in patients with select relapsed/refractory solid tumors who have progressed after at least one line of therapy - To determine the optimized dose for CRB-601 when administered within the PADR in combination with anti-programmed (cell) death ligand 1 (anti-PD-(L)1) therapy ( in patients with select relapsed/refractory solid tumors who have progressed after at least one line of therapy - To determine the optimized dose for CRB-601 when administered within the PADR in combination with anti-PD(L)-1 therapy and single-lesion, immune-priming stereotactic body radiation therapy (SBRT) in patients with select relapsed/refractory solid tumors who have progressed after at least one line of therapy The study will be run in 3 parts (A-C), run sequentially. Part A Dose Escalation Part A is designed to evaluate the safety, tolerability, and determine the MTD of CRB-601 administered as monotherapy in participants with select relapsed/refractory solid tumors that are known to express avb8 integrin. All participants will have had disease progression (PD) after at least one line of therapy or have no other standard therapy of proven clinical benefit currently available or be recommended based on the investigator's individual risk-benefit assessment for the participant. In Part A, doses will be escalated following the standard Bayesian Optimal Interval Design (BOIN) to determine the MTD and PADR or CRB-601. Three (3) dose groups treated on a 28 cycle with dosing every 2 weeks (Q2W) are predetermined. The target toxicity level is 0.3, the maximum number of participants that can be enrolled at each dose level is 12 participants and the maximum sample size of the BOIN design is 36. Determination of dose-limiting toxicities (DLT) will be based on toxicities observed during the DLT observation period (first 28-days or Cycle 1). Dose escalation /de-escalation decisions are made on the basis of occurrence of DLT. Part B Combination Safety Lead-in and Signal Seeking Part B is designed to assess the safety and tolerability of CRB-601 combined with anti-PD(L)-1 therapy, with or without single-lesion, immune-priming SBRT. There will be two distinct phases to Part B, a safety lead-in phase with a two-step dose-escalation and an Expansion Phase to seek efficacy signals in select solid tumors. The following cohorts will be initiated: Safety Lead-in - A cohort of 20 participants with select tumor-types (10 participants at a low-dose, and 10 participants at a high-dose, as selected in Part A) in combination with anti-PD(L)-1 at the recommended dose and schedule. - A second cohort of 20 participants will be treated with CRB-601 (10 participants at a low dose and 10 participants at a high-dose), in combination with anti-PD(L)-1 at the recommended dose and schedule and single-lesion, immune-priming SBRT Additional participants with select tumor-types showing preliminary efficacy will be enrolled in an expansions phase. Part C Dose Optimization Part C will follow a time-to-event Bayesian optimal Phase 2 (TOP Bayesian) study design developed for cancer immunotherapy. The aim of dose optimization is to determine the recommended Phase 2 dose (RP2D) by evaluating the efficacy of CRB-601 in combination with anti-PD(L)-1, with or without single-lesion, immune-priming SBRT (in terms of objective response rate [ORR]) when administered at two dose levels in a tumor-type selected based on preliminary efficacy observed in Part A and B. Participants will be randomized into one of two dose levels (low-dose CRB-601 group and high-dose CRB- 601 group) of 12-20 participants. In each arm, eligible participants will receive CRB-601 in combination with anti-PD(L)-1, with or without single lesion, immune priming SBRT (should the risk/benefit of immune-priming be established in Part B) and be monitored for safety and efficacy. For all enrolled participants (Parts A to C), study intervention will continue until any of the pre-defined criteria for discontinuation of study intervention are met, including intolerable toxicity, death, withdrawal of consent for study intervention, start of a new anti-cancer therapy, or investigator determined PD according to RECIST 1.1 or symptomatic deterioration attributed to PD. General In all parts, tumor response will be evaluated by the investigator according to RECIST v1.. During the post-treatment follow-up period, only participants who had discontinued study intervention for reasons other than PD or start of a new anti-cancer therapy (e.g., due to toxicity) will undergo tumor assessments. In these participants, tumor assessments will continue until death, confirmed radiographic PD according to RECIST v1.1, symptomatic deterioration attributed to PD, initiation of a subsequent anti cancer therapy, withdrawal of consent for the study or any of the other pre defined criteria for withdrawal from the study are met, whichever occurs first. All discontinued participants (with the exception of the reason of death) will be followed for 3 months for immune-related adverse events (irAEs) unless consent is refused in writing by the participant. Lesions selected for single lesion, immune priming SBRT or on-treatment biopsy, will be omitted from tumor assessments by RECIST v1.1. Clinical and laboratory adverse events (AEs) will be reported and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. Guidelines for dose interruptions (e.g., for toxicity) are included in the protocol. Biomarkers will also be measured. Collection of off- and on-treatment biopsies in Parts A to C are considered mandatory, unless agreed with the sponsor. Fresh tumor biopsies or archival tumor formalin fixed paraffin embedded (FFPE) samples are acceptable for baseline evaluation, and on-treatment samples will be collected on C2D15. Blood samples for biomarker and cytokine/chemokine assessments will also be collected.
Phase
1/2Span
104 weeksSponsor
Corbus Pharmaceuticals Inc.Edinburgh
Recruiting
Examining Scottish Chiropractic Professional Identity Using Chiropractic Professional Identity Scales
Research Question(s) Using the CPIES and CPISOS, does the strength of chiropractic professional identity (CPI) vary across Scottish chiropractors? For the CPIES and CPISOS, are there any influences on CPI across age, gender, ethnicity, or pre-professional educational variables? Rationale and Significance of the Study By aiming to understand CPI and its drivers, the investigators may be able to strengthen and develop chiropractors' professional identity without homogenisation. A strong professional identity facilitates the taking up of professional responsibilities, promotes a sense of belonging and professional socialisation, increases competence, fosters greater belonging, stability, and esteem, and promotes enhanced decision-making and confidence. These have been shown to enhance trust and patient safety and ultimately lead to better practice and patient outcomes. By better understanding CPI, and through the use of the Chiropractic Professional Identity Embodiment Scale (CPIES) and the Subtype Orientation Scale (CPISOS), the investigators may be able to identify potential divisions or areas of friction in chiropractic curriculum and to better support the profession. Chiropractic research has shown that burnout and professional dissatisfaction may be a consequence of poor professional identity. In a sample of chiropractors, the CPIES and CPISOS may help to identify areas of professional identity that could be strengthened, and that may ultimately improve professional satisfaction and success. This project will also allow us to collect demographic data of Scottish chiropractors, which may also assist in understanding the profession in greater detail and depth. Literature/Past Research Review Simply belonging to a profession does not alone determine one's professional identity; rather, variation exists in beliefs relating to one's occupation. 11 While chiropractic is an established health profession, there is a lack of clarity about the role of chiropractic in healthcare. There is disagreement on what characterises the chiropractic profession, its philosophy, and scope of practice. Chiropractors themselves have reported being challenged at times by the unclear public identity of the profession brought about by contrasting practice styles. Studies exist on chiropractors' attitudes and beliefs on professional identity. In North America, New Zealand, and Australia, pre-chiropractic education and the geographic region have been shown to be associated with differences in professional identity. In North America, chiropractic students report a preference for participating in mainstream health care and a desire to hold to traditional chiropractic theories and practices, being elements of various domains of chiropractic professional identity. Professional identity has been said to begin with formal education and has been researched with undergraduate chiropractic students. Common themes of an interplay between professional association membership status, pre-chiropractic education, and institutional philosophy have been cited as being determining factors in identity construction. Limitations of these current studies exist, the main being that the surveys employed in the research were not psychometrically validated. Additionally, the surveys differed in each study, making generalisability and comparisons difficult. These issues may be remedied through the use of a consistent psychometrically robust scale such as the CPIES. The CPIES was derived through mixed methods research using a qualitative phase that used one-to-one cognitive interviews of 15 expert key informants to inform and develop a pool of 92-candidate items across six known CPI domains. These items were then tested on 231-participants (New Zealand chiropractors and chiropractic students) for psychometric robustness. The final CPIES comprised 22-items and was found to be a valid and reliable measure of CPI. It has been identified that further research is needed to improve the understanding of measurement properties of tools used in research and to aid their selection and use. 25, and this research aims to begin to fill some of these gaps in knowledge. Primary research question: Using the Chiropractic Professional Identity Embodiment Scale (CPIES) and Subtype Orientation Scale (CPISOS), does the strength of chiropractic professional identity (CPI) vary across Scottish chiropractors? Secondary research question: For the Chiropractic Professional Identity Embodiment Scale (CPIES) and Subtype Orientation Scale (CPISOS), are there any influences on chiropractic professional identity (CPI) across age, gender, ethnicity, or pre-professional educational variables? Design of the Study Study design and setting This research is quantitative descriptive study to analyse CPIES and CPISOS questionnaire data across Scottish chiropractors and chiropractic students. The study will be conducted primarily at the Scotland College of Chiropractic. The lead investigator for the project is Dr Alice Cade. Participants All practising Scottish chiropractors and currently enrolled chiropractic students will be invited to take part in this study. Potential participants will not be eligible if they are practising outside of Scotland or enrolled to study chiropractic in an institute outside of Scotland. Procedure Participants will be asked to review the purpose of this study and the participant selection criteria, indicate their agreement to participate, and complete an online web-based survey to rate their beliefs towards 22-CPIES and 21-CPISOS statements and one CPI self-categorisation question on a 5-point Likert scale. The survey is anticipated to take 10 minutes to complete. Data will be anonymous and collected on a platform such as Qualtrics to be analysed by R software. The sample size was based on calculations recommended by Bartlett (2001), where the alpha level a priori at .05, and based on a five-point scale, the level of acceptable error at 3%, and estimated the standard deviation of the scale was 1.25. As the sample size calculated exceeded 5% of the possible population, the available sample size was corrected using Cochran's (1977) formula, resulting in a recommended sample size of 78. There are approximately 90 practising chiropractors and 26 students enrolled at the Scotland College of Chiropractic, and the investigators hope to gain a response from over half of these potential participants, which previous studies have found achievable. Statistical analyses Primary outcomes: A unidimensional score and six sub-scale numerical scores from the Chiropractic Professional Identity Embodiment Scale (CPIES). Secondary outcomes: A unidimensional measurement of chiropractic practitioner subtypes numerical score from the Chiropractic Professional Identity Subtype Orientation Scale (CPISOS). A numerical score from the self-categorisation of chiropractors' professional identity along a philosophical continuum scale. Demographical details will be analysed through descriptive statistics. Pragmatic use of additional statistical analyses between year groups for the CPIES and CPISOS will be used, and various correlations will be investigated for subscale and sum scores. Location The data will be collected online, and the research will be hosted by the Scotland College of Chiropractic.
Phase
N/ASpan
32 weeksSponsor
Scotland College of ChiropracticEdinburgh
Recruiting
Healthy Volunteers
Does Stress Change EEG Measures in Students: A Feasibility Study
The study's primary aim is to assess the feasibility of a more extensive future study. The investigators also hypothesise that as the semester progresses, participants will exhibit changes in their EEG outcomes that may be related to longitudinal or direct stressors. Study design and setting This study will be an observational study with a stress-related questionnaire (Depression, Anxiety, and Stress Scale - 21 (DASS-21)) over three time-points. Participants The investigators aim to recruit 10 participants and assess them three times over the course of their semester, early, middle, and late semester, with at least a four-week gap between each data collection. The investigators aim to recruit only healthy Scottish chiropractic students with no prior diagnosed mental disorder and who are capable of understanding the study procedure. Procedure Following screening for eligibility and consent, i.e., visit one (baseline), participants will be asked to answer a questionnaire and undergo EEG measurement and Montreal imaging stress task (MIST). The same EEG and questionnaire procedure will be performed in the remaining two data collection sessions. Each EEG recording session, with the participant seated, will consist of a two-minute resting state with the eyes closed for a baseline relaxation level among the participants. A following two-minute eyes-open phase will take place. After which, participants will be asked to perform the experimental phase of the MIST task, a following two-minute recording phase will be with the eyes open, and a final two-minute resting phase with eyes closed will conclude the task. The investigators aim to conclude the data collection around 16 weeks after the initial participant is recruited.
Phase
N/ASpan
33 weeksSponsor
Scotland College of ChiropracticEdinburgh
Recruiting
Healthy Volunteers
Single-Cell Sequencing Analysis of Radiation Pneumonitis Signals In Patients Treated For Cancer With Radiotherapy
Lung cancer is the third most common cancer in the UK with around 48,500 people diagnosed with the condition each year. Unfortunately, despite significant progress in treatment options and their delivery, improvements in survival remain elusive. Radiotherapy (RT) is a cornerstone of both radical and palliative treatment in non-small cell lung cancer (NSCLC). Radiation pneumonitis (RP) is the key dose-limiting constraint and a morbid, potentially even life-threatening, toxicity associated with RT to the thorax. Newer combinations of chemo-radiotherapy and adjuvant immunotherapy demonstrate improved survival but are associated with higher risk of RP. Current management of RP is very limited consisting of supportive measures and steroids; the latter of which are often ineffective and come with their own risks. The typical triad of symptoms (exertional dyspnoea, a non-productive cough and hypoxia) can be directly fatal for some whilst for others represent a devastating and permanent decline in their lung function and quality of life. Although modest understanding of the patient and treatment related risk factors for RP development have been identified the underlying mechanisms remain poorly understood and has been challenging to investigate. A cascade of inflammatory changes with hypoxia lead to endovascular damage, cytokine release and ultimately endothelial cell death and irreversible fibrosis. Single-cell RNA sequencing (scRNA-seq) is a relatively novel technique that allows access to an understanding of this process. It can allow the identification of what genetics, cell types and functional heterogeneity are up/down-regulated in association with irradiated lung tissue in humans. It is known that Stereotactic-Ablative Radiotherapy (SABR) is a well-tolerated highly conformal form of RT. It has been safely delivered to patients before radical surgery without significant toxicity or increase in complication rate. If a targetable mechanism behind this condition could be identified it has the potential to change the landscape of lung cancer RT management and in doing so save lives. A literature search revealed no investigation like this has been conducted in humans. A Chinese study has been done in murine models and demonstrated several signals which, if demonstrated in humans, could be of interest. SPITFIRE proposes to obtain inflamed lung tissue from patients who have developed pneumonitis following radiation for their lung cancer to find these answers. 1.2 RATIONALE FOR STUDY Both patients who have potentially been cured of their lung cancer and those being treated to alleviate symptoms in their last months-to-years of life are diagnosed with RP. Potentially treatable disease can be refused due to an unacceptable combination of risk factors for developing RP. Hospitalisation for RP is common and yet often frustratingly unhelpful. RP is a major contributor to patient morbidity, mortality and healthcare cost. Although clearly a constant concern in lung cancer any radiation delivered through the chest (including oesophageal, breast and pulmonary metastatic RT) carries a risk of RP. Pulmonary fibrosis treatment is starting to improve with novel agents such as Nintedanib and Pirfenidone demonstrating some promise. There is likely, though yet unproven, crossover between the molecular and genetic processes involved in these conditions. Should a better understanding of the mechanisms behind RP reveal a targetable signal, and subsequent treatment, it has the potential to completely change not only the management of this toxicity but that of thoracic malignancies. Obtaining tissue from human lung affected by RP is a challenge. These patients are often too unstable to safely proceed with such intervention. There is, however, a population of patients who have clinical and radiological features diagnostic of the condition but maintain oxygen saturations (SpO2) adequate to proceed to bronchoscopy. Some of these patients will be referred for a bronchoscopy to exclude super-added infection. As part of this process they may be enrolled in the ELFMAN (Edinburgh Lung Fibrosis Molecular Endotyping) Study - to better characterise suspected inflammatory and fibrotic interstitial lung disease, as it may have shared molecular pathways to interstitial pneumonias including idiopathic pulmonary fibrosis (IPF). Standard bronchoscopy may not reach the effect area of lung but deep bronchial brushings obtains a good cellular yield which should be adequate for scRNA-seq whilst minimising risk to the patient. This study proposes to utilise a brushing from these patients to process using a novel laboratory technique to help identify the cellular processes that may be involved in radiation pneumonitis.
Phase
N/ASpan
62 weeksSponsor
NHS LothianEdinburgh
Recruiting