Clinical Research Directory

Hybrid Closed Loop Effectiveness Trial in Adults With Type 1 Diabetes

Minoritized individuals with type 1 diabetes (T1D) have approximately 2% higher average A1c levels and twice the rate of hospitalizations, complications, and mortality as their white counterparts. However, the efficacy trials establishing the benefits of hybrid closed loop (HCL) pump therapy in T1D have been in more socially advantaged and predominantly non-Hispanic white patients. Use of this technology by individuals with T1D from underserved communities remains very low. The investigators plan to conduct a randomized effectiveness trial - with broader eligibility criteria (including markedly elevated A1c) and longer follow up than the previous HCL efficacy trials - to evaluate the benefits, safety risks and treatment complications of HCL use in underserved adults with T1D. A comprehensive mixed-methods approach will be implemented to capture information about the user experience. Participants will be randomized (3:1 ratio) to one of three FDA-approved HCL systems or continuous glucose monitoring and multiple daily injection therapy. Subjects will be followed for 9 months to collect data on effectiveness (glucose % time-in-range 70-180 mg/dL and % time \< 70 mg/dL), safety (diabetic ketoacidosis and severe hypoglycemia events) and patient experience using the systems (including benefits and burdens, the impact of life stressors on HCL use, and how the match between HCL system functionality and the individual's needs and expectations impacts on user experience).

New Diagnostic Tool (MinION) for Identifying Microorganisms in Foot Wounds of Patients Living With Diabetic Foot Osteomyelitis

Diabetic foot wound infections are predominantly polymicrobial. However, 'conventional' microbiological culture does not identify all the bacteria potentially involved in these infections and requires time, which can have a negative impact by delaying treatment and/or the prescription of appropriate antibiotic therapy. Real-time metagenomics analysis using Oxford Nanopore Technologies' MinION technology has demonstrated sufficient power to identify virtually all microbial genomes in a given sample, providing additional information on their antibiotic resistance profile and in silico prediction of genes encoding virulence factors within than 4 hours. Based on these rapid results, a management protocol could be defined specifically for each patient with a view to personalised medicine. The aim is to study the diversity of bacterial and fungal species identified using the MinION method and compare this diversity with the results obtained using conventional methods (routine culture) from bone biopsies taken from DFOM patients.

Human iPSC for Repair of Vasodegenerative Vessels in Diabetic Retinopathy

This study proposes to carefully examine the hypothesis that human inducible pluripotent stem cells (iPSCs) can be effectively employed as a future therapeutic option for individuals with diabetic retinopathy and macular ischemia. iPSCs will be generated from the peripheral blood cells of subjects with diabetes and age matched controls. The human iPSC cells will be used to generate mesoderm cells for injection into the vitreous cavity of diabetic rodents and primate eyes. The ability of mesoderm cells to generate endothelial cells and pericytes in areas of degenerated capillaries will be examined. The human iPSCs will also be used to generate hematopoietic CD34+CD45+ cells. The combination of CD34+CD45+ cells derived from iPSCs and iPSC derived mesoderm will be examined in combination for their potentially beneficial effect to enhance the vessel formation.

Precision Subclassification of Mental Health in Diabetes: Digital Twins for Precision Mental Health to Track Subgroups

Mental conditions and disorders (e.g. distress, depressive, anxiety, and eating disorders) are more prevalent in people with diabetes (PWD) and associated with reduced quality of life and impaired glycaemic outcomes. Evidence supports a complex network between psychosocial factors and glycaemic control that can be highly variable between persons. It is assumed that subgroups exist that show different trajectories of glycaemia and mental health. Belonging to a particular subgroup may be linked with a higher risk of developing mental health problems compared to others. This suggests that it is possible to treat individuals in different subgroups in a manner that optimizes their treatment and can improve health outcomes. Accurate characterisation can inform more individualized care. This calls for a more personalised approach considering the idiosyncrasies of different subgroups. Over 3 years, the investigators have established the basis of a precision mental health approach for diabetes using n-of-1 analyses. By utilizing combined ecological momentary assessment (EMA: repeated daily sampling of psychosocial factors in everyday life) and continuous glucose monitoring (CGM), intensive longitudinal data per person could be collected. This enables the analysis of individual associations between glycaemic parameters and psychosocial variables and identification of individual sources of diabetes distress in each person. The objective of the present study is to use of the n-of-1 approach to identify subgroups of PWD who share common characteristics in the associations between glucose and psychosocial variables. The identified subgroups shall be used to develop a digital twin for precision mental health in diabetes. The digital twin serves as representation of a real person, allowing to make simulations and predictions of the course of mental health and glycaemia. These predictions can inform diabetes care and lead to more precise, personalised treatment decisions. To achieve this, a longitudinal panel including over 1,400 PWD who continuously complete EMA and questionnaire surveys and measure glucose levels using CGM was developed. Over 1000 clinical interviews to diagnose mental disorders have been conducted to identify major mental health conditions and map mental outcomes. To identify subgroups and develop the digital twin, the sampling will be expanded aiming at a total of 1,809 PWD. Incidence and remission of mental disorders will be determined via repeated interviews. The complex networks between clinical, metabolic, and psychosocial data will be analysed using machine learning, leading to new insights with the potential to shape future guidelines. These results will be used by the digital twin to predict courses of glycaemic control and mental health, translating the individual evidence into direct treatment suggestions.

Extreme Phenotypes to Identify Susceptibility of Patients Living With Type 2 to Diabetes Related Complications

The goal of this observational study is to learn more about the diverse susceptibility to micro and macrovascular complications in individuals living with Type 2 Diabetes (T2D). The main questions of the study are: * Is the chronic exposure to hyperglycemia the only determinant of diverse susceptibility to diabetes related complications (DRC) across the T2D population? * Is it possible to develop a reliable tool to identify patients at different susceptibility to DRC? * Is it possible to predict DRC susceptibility through biomarkers in the field of inflammation, hormonal signaling or non-coding circulating nucleotides. People living with T2D and well screened for complications according to the international recommendations (American Diabetes Association/European Society for the study of Diabetes) will be included in the survey collecting information about chronic exposure to hyperglycemia (diabetes duration + glycemic control) and incidence and severity of each macro and microvascular complication. Based on the survey result, a clinical score will be proposed to distinguish patient at different susceptibility to complications. Then, patients with extreme phenotypes of susceptibility (i.e. those with highest susceptibility for their short exposure to hyperglycemia vs those with lowest susceptibility to complication for their long exposure to hyperglycemia) will be recruited to perform a blood drawn and investigate whether preidentified potential biomarkers could describe the diverse susceptibility to DRC by showing a significant gradient between groups.

A Fruit and Vegetable Prescription Program

Dietary intake of fruits and vegetables (F\&V) is a cornerstone for the treatment of type 2 diabetes, however less than 16% of Hispanic adults consume the recommended number of servings each day. F\&V prescription (F\&V Rx) programs are embedded into clinical settings and provide patients with vouchers to purchase F\&V at local retailers. The proposed study aims to test the effects of a F\&V Rx on diabetes self-management education and support (DSME/S) uptake and retention, dietary intake of F\&V and diet quality, glucose control (hemoglobin A1c), and program implementation outcomes.

Thai PainPREDICT Validation Study

Painful diabetic neuropathy (PDN) is one of the most common and disabling complications of diabetes mellitus, substantially affecting quality of life, daily functioning, and health system burden. Early identification of PDN is crucial for timely treatment, prevention of complications such as foot ulcers and amputations, and for reducing healthcare costs. However, in Thailand there are limited culturally adapted and validated tools for screening PDN. PainPREDICT is an internationally validated questionnaire designed to characterize neuropathic pain profiles, but its adaptation for Thai patients has not yet been undertaken. In parallel, the use of mobile health technologies (mHealth) has the potential to expand access to screening and monitoring of chronic conditions, particularly in resource-limited settings.

Characteristics of Diabetic Foot Ulcer Patients

This study examines the demographic, clinical, and laboratory characteristics of patients with diabetic foot ulcers admitted to 5 Azar Hospital, Gorgan, in 2024. By analyzing factors such as Hb, WBC, HbA1C, ESR, and CRP in relation to ulcer severity, the study aims to identify predictors of outcomes and support more effective prevention and management strategies

Early Detection of Long-term Diabetic Complications in Children and Adolescents With Type 1 Diabetes

Aims: To investigate early markers of long-term diabetic complications and the association to an extended glucose metabolic profile comprising glucose control (current and past), glucose variability and insulin sensitivity in children and adolescents with type 1 diabetes (T1D). Background: Most Danish children and adolescents with T1D do not achieve their metabolic target and are at increased risk of developing long-term diabetic complications, reducing their life expectancy and increase their morbidity rate. Hence, improved metabolic control, a better understanding of what optimal metabolic control means, combined with detailed monitoring of the first markers of long-term complications and their reversibility or lack thereof are needed. Methods: A prospectivel study of 400 children, aged 6-18 years old, with T1D\>12 months. Early markers of long-term diabetic complications will be investigated as arterial stiffness, nerve dysfunction and nephropathy. Data on T1D onset, duration, treatment modality, self-monitoring-blood-glucose profiles, growth, weight, and pubertal status will be collected. Blood sampling will include routine tests and markers of glucose, lipid, bone, and gastrointestinal metabolism. DXA-scan, Fibroscan, bone-age, eye-examination and physical activity will be measured. Data on retrospective glucose- and lipid-profiles will be collected. The children will be offered a followup every 5 years for the next two decades. Perspectives: This study provides novel insight into the frequency of early markers of long-term diabetic complications and its association to the interplay of the pancreas, adipose, gastrointestinal and bone metabolic axis. Which can assist in identifying subgroups of children and adolescents requiring earlier in-depth screening for early markers of long-term diabetic complications, for putative interventions for prevention, hence reducing morbidity and mortality in T1D.

Gestational Diabetes Monitoring and Management

The primary goal is to predict the clinical outcomes of mother and baby using blood glucose and other routinely collected clinical data in pregnancy to predict adverse outcomes at birth in women with GDM. The secondary goal is to develop models to predict optimal blood glucose testing schedules for pregnant women. Exploratory Objectives are (1) to understand patterns of dosage and / or medication choice and (2) to describe different phenotypes of gestational diabetes based on multiple data input.

Electronic Diabetes Tune-Up Group (eDTU) for African Americans

The primary aims of this study are: 1. To test the acceptability and feasibility of the electronic DTU intervention (eDTU) that has been adapted for cultural relevance and online delivery compared to waitlist control and the in-person DTU (iDTU). The hypothesis is that the adapted intervention will be culturally acceptable (by participant satisfaction scores) and well-subscribed (intervention attendance rates). 2. To test differences in diabetes distress and A1c change scores between intervention (changes in T2 to T4) and waitlist control (change in T1 to T2) by intervention group (eDTU vs. waitlist control; iDTU vs. waitlist control). The hypothesis is that both the eDTU and iDTU groups will show significant improvements in diabetes distress and A1c compared to waitlist control. In order to conserve sample size and budget, participants in each intervention group will serve as their own waitlist control. Secondary Objective. The secondary aim of the study is to evaluate changes in depressive symptoms, diabetes self-efficacy, and general and diabetes-specific quality of life in intervention (T2-T3 \& T4) compared to waitlist control (T1-T2). An exploratory aim will be to compare changes in eDTU to the iDTU pre/post intervention (T2-T3 \& T4). The hypothesis is that both groups will show comparable improvements in diabetes distress and A1c.

Benefits of Insoles With Real-Time Alert and Foot Self-Care Education

Novel approaches to promote adherence to diabetic footwear and prevent high incidence of diabetes foot ulcers are urgently needed. Investigators propose to translate an innovative and practical technology to supplement clinical and risk evaluation for patients with diabetes through wearable insoles and smart watch, along with foot self-care education, to improve adherence to prescribed footwear and reduce incidence of foot ulcers in those with diabetes and at risk for foot ulcers.

Feasibility and Effectiveness of a Remote Monitoring Program for the Treatment of Diabetic Foot Ulcers

This research is being done to compare two different methods of wound monitoring for chronic wounds: remote wound monitoring using a smartphone app and in-person wound monitoring in a clinic setting. This will be a pilot non-blinded randomized controlled feasibility trial. The investigators will enroll 120 patients with an active diabetic foot ulcer (DFU) who present to the multidisciplinary diabetic foot clinic in Baltimore, Maryland. Patients will be computer randomized 1:1 to receive wound care monitoring using remote DFU monitoring technology or standard in-person monitoring for 12 weeks.

Efficacy of Adipose Tissue Derived Stem Cells for the Treatment of Diabetic Foot Ulcers

The aim of this study is to evaluate the therapeutic efficacy of uncultured adipose derived stromal vascular fraction (SVF) and cultured adipose derived stem cells (ASCs) both supplemented with platelet rich plasma (PRP) to treat chronic diabetic foot ulcers. It will increase the pragmatic potential of both types of cells as PRP is rich in survival and chemotactic factors. Moreover, the autologous nature of the proposed study will ensure safety of its use in diabetic patients and will unveil the more effective therapeutic option for treatment of foot ulcer wounds.

Clinical Trial Assessing Human Placental Membrane Products and Standard of Care Versus Standard of Care in Nonhealing DFUs and VLUs

The purpose of the study is to evaluate the efficacy of multiple human placental membrane products and Standard of Care (SOC) versus SOC alone in the management of nonhealing diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) over 12 weeks using a modified platform trial design.

The Effect of Roxadustat on Renal Oxygenation in Diabetes Nephropathy

The study will investigate if treatment with Roxadustat improves kidney oxygenation in diabetic patients with nephropathy receiving treatment for renal anemia, compared to patients receiving treatment with darbepoetin alpha. Participants will be randomized to either treatment, and receive equal care for renal anemia. Kidney oxygenation will be examined before treatment start and after 24 weeks using BOLD-MRI (blood oxygen level-defendant MRI), a non-invasive method available for measurement of tissue oxygenation levels that is comparable with direct invasive measurement of partial oxygen pressure. Blood and urin samples will be collected in connection to these visits. The primary endpoint is the change in medullary and cortical R2\* (inversely proportional to the tissue oxygenation content) after 24 weeks. Secondary endpoints will be albuminuria and urinary levels of ROS (evaluated by electron paramagnetic resonance (EPR) spectroscopy with CPH spin probes).

Elderly Patients With Type 2 Diabetes and Cognitive Exercises

The study was planned as a single-center, prospective randomized controlled study. Individuals over 65 years of age with type 2 diabetes without severe cognitive impairment will be included in the study. The primary aim of the study is to improve the cognitive functions of the patients after the interventions. The secondary aim is to strengthen patients' diabetes self-management and increase their quality of life, especially by improving their glycemic control. For these purposes, in our study, patients will be randomized into three groups: "cognitive exercise and diabetes education", "diabetes education only" and "control" group. The control group will be provided with standard outpatient diabetes education. Individuals who will be in the "cognitive exercise and video training" group will watch a total of 12 diabetes education videos prepared by the researcher, in which a different topic will be discussed every week for 3 months, and they will also participate cognitive exercises for 15-20 minutes a day for 3 months via a mobile application. Individuals in the "diabetes education only" group will similarly watch a total of 12 diabetes education videos prepared by the researchers. Patients will be evaluated in terms of cognitive function, psychosocial problems (anxiety, depression, stress), glycemic control (HbA1c), diabetes management and quality of life before the interventions, at 3 months and 6 months.

Glucose Monitoring After Acute Myocardial Infarct in People With Diabetes

Glucose monitoring after Acute Myocardial infarct in people with diabetes is a Dexcom funded study that is investigating whether the use of continuous glucose monitors (Dexcom ONE model) in people with type 2 diabetes facilitates time in glycaemic range in the 6 months after an acute myocardial infarction. As an exploratory outcome it will investigate whether time in glycaemic range is associated with changes in mortality and major adverse cardiac events in the 6 months after acute myocardial infarct.

Optimized Care of People With Diabetes and Foot Complication in Primary Care

The goal of this observational study is to create and evaluate and new management, by using eHealth tools, to prevent diabetic foot ulcers. The main questions it aims to answer are: 1. Validation a. Is a method for foot assessment, that uses eHealth tools, valid regarding its usefulness? b. Is a method for foot assessment, that uses eHealth tools, reliable regarding the generated risk stratification? 2. Mapping 1. How do health care professionals and patients with diabetes experience that the future foot examination should be designed? 2. What experiences have health care professionals and patients with diabetes to use an eHealth tool supporting the annual foot examination? 3. Interviews - to use a paper format supporting a structured foot assessment a. How do health care professionals experience to use a structured foot form, in paper form? 4. Interviews - footwear a. What factors that influence how patients with diabetes choose their footwear? 5. Interviews - usability test of using an eHealth tool a. How could a digital eHealth tool be designed? b. How could a digital eHealth solution be implemented, managed and spread in public health care setting? i. Participants will: 1\. fill in questionnaires 2. be interviewed 3. test eHealth solutions supporting the foot examination 6\. Experiences of using an eHealth tool supporting the foot assessment a. How could a digital eHealth tool be designed? 7\. Questionnaires regarding self-perceived quality of life, the experiences of the visit at the care unit, transportation to the care unit. a. Patients that visits care fills in a questionnaire regarding self-perceived quality of life (EQ-5D), a modified version of National Patient Survey, the diabetes questionnaire and a questionnaire regarding their travels and time for travels to and from the visit to the care unit. 8\. Critical evaluation of complexity 1. Exists complexity in the development, test, management, spread and sustain of an eHealth tool supporting foot examination and self-care of the feet in diabetes. 2. How could a digital eHealth solution be implemented, managed and spread in public health care setting? 9\. Long term effect a. What is the long-term effect of using an eHealth tools supporting a structured foot examination?

Pathogenesis of Kidney Disease in Type 1 Diabetes: a Modern Kidney Biopsy Cohort (The PANDA Study)

Diabetic kidney disease (DKD) occurs in up to 40% of people with type 1 diabetes (T1D), often leading to kidney failure and markedly magnifying risks of cardiovascular disease and premature death. Landmark T1D kidney biopsy studies identified the classic pathological lesions of DKD, which have been attributed largely to hyperglycemia. Recent advances in continuous glucose monitoring (CGM) and automated insulin delivery have facilitated improved glycemic control, but the residual risk of DKD continues to be high. In addition, obesity and insulin resistance (IR) have accompanied intensive glycemic therapy and may promote mitochondrial dysfunction and inflammation. Deciphering the molecular underpinnings of DKD in modern-day T1D and identifying modifiable risk factors could lead to more effective and targeted therapies to prevent DKD.

Optimized Diagnosis and Precision Medicine of MODY

The goal of this observation is to establish a complete registry for the clinical manifestations, environment, genetic, and other related gene variation information of young-onset diabetic patients. Moreover, according to the physiological and pathological mechanisms of different genes, the impact on the clinical characteristics of diabetes, the therapeutic response to drugs, and the impact on complications will be analyzed. The main questions are: 1. The distribution of different types of MODY 2. The phenotypes and clinical characteristics of different types of MODY 3. Response to antidiabetic drugs among different types of MODY Once the participant is enrolled, their questionnaire information (including disease course and development, health history, family history, drug history, etc.), medication, outpatient/inpatient medical history, etc. will be collected and logged in. Blood and urine samples will also be collected for biochemical tests genetic testing, etc. At the same time, the investigators will conduct a continuous follow-up on a regular basis (3 months, 6 months, 12 months, 24 months, and 5 years after the study subject is enrolled). Young-onset type 2 diabetes will be compared to see the difference in clinical presentations and responses to antidiabetic drugs.

Quantifying Artificial Pancreas-related Changes in Diabetic Neuropathy

A complication of diabetes mellitus is damage to nerves called neuropathy. There are several mechanisms involved that will lead to the development of neuropathy. Neuropathy can lead to foot ulcers, infections and amputations. Patients with neuropathy may also experience pain, which can be difficult to control and the medications are limited by side effects. Despite this there are no approved treatments to reverse the progression of neuropathy and the management of patients is focused on controlling blood glucose and other metabolic factors to prevent neuropathy and its symptoms from getting worse. Patients with type 1 diabetes are prescribed multiple daily injections (MDI) of insulin to manage their glucose control. However, insulin pump therapy and, more recently, automated insulin delivery (AID) or the Artificial Pancreas can be used as the insulin delivery method for patients with type 1 diabetes mellitus. Manchester Diabetes Centre is the first adult diabetes centre in Europe to pioneer and use a commercially-approved AID in clinical practice. Insulin pump therapy and AID have the advantage of being able to provide insulin at variable doses, which is closer to the natural process occurring within an individual without diabetes. Both are currently considered to be the most physiological method of insulin delivery and have been shown to improve glycaemic control, quality of life (QOL) and reduce the risk of hypoglycaemia (low blood glucose level). The investigators have previously shown in a small group of people that use of an insulin pump therapy may improve symptoms of painful neuropathy via a more stable glucose profile. The peaks and drops in insulin may make neuropathy worse. In this study the investigators aim to investigate the use of insulin pump therapy and AID in their effect on neuropathy. This will be in comparison to a control group of patients on MDI. The investigatorsbwill use a variety of neuropathy measures and symptom questionnaires to assess structural and functional neuropathy status. The investigators hypothesise that those patients receiving the newer technologies will demonstrate an improvement in symptoms and nerve regeneration. This finding would have a significant impact for patients as it would provide evidence to suggest that those patients with neuropathy should be put onto an insulin pump or AID to improve neuropathy and its symptoms. As these are treatments that are already available on the NHS to patients satisfying specific criteria this study aims to show benefit in this cohort of patients which can be implemented immediately in clinical practice.

Effectiveness of Focused Tele-education in Reducing Diabetes Complications During Ramadan

Introduction Diabetes is a global emergency with detrimental clinical and financial consequences. Poorly managed diabetes leads to a myriad of serious complications, especially cardiovascular and infectious complications, with consequent increased cost and mortality rate. For Muslims in particular, the annual fasting month of Ramadan is one such period when diabetes control is essential. Adequate adjustments in diabetes management need to be made in line with the allowed mealtimes to avoid the risk of diabetes complications during Ramadan. Objective Investigators aim to investigate the effectiveness of Ramadan-focused structured diabetes tele-education to reduce diabetes complications during Ramadan fasting for Muslims with diabetes in South East Asia. Methodology In a parallel group randomized controlled trial, investigators aim to recruit 300 adults with diabetes who are able to fast at least 15 days in Ramadan. You will be randomized to the intervention group comprising of a Ramadan-focused structured diabetes tele-education and control group receiving standard care. You will be reviewed again after Ramadan. The primary outcome is the incidence of hypoglycemia in Ramadan. The secondary outcomes are incidence of other diabetes complications in Ramadan episodes including hyperglycemia, episodes of acute infections, attendances in clinic and emergency department, hospital admissions, and compliance to recommendations for diabetes management during Ramadan. Clinical Significance The study enables investigators to evaluate Ramadan-focused structured diabetes tele-education to reduce the risk of diabetes complications for a large population during the fasting month.

Dynamic Parameters of Glucose Control in Relation to Biomarkers in Serum and Intraocular Fluid in Patients With Diabetes

Our project investigates the new characteristics of diabetic retinopathy using liquid eye biopsy in combination with novel parameters of glucose control obtained with continuous glucose monitoring. This approach will bring new knowledge and implications for future therapies.