2020.004
F7ICH-1371, F7ICH-1641
There is a known association between levels of GFAP on admission and the volume of spontaneous intracerebral hemorrhage. However, the relationship between GFAP and intraventricular hemorrhage, a dangerous complication of spontaneous intracerebral hemorrhage, has not been studied. We will test the association between admission levels of GFAP and the presence of IVH while accounting for demographic and clinical patient attributes. We hope that this research will provide a reliable method for predicting the presence of IVH as early in the hospitalization as possible.
2020.003
F7ICH-1641
We propose using a personalized approach to prognostication after hemorrhagic stroke. By using statistical modeling, we can accurately predict how well an individual patient will recover, which is critical information for both the patient, caregivers, and physicians.
2020.002
NN1250-1876, NN1250-1987, NN1250-1988, NN1250-1989, NN1250-1990, NN1250-1991, NN1250-1992, NN1250-1993, NN1250-1994, NN1250-1995, NN1250-1996, NN1250-3538, NN1250-3678,NN1250-3762, NN1250-3769, NN1250-3999, NN1250-4000, NN1250-4227, NN5401-1719, NN5401-1738, NN5401-1740, NN5401-1788, NN5401-1790, NN5401-1959, NN5401-1977, NN5401-1979,NN5401-1985, NN5401-3857, NN1218-3889, NN1218-3978
Clamp studies are used to investigate the action profile of insulins. One of the most common “adverse events” during clamp studies is headache. We want to characterize headaches occurring during clamp studies and understand how they are related to the glucose infusion rate which reflects the action profile of the insulins.
2020.001
F7ICH-1641
Intracerebral hemorrhage (ICH) is the most severe type of stroke and currently has no effective treatment. Anemia and lower hemoglobin levels constitute an appealing target in cardiovascular disease, with interventions already available. Previous studies have shown a relationship between lower hemoglobin levels and poor outcome after ICH. In our project, we aim to quantify this association and to determine the specific underlying mechanisms. This information can potentially guide our efforts to develop therapeutic interventions for this debilitating condition.
2019.003
EX2211-3748
Chronic kidney disease (CKD) is a significant global public health
problem, but the progression of CKD is often slow. There are few
specific symptoms until the person reaches the stage of kidney
failure. As such, the major challenge in identifying new treatments
for CKD are the expense and complexity of clinical trials given the
need for long duration of these trials to collect sufficient kidney
failure outcomes.
We aim to explore candidate surrogate
endpoints for clinical trials of drugs to slow the progression of
kidney disease. Our focus lies on using change in albuminuria (protein
in urine) and glomerular filtration rate (how well kidneys filter
blood) as early markers of chronic kidney disease. These can then be
used to design shorter and less expensive clinical trials that will
ultimately be able to treat chronic kidney disease. The proposed aims
represent further investigations on a past decade of work.
2019.001
EX2211-3748 NN9535-3744
Diabetes is a major health issue, affecting almost 425 million people worldwide. Type 2 diabetes accounts for about 90% of all diagnosed cases of diabetes in adults. Cardiovascular events, such as myocardial infarction or stroke, are considered as the foremost cause of death in patients with type 2 diabetes. Several glucose lowering drugs have shown efficacy to control chronic hyperglycemia. Recently marketed drugs, such as glucagon-like peptide-1 receptor agonist (GLP-1) and sodium glucose linked transporter-2 inhibitor (SGLT-2), have further shown efficacy to reduce cardiovascular events in type 2 diabetes. These results are derived from large, international clinical trials. In a preliminary analysis, we have shown that geographic variations might exist in these clinical trials, suggesting that benefit from these drugs might differ according to the region of the world. These differences, if they are confirmed, could be explained by different factors, such as genetic variations, differences in lifestyle and diet, or in background therapy. The primary objective of this study is to assess whether efficacy of GLP-1 analogs and SGLT-2 inhibitors on cardiovascular events is homogenous across the different regions of the world, and if not, to find the factors explaining such variability. More details about our objectives and methods are available on the PROSPERO registry https://www.crd.york.ac.uk/ prospero/display_record.php?RecordID=120221.
2018.004
NN1218-3854
Use of devices for continuous monitoring of the blood sugar is valuable for people with diabetes to understand their disease and to help prevent low blood sugar. Furthermore, continuous monitoring should be used in drug development to evaluate efficacy and safety. However, the devices have been criticised for being too inaccurate. This investigation seeks to reveal the inaccuracies of current devices and to assess the subsequent usability related to the mentioned use cases
2018.003
NN1250-3579
Identification of model parameters in Box-Jenkins and Stochastic Differential Equation. The models are to be used for designing optimal titration protocols for type 2 diabetic patients and should express the relation between insulin and blood glucose.
2018.002
EX2211-3748 (LEADER)
Short lay summary of the proposed research The applicants propose within the context of the Innovative Medicine Initiative BEAt-DKD (Novo Nordisk is an EFPIA partner in BEAt-DKD), to perform a post-hoc analysis of the LEADER trial. In the proposed analysis, the short term effects (± 6 months) of liraglutide on multiple renal and cardiovascular risk markers are assessed using individual data from the LEADER trial. The PRE score, a validated algorithm that translates the short term drug effect on multiple renal/cardiovascular risk markers into a predicted long term ((± 3-4 years) effect on renal/CV outcomes, will be applied on the observed short term risk marker changes in LEADER to predict the effect of liraglutide on renal outcomes.
2018.006
F7ICH-1371, F7ICH-1641
Intracerebral hemorrhage (ICH), bleeding into the brain from a ruptured blood vessel, is the deadliest type of stroke and has no effective treatments. We will investigate whether the location of the bleed in the brain, known to be associated with different underlying disease processes, modifies the effect of new treatments for ICH. Specifically, we will determine whether recombinant Factor VII treatment can reduce the amount of bleeding and swelling in the brain due to ICH in specific locations and improve outcomes.
2018.005
NN8022-1839
Individuals with overweight or obesity are at increased risk of type 2 diabetes mellitus (T2DM). A robust body of evidence is conclusive that weight loss is highly effective in preventing T2DM, yet weight loss is difficult to maintain with lifestyle interventions alone1. Treatment with once-daily subcutaneous liraglutide 3.0mg is a promising medication that provides sustained clinically relevant weight loss for 3 years2, and also may offer additional benefits in terms of reduced risk of T2DM.3 The ability to show links between exposure and bivariate outcome using logistic regression has limited power to show association.4 The CMDS score is classified based on bivariate criteria (i.e. you either have it or you don’t) according to National Cholesterol Education Program Adult Treatment Program III (ATP III) criteria.5 However, Metabolic Syndrome related risk for T2DM risk exists as a spectrum, and bivariate responses are not adequate to classify this range.6 This analysis uses a continuous cardiometabolic staging score (CMDS) system to assess the ability of liraglutide 3.0 mg to prevent T2DM and pre-diabetes as a function of the baseline CMDS score. The goal is to identify patients who are most likely to benefit from weight loss with the greatest benefit/risk ratio.
2018.001
NN7999-3747
NN7999-3639
Short lay summary of the proposed research The service will be a centralized, dedicated, web-accessible, actively moderated tool that allows the input of anonymized and certified hemophilia patient PK data. The service will provide expert validation of the estimation of the PK disposition of factor VIII/IX and report the results to the inputting physician. The service will facilitate the progressive accumulation of PK patient data which will be continuously enhanced by the data inputted into the system; thereby, allowing for progressive refinement of the knowledge of factor VIII and IX pharmacokinetics. The service will lead to a reduction in the need for blood plasma samples in individual patients. This should result in better care, intended both as more effective prophylaxis and optimization of resource utilization.
2017.004
F7ICH-1602
F7ICH-1371
F7ICH-2073
F7ICH-1389
F7ICH-1641
Short lay summary of the proposed research We know very little about how intracerebral hemorrhage affects the elderly. While what improves outcomes for younger people has been well documented little information exists concerning the elderly. We will describe this population looking for novel markers of improved outcome in elderly population. We hope this will lead to both improved manage of these elderly patients and novel therapeutic drug targets in intracerebral hemorrhage.
2017.001
NN304-1335
NN304-1708
NN304-1595
NN304-1448
NN304-1205
NN304-1430
NN304-1687
NN304-1316
NN304-1372
NN304-1447
NN304-1181
NN304-1243
NN304-1375
Short lay summary of the proposed research
Type 1 Diabetes Mellitus (T1DM) is a basal-bolus insulin regimen, for which two choices exist for basal insulin: long- and intermediate-acting insulin. These choices may have different risks of adverse events and effectiveness. To help patients and clinicians optimally select a basal insulin, knowledge regarding how the effectiveness of these agents differs across patient characteristics (eg, lifestyle, age, general health) is required. We aim to investigate the association between the individualized treatments for T1DM patients and A1C or severe hypoglycaemia. The results will be of interest to stakeholders and will help in improving existing guideline recommendations.
2017.005
INS-3966 (DAWN2)
Short lay summary of the proposed research People with a severe mental illness (SMI), e.g. schizophrenia or bipolar disorder, are almost three times more likely to have diabetes, and experience poorer health and healthcare than the general population. Diabetes has a major psychosocial impact, causing distress, poor quality of life and reduced capacity for self-management. People with SMI have additional psychological and social difficulties that are likely to increase their risk of diabetes distress and poor quality of life. However, very little is known about the impact of diabetes in this population. This study will explore the psychological and social impact of having diabetes alongside SMI and experience of diabetes healthcare. The aim is to increase understanding of how to improve diabetes care, including diabetes self-management for this vulnerable population. We will survey people with SMI and diabetes, their carers and healthcare professionals to examine the psychosocial impact of diabetes in SMI including diabetes distress, quality of life, and factors affecting diabetes self-management. Participants will be recruited through general practices and mental health services. We will compare findings with data from DAWN2, a global study of diabetes in the general population (http://www.dawnstudy.com/dawn2/about-dawn2.html). We will also test whether questions to measure diabetes distress and psychosocial impact are appropriate for people with SMI. Multi-stakeholder workshops will be used to discuss findings and identify opportunities to increase support for diabetes management. This study will provide insights on how diabetes can be managed more effectively for people with SMI. Study findings will be disseminated through our established research, clinical and service user networks to increase knowledge among clinicians and service providers, who sometimes make assumptions about why people with SMI experience poor diabetes outcomes (e.g. attributing blame to lifestyle and life choices). People with SMI and diabetes should experience better care, and improved physical and mental health outcomes as a result.
2016.001
NN8022-1807 NN8022-3970 NN8022-1923 NN8022-1839
Short lay summary of the proposed research The incidence of type 2 diabetes is increasing worldwide. It is currently unknown if dipeptidyl-peptidase (DPP)-4 inhibitors or glucagon-like peptide (GLP)-1 analogues could prevent or delay type 2 diabetes mellitus and its associated complications in persons at increased risk for the development of type 2 diabetes mellitus. We will identify all published and unpublished trials including participants with increased risk of type 2 diabetes comparing DDP-4 inhibitors or GLP-1 analogues with no intervention, placebo or other glucose-lowering drugs with a duration of 12 weeks or more. Data and bias assessment will be performed by two authors. Data will be combined through meta-analysis. The outcomes assessed will be all-cause mortality; incidence of type 2 diabetes; serious adverse events, cardiovascular mortality; non-fatal myocardial infarction; congestive heart failure; non-fatal stroke; amputation of lower extremity; blindness or severe vision loss; end-stage renal disease; non-serious adverse events; hypoglycaemia; health-related quality of life; time to progression to type 2 diabetes; measures of blood glucose control; socioeconomic effects.
2015.001
ANA-2023
nsulin pump therapy has proved to be useful in improving diabetes control in selected people with type 1 diabetes but there has been conflicting evidence to date for its effectiveness in type 2 diabetes. In order to identify if there are patient groups that benefit more than others from insulin pump treatment in type 2 diabetes, we now wish to combine the data from all published randomised controlled trials on changes in control during pump therapy compared to best injection therapy (a ‘meta-analysis’). Using advanced statistical techniques, we will analyse the effect of individual patient characteristics such as level of diabetes control at the start of the study (HbA1c), weight and insulin dosage on the effect of pump therapy on HbA1c, hypoglycaemia, insulin dose and weight change.
Diabetes Care. 2017 May;40(5):715-722. doi: 10.2337/dc16-2201. Glycemic Control During Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Insulin Injections in Type 2 Diabetes: Individual Patient Data Meta-analysis and Meta-regression of Randomized Controlled Trials. Pickup JC, Reznik Y, Sutton AJ
2015.002
NN7008-3893 NN7008-3522
Short lay summary of the proposed research The service will be a centralized, dedicated, web-accessible, actively moderated tool that allows the input of anonymized and certified haemophilia PK data. The service will provide expert validation of the estimation of the PK disposition of factor VIII/IX and report the results to the inputting physician. The service will facilitate the progressive accumulation of PK patient data which will be continuously enhanced by the data inputted into the system; thereby, allowing for progressive refinement of the knowledge of factor VIII and IX pharmacokinetics. The service will lead to a reduction in the need for blood plasma samples in individual patients. This should result in better care, intended both as more effective prophylaxis and optimization of resource utilization.
2014.001
NN1250-3579
The HbA1c test is a measure of diabetes glucose control over a 2 month period and may vary month by month depending on overall glucose control. We have shown for patients with type 1 diabetes that over the months those patients whose HbA1c remains steady have fewer diabetes related problems than those whose HbA1c varies. By looking at the data from the BEGIN once long study over a 12 month period, we can see if the HbA1c variability for one type of insulin (degludec) is less than for another (glargine) in type 2 diabetes. This may provide information on which to base a long term study in the future.