Clinical Research Directory

Non-weight Bearing Exercise for Accelerated Healing of Diabetic Foot Ulcers

The goal of this study is to improve the therapeutic management of diabetic foot ulcers (DFU). The main questions to answer are if a program of non-weight bearing exercise helps the DFU heal faster than standard wound care. This randomized clinical trial will determine how blood flow to the ulcer and whole body metabolism may be improved with exercise. Participants will be randomized to either exercise + standard wound care or standard wound care alone and undergo testing for leg blood flow, fitness and measures of metabolism through blood draws. The intervention period is 6-weeks. Eligible participants must have an existing foot ulcer uncomplicated by infection and be medically cleared to exercise.

SGLT2 Inhibition in Addition to Lifestyle Intervention and Risk for Complications in Subtypes of Patients With Prediabetes

More than 50% of patients with type 2 diabetes develop micro- and/or macrovascular complications during the course of the disease. Additionally, many patients at risk for diabetes develop metabolically driven complications including kidney and heart disease. Thus, it is of utmost importance to improve prevention of T2D and with this complications. Remission of prediabetes, i.e. normalization of hyperglycemia by means of lifestyle intervention is one of the most effective ways to prevent the development of T2D and complications. Novel sub-phenotyping analysis identified clusters of risk for diabetes associated with different complications, opening opportunities to new therapeutic approaches, despite and in addition to lifestyle changes. So far, pharmacological therapy is not indicated for patients with prediabetes. Remission of hyperglycemia associated with prediabetes during lifestyle interventions not only prevents T2D but is also linked with reduced albuminuria and lower microvascular and kidney complications. Thus, reaching normoglycemia (i.e. prediabetes remission) is important for reducing the risk of (pre-)diabetes-associated complications including micro- and even macrovascular disease. In patients with T2D, recent data show that dapagliflozin can improve diabetes remission, and thus, likely complications. However, to date no data have assessed whether or not this is also true in patients with hyperglycemia related to prediabetes which, as outlined above, already causes different complications. Subphenotyping of patients with newly onset diabetes suggests that for some individuals, it would be too late to start interventions against dagainst complications at the time of diagnosis of type 2 diabetes. Therefore, individuals at elevated risk to develop T2D and complications should receive preventive measures well before the diagnosis of T2D. This study will provide evidence whether such an early intervention contributes to the remission of hyperglycemia related to prediabetes to protect from associated complications such as renal disease. The studied population will comprise individuals who have hyperglycemia in the range of prediabetes and are thus prone to not only develop T2D, but also early nephropathy but in clinical practice do not receive medical treatment due to the early stage of the disease. These subjects will receive Dapagliflozin 10 mg or Placebo for 6 months. The placebo treatment arm reflects current practice. In order guarantee a benefit the patients in the placebo arm will receive a lifestyle intervention.

Susceptibility to Infectious Diseases in Obesity

The role of intestinal microbiota is becoming ever more important in the context of obesity, type II diabetes (T2D), and infectious disorders as represented by the emerging discipline "therapeutic microbiology". The gut microbiota is strictly interconnected with obesity and T2D playing also an important role in immune system regulation. Obesity and diabetes can lead to chronic inflammation, which results in the secretion of pro-inflammatory cytokines like IL-6, IL-1, and TNF-alpha, causing immune system alteration which predisposes patients with obesity and T2D to chronic infections. Therefore, the principal aim of the study is to investigate changes in gut microbiota composition between patients with chronic infections or not, so as to attribute to specific phyla the formation of the infections in these patients.

Promoting Alternatives to Sulfonylureas to Improve Patient Safety in Type 2 Diabetes

Sulfonylurea medications are unsafe for older patients with diabetes. They are associated not only with hypoglycemia, but also with falls and increased cardiovascular risk. Yet they continue to be prescribed frequently. Indeed, older adults with type 2 diabetes, who are especially prone to adverse effects, are more likely to be prescribed sulfonylureas than younger patients. This is unfortunate since over the past several years, newer, safer, and more effective classes of medications (GLP-1 agonists and SGLT2-inhibitors) have emerged. The investigators acknowledge that sulfonylureas are inexpensive and that their low cost is a driver of continued use. However, the investigators believe patients and providers should have discussions about the risks of sulfonylureas and safer and more effective alternatives, to make diabetes care safer overall in ambulatory settings. Our research is designed to promote such discussions. The investigators will first identify patients taking sulfonylureas regularly. Next, using recommendations from AHRQ and the Canadian Deprescribing Network, the investigators will empower patients to discuss their medications with their providers through a simple question prompt sheet. Patients will be divided into an intervention group which receives explicit prompting questions, and a control group that receives a general brochure on diabetes medications. Health care providers will receive education about newer diabetes medications through case-based discussions and academic detailing. Finally the investigators will measure key outcomes including the proportion of patients who have discussions about sulfonylureas and alternatives, rates of discontinuation, and measures of control of diabetes and associated cardiovascular risks. The investigators will also evaluate the experiences of patients and providers qualitatively through brief, semi-structured interviews. Should our multi-faceted, patient-oriented intervention prove effective in promoting discussions of sulfonylureas and alternatives, and also discontinuation of sulfonylureas and switching to newer alternatives, the investigators will incorporate our prompting questions into routine care for patients taking sulfonylureas. Our intervention can be easily disseminated to other settings and therefore has considerable potential to improve safety among patients with type 2 diabetes nationwide.

The PIVOT Trial: Project on EHR-Integrated Lifestyle Interventions for Adults Aged Fifty and Older

This is a multisite clinical trial of healthy lifestyle programs for middle-to-older-aged adults (50 -74 years) to improve their weight and, therefore, reduce risk for chronic disease. This study will investigate whether a proven, self-directed video-based lifestyle program can be significantly enhanced with the assistance of a coach via videoconference or phone to help people as they adopt healthy eating and exercise behaviors. Additionally, the study will examine what factors might explain why some people achieve better outcomes than others. Understanding this can help to tailor the program to an individual for personalized care in the future. Importantly, this study aims to demonstrate how readily a digital lifestyle program, with or without remote coaching, can be seamlessly delivered to patients at home via the patient portal of their electronic health record. This practical use of existing telehealth tools could be a feasible and effective means to offer behavioral treatments during routine medical care.

Integration of a Trained Language Model to Improve Glycemic Control With the My Heart Counts Smartphone App

Type 2 diabetes (T2D) is one of the most common and fastest growing diseases, affecting 1 in 8 adults (nearly 800 million) worldwide by 2045. Sedentary behavior and increased adiposity are major risk factors for T2D. Cardiovascular disease is the leading cause of death in those with T2D, while diabetic microvascular disease, causing kidney disease, neuropathy, and retinopathy, contributes to T2D morbidity. Physical activity is one of the most potent therapies in preventing/treating T2D and its complications. Mean daily steps is a proxy for physical activity, with even modest improvements in step count (i.e., +500 steps) associated with decreased T2D and mortality. However, adherence to regular physical activity remains low in T2D patients, with short-term decreases in daily step count associated with impaired glycemic control and T2D recurrence. The investigators have developed an artificial intelligence (AI) language model (similar to ChatGPT), which can automatically generate coaching prompts to encourage physical activity by incorporating an individual's stage of change. The investigators will extend our research using the My Heart Counts (MHC) smartphone app to 1) validate the efficacy of the AI-generated prompts in patients with T2D and 2) perform a longer-term randomized crossover trial using the language model as a social accountability chatbot - encouraging participants to maintain their physical activity changes over months. The investigators hypothesize that my AI-assisted coaching prompts will significantly increase 1) mean daily step count by 500 steps in 1,000 adults recruited nationwide over a 7-day period, and 2) improve HbA1c and weight via long-term behavior change over a 24-week intervention period.

Continued Access to the Endogenex System for Participants in the ReCET Pivotal Study

This study is designed to collect real-world data on the safety and performance of the Endogenex System in the cohort of participants who were originally randomized to the sham control arm of the ReCET Study.

Safety and Effectiveness of Endoscopic Intestinal Re-Cellularization Therapy in Individuals With Type II Diabetes

This study is designed to evaluate the safety and effectiveness of endoscopic intestinal re-cellularization therapy in individuals with type 2 diabetes (T2D) inadequately controlled on non-insulin glucose-lowering medications.

Understanding and Addressing Risks of Low Socioeconomic Status and Diabetes for Heart Failure

This study aims to determine whether a 6-month multilevel intervention involving problem-solving training, exercise training and support from community health workers is more effective in improving outcomes for individuals with low socioeconomic status, type 2 diabetes, obesity, and early cardiac dysfunction than receiving education and access to a community exercise facility.

A Post-Marketing Safety Study of Dorzagliatin in Patients With Type 2 Diabetes

The primary objective of this study is to evaluate the long-term safety of Dorzagliatin in a larger population of type 2 diabetes mellitus patients by collecting the post-marketing clinical safety data of Dorzagliatin.

Real Time Continuous Glucose Monitoring System in T2DM With Pregnacy

The prevalence of type 2 diabetes mellitus (T2DM) in women of childbearing age is increasing rapidly, and low glucose compliance leads to an increased risk of adverse pregnancy outcomes for mothers and infants during pregnancy in women with T2DM. Real-time continuous glucose monitoring (CGM) is an important tool for glucose monitoring and patient education, as it can continuously record blood glucose throughout the day and provide real-time feedback on high and low blood glucose levels. This is a multicenter, open-label, randomized controlled clinical study to investigate the efficacy, safety, and maternal and infant pregnancy outcomes of using real-time CGM monitoring compared with conventional self-monitoring of blood glucose (SMBG) on the basis of multidisciplinary management in pregnant women with T2DM. One hundred and twenty pregnant women with T2DM in early pregnancy who were enrolled in intensive insulin therapy were randomly divided into the real-time CGM group and the conventional SMBG group. The real-time CGM intervention group wore real-time CGM for more than 50% of the pregnancy in addition to regular SMBG; the control group only performed regular SMBG. Both groups wore Medtronic iPro 2 for 3 days in early, mid and late pregnancy, and the time in the target range of blood glucose (TIR) was recorded in a blinded manner. Primary outcome: differences in TIR between the two groups of pregnant women in early, mid, and late pregnancy. Secondary outcomes included differences in glycated hemoglobin, hypoglycemia, insulin dose before delivery, pregnancy weight gain, and maternal and infant pregnancy outcomes.

Successfully Achieving and Maintaining Euglycemia During Pregnancy for Type 2 Diabetes Through Technology and Coaching

The ACHIEVE RCT will measure the effect of the intervention (mHealth app with CGM, provider dashboard, and care team coaching) compared to current standard care (prenatal visits, self-monitored blood glucose, and certified diabetes care and education specialist) on achieving glycemic control (hemoglobin A1c \<6.5% in the third trimester). We hypothesize a 25% absolute increase in the proportion of participants in the intervention group who will meet the target hemoglobin A1c \<6.5% in the third trimester compared to the standard care group

The Impact of Geriatric Assessment on the Treatment Plan of Elderly Patients With T2DM

Introduction: With the aging of the world population and the increasing incidence of type 2 diabetes mellitus (T2DM) with age, the number of elderly individuals living with diabetes has been considerably rising. It is known that uncontrolled T2DM negatively impacts various health outcomes, including geriatric outcomes such as sarcopenia, frailty, immobility, incontinence, and infections. Current medical literature fails to establish appropriate glycemic targets for different elderly profiles. Although guidelines emphasize the need to individualize targets, there is no concise tool to identify which individuals benefit from each therapeutic approach. Data suggest that frailty is the best predictor of negative outcomes in elderly patients living with T2DM. The Clinical Frailty Scale (CFS) and the 10-minute Targeted Geriatric Assessment (TaGA-10) are validated tools for prognosis in elderly patients and for identifying frail elderly individuals. Methods: Randomized controlled trial. Elderly individuals diagnosed with T2DM at a tertiary care outpatient clinic will be included. All enrolled patients will undergo geriatric assessment using CFS, TaGA-10, and Charlson Comorbidity Index. Patients will be randomized into usual care and intervention groups, and the intervention involves providing the geriatric assessment to the care team to support their decisions. The adequacy of the therapeutic approach will be measured in one week by reviewing the consult record or interviewing the physician. The clinical impact on the frequency of hypoglycemia, falls, infections, hospitalizations, and mortality will be evaluated at 3 and 6 months by telephone interviews. Discussion: Current guidelines recommend using age, comorbidities, cognitive, and functional status to individualize therapeutic targets in elderly patients with T2DM; however, it is possible that these variables alone may not be sufficient to classify all elderly individuals in their complexity adequately. A tool with such power and easy to use in clinical practice is necessary.

The Effects of Glucagon on Hepatic Metabolism in People With Type 2 Diabetes After Caloric Restriction

Caloric restriction (and RYGB) improves insulin action and lowers fasting glucose, glucagon and EGP, without changes in postprandial EGP and glucagon concentrations. Caloric restriction also improves hepatic steatosis and lowers fasting AA. These changes may represent restoration of glucagon's hepatic actions. This experiment will determine whether caloric restriction improves glucagon's actions on hepatic amino acid, carbohydrate and lipid metabolism in T2DM in comparison to a baseline experiment performed separately in people with T2DM.

Feasibility and Adherence to a Technology-assisted Home-based Strength Training Program in Adults With Type 2 Diabetes Mellitus and Mild Cognitive Impairment

This is a single-arm feasibility study employing a pre-post design with a 12-week intervention period. The study utilizes a telehealth-assisted home-based resistance exercise program, with a structured progression from supervised to unsupervised sessions over 12 weeks.

The Bennett Kids PowerUP Project

The study proposes a randomized pilot and feasibility study of a lifestyle modification program to promote healthy diet and activity in rural-dwelling children to reduce Type 2 Diabetes risks. Intervention participants will receive 6 months of programming to include: * 16 activity packs; * 9 health coach sessions; * unlimited access to a resource toolbox. Control participants will receive 6 activity packs promoting science, technology, engineering, and math (STEM) learning and 6 check-in calls to support retention.

The Effects of Glucagon on Hepatic Metabolism

Whether impaired postprandial glucagon suppression in prediabetes and T2DM is an attempt to overcome resistance to glucagon's actions on hepatic AA catabolism, a defect in α-cell function, or a combination of both are important, unanswered questions. NAFLD is associated with T2DM risk and impaired insulin action. Unfortunately, it is unclear if glucagon resistance is caused by obesity, hepatic steatosis or both. The experiments outlined will determine if glucagon's actions on hepatic amino acid catabolism and EGP interact with hepatic lipid metabolism in lean and obese subjects with and without T2DM (and with varying degrees of hepatic steatosis).

NAD Augmentation in Diabetes Kidney Disease

A phase 2a trial randomized, double-blind, placebo-controlled, parallel group trial to determine whether NMN administration improves DKD, as indicated by a significantly greater reduction in UACR compared with placebo administration. Eligible participants will be randomized to receive either 1000 mg NMN or placebo twice daily.

The CARING Study: Creating and Restoring Health Through Nutrition Guidance

The CARING study assesses the health benefits of nutrition education for Blue Cross Blue Shield subscribers, as well as potential healthcare cost savings to subscribers and the insurance company.

Type 2 Diabetes and Blood Brain Barrier Improvement

The majority of T2DM adults show thiamine (vitamin B1) deficiency which may contribute to impaired function. This study will examine patients with T2DM through brain MRI scans, cognition assessments, blood tests, and questionnaires. Our goal is to see if a thiamine treatment (taking vitamin B1 capsules) can improve function. Patients will be asked to come to UCLA two times three months apart and each visit will last about 2.5-3 hours.

Mitochondrial Substrate Utilization in the Diabetic Human Heart

Diabetes can lead to heart failure independently, but the underlying causes remain incompletely understood. The main aim of this study is to identify differential regulation of mitochondrial substrate utilization and complex activity in heart failure and type 2 diabetes mellitus (T2DM). For this, we will conduct a prospective, observational study to examine myocardial mitochondrial oxidative function and related metabolic parameters, gene expression, histological markers, and inflammation in cardiac tissue from patients with heart failure or patients after heart transplantation. We will further assess cardiac function using cardiac magnetic resonance imaging with and without stress protocols and magnetic resonance spectroscopy. Glycemic control/T2DM will be characterized by oral glucose tolerance tests. The results of this project will help to better understand the cellular mechanisms of the development of diabetic cardiomyopathy and contribute to the development of early diagnostic, as well as therapeutic approaches for the prevention and treatment of diabetic cardiomyopathy.

Comorbidities Resolution After MGB Surgery and Change in Body Composition

This observational study aims to learn about the correlation between the improving comorbidities associated with obesity after MGB (Mini-Gastric Bypass) surgery and changes in body composition in morbidly obese patients. The main questions it aims to answer are: To study the correlation between the improving comorbidities associated with obesity after MGB(Mini-Gastric Bypass) surgery and changes in body composition. Other objectives are: * Changes in the parameters of the metabolic syndrome after surgery * Changes in the cardiovascular risk biomarkers after metabolic surgery * Emergence in complications arising out of surgery requiring any intervention or causing a prolonged hospital stay, or requiring additional outpatient visits. Type of Study: An observational study in which participants with morbid obesity will undergo mini-gastric bypass surgery as per routine protocol. No separate experimental interventions will be done in the study for the participants.

Ketones, SGLT2, HFrEF

The study team will examine the effects of elevated plasma ketone levels following initiation of SGLT2 inhibitor therapy in high-risk type 2 diabetes mellitus (T2DM) individuals with heart failure (HF) with reduced ejection fraction (HFrEF) providing an energy-rich fuel that is taken up with great avidity by the myocardium, to measure change in Left Ventricle diastolic and systolic function

The Effect of rs7903146 Genotype on Islet GLP-1 Production in Humans

The investigators recently demonstrated that blockade of Glucagon-Like Peptide-1's (GLP-1) receptor (GLP1R) results in changes in islet function without changes in circulating GLP-1. These effects are more pronounced in people with early type 2 diabetes (T2DM) in keeping with increased expression of PC-1/3 and GLP-1 that is observed in diabetic islets. However, its regulation is at present unknown. Common genetic variation in the TCF7L2 locus (T-allele at rs7903146) arguably confers the greatest genetic risk of T2DM. It is associated with α- and β-cell dysfunction. TCF7L2 (the product of TCF7L2) was first described as the transcription factor necessary for proglucagon expression in intestinal L-cells (which secrete GLP-1). This led to speculation that TCF7L2 confers risk of diabetes via changes in circulating GLP-1. This has turned out to not be the case. This raises the possibility that these diabetogenic effects are mediated via an inability of islet GLP-1 to adapt to rising glycemia. Therefore, this experiment will determine the contribution of islet GLP-1 to the functional abnormalities of the islet associated with the TCF7L2 locus.