24 Clinical Trials for Various Conditions
Powerful new drugs that can prevent or delay end stage kidney disease (ESKD) - so called sodium-glucose cotransporter-2 inhibitors (SGLT2i) - are now available for patients with type 2 diabetes. Whether these drugs have similar effects in patients with type 1 diabetes (T1D) remains unknown because of the few studies in this population, due to concerns about the increase in risk of diabetic ketoacidosis (DKA, a serious, potentially fatal acute complication of diabetes due to the accumulation of substances called ketone bodies) observed with SGLT2i therapy in T1D. One of the few T1D studies conducted to date showed that implementing an enhanced DKA prevention plan can reduce the risk of DKA associated with the SGLT2i sotagliflozin (SOTA) to very low levels. In the present study, a similar DKA prevention program will be used to carry-out a 3-year trial to test the kidney benefit of SOTA in 150 persons with T1D and moderate to advanced DKD. After a 2-month period, during which diabetes care will be standardized and education on monitoring and minimizing DKA implemented, eligible study subjects will be randomly assigned (50/50) to take one tablet of SOTA (200 mg) or a similarly looking inactive tablet (placebo) every day for 3 years followed by 2-months without treatment. Neither the participants nor the study staff will know whether a person was assigned to taking SOTA or the inactive tablet. Kidney function at the end of the study will be compared between the two treatment groups to see whether SOTA prevented kidney function loss in those treated with this drug as compared to those who took the inactive tablet. The DKA prevention program will include participant education, close follow-up with study staff, continuous glucose monitoring, and systematic ketone body self-monitoring with a meter provided by the study. If successful, this study will provide efficacy and safety data that could be used to seek FDA approval of SOTA for the prevention of kidney function decline in patients with T1D and DKD.
The aim of this study is to test the hypothesis that sotagliflozin (SGLT1/2 inhibitor) and ambrisentan (ERA) combination therapy augments nephroprotection and mitigates fluid retention and ketogenesis in people with T1D through complementary and synergistic mechanisms of actions.
The purpose of this study is to evaluate the safety and tolerability of two dosing regimens of FG-3019 administered over 12 weeks in patients with diabetic nephropathy and proteinuria on background angiotensin converting enzyme inhibitor (ACEi) and/or angiotensin II receptor antagonist (ARB) therapy.
In type 1 diabetes (T1DM), automated insulin delivery (AID) systems such as the hybrid closed loop artificial pancreas (HCL AP) combine the use of an insulin pump, continuous blood sugar monitor, and control algorithm to adjust background insulin delivery to improve time in target blood sugar range. Systems such as the predictive low glucose suspend system (PLGS) pause insulin delivery to try and reduce low blood sugars. We aim to complete a pilot study involving recruitment of youth ages 7 to 18 years from the following groups with type 1 diabetes: control participants consisting of youth on either multiple daily insulin injections or conventional insulin pump therapy that plan to continue with their current treatment modality, youth being transitioned to the HCL AP system, and youth being transitioned to the PLGS system. Individuals will be recruited into each of the aforementioned study groups based on their own expressed desire to either continue on MDI/standard insulin pump therapy or transition to either the HCL AP or PLGS systems. The decision to either continue with current therapy or transition therapy will remain entirely up to the participant and their family and will be based on personal preference and insurance coverage for that individual. We will not be randomizing the participants to any given treatment group during this study but rather will be recruiting based on the participant's decision. We would like to complete a physical exam with pubertal staging, collect blood and urine samples to evaluate cardiometabolic and renal markers, and complete a DXA scan to evaluate total lean and fat mass. After 3-6 months of either continuation of current treatment with either multiple daily insulin injections or conventional insulin pump therapy or transitioning to the HCL AP or PLGS systems, we would like to repeat the previously described blood, urine, and imaging tests for comparison. We are interested in examining the impact of the HCL AP and PLGS systems on maintaining blood sugars in target range, insulin sensitivity, and markers of cardiometabolic and renal function. We hypothesize that pauses in insulin delivery, as seen in the setting of automated insulin delivery systems, will result in improvements in insulin sensitivity, cardiometabolic markers, and renal function markers.
The Researchers will assess the safety, tolerability, dosing effect, and early signals of efficacy of intra-arterially delivered autologous (from self) adipose (fat) tissue-derived mesenchymal stem/stromal cells (MSC) in patients with progressive diabetic kidney disease (DKD).
Over 1.25 million Americans have type 1 diabetes (T1D), increasing risk for early death from cardiorenal disease. The strongest risk factor for cardiovascular disease (CVD) and mortality in T1D is diabetic kidney disease (DKD). Current treatments, such as control of hyperglycemia and hypertension, are beneficial, but only partially protect against DKD. Hyperfiltration is common in youth with T1D, and predicts progressive DKD. Hyperfiltration is also associated with early changes in intrarenal hemodynamic function, including increased renal plasma flow (RPF) and glomerular pressure. Intrarenal hemodynamic function is strongly influenced by the renin-angiotensin-aldosterone system (RAAS), which is also considered a key player in the pathogenesis of DKD. Preliminary data demonstrate differences in intrarenal hemodynamic function and RAAS activation in early and advanced DKD in T1D. However, the pathophysiology contributing to the differences observed in RAAS activation and intrarenal hemodynamic function in T1D are poorly defined Animal research demonstrates that arginine vasopressin (AVP) acts directly to modify intrarenal hemodynamic function, but also indirectly by activating RAAS. Preliminary data suggest that elevated copeptin, a marker of AVP, which predicts DKD in T1D adults, independently of other risk factors. However, no human studies to date have examined how copeptin relates to intrarenal hemodynamic function in early DKD in T1D. A better understanding of this relationship is critical to inform development of new therapies targeting the AVP system in T1D. Accordingly, in this study, the investigators propose to define the relationship between copeptin and intrarenal hemodynamics in early stages of DKD, by studying copeptin levels, renal plasma flow, and glomerular filtration in youth (n=50) aged 12-21 y with T1D duration \< 10 y.
Despite improvements during the past 20 years in blood glucose and blood pressure control, diabetic kidney disease remains one of the most important causes of health problems in patients with diabetes. Novel treatments to complement blood glucose and blood pressure control are urgently needed. The goal of this study is to see whether a medication called allopurinol may help prevent loss of kidney function among people with type 1 diabetes. Allopurinol has been used for many years to decrease high blood uric acid and treat gout - a disease characterized by arthritis, especially of the foot joints. There is evidence suggesting that allopurinol might also be useful in people with diabetes who have normal or moderately impaired kidney function to decrease the risk of developing advanced kidney disease in the future. To prove this beneficial effect of allopurinol, we will be conducting an international clinical trial at eight diabetes centers, enrolling approximately 480 patients with type 1 diabetes who are at increased risk of developing kidney disease. Participants will be randomly assigned to take allopurinol or placebo (inactive pill) for three years, during which they will be followed through periodical visits. To prevent any possible bias, neither the participants nor the clinical staff knows who is taking allopurinol and who is taking the placebo. Kidney function will be measured at the beginning and at the end of the treatment period to see whether patients taking allopurinol experience a slower loss of kidney function over time as compared to those taking the inactive pill. If this trial is successful, the reduction in health problems resulting from the prevention or delay of kidney function loss due to the use of allopurinol would have a major impact on the lives of type 1 diabetic patients as well as on society at large, significantly reducing the human and financial costs associated with diabetic kidney disease. Because of the emphasis on early intervention, the proposed trial, if successful, will establish a new paradigm in treatments to slow or prevent progression towards end stage kidney disease in type 1 diabetes far beyond anything achieved to date.
Matrix metalloproteinases (MMPs) are a family of protein-degrading enzymes that are involved in the breakdown and remodeling of many tissues and organs. Abnormal activity of these enzymes has been implicated in many disease processes including rheumatoid arthritis, dental disease and metastatic cancer. Recent studies also suggest that elevations in blood sugar may abnormally effect MMP enzyme activity. Decreased activity of some of these MMP enzymes may be a partial cause of the abnormal enlargement of the kidney (renal hypertrophy) seen at the start of diabetic kidney disease (nephropathy). Preliminary clinical data from our laboratory confirm that children with newly diagnosed type 1 diabetes mellitus (DM) have lower blood levels of some of these enzymes at the time of very high blood sugar readings. However, these enzyme levels become normal again as blood sugar levels improve with insulin treatment. In the present study, we propose to investigate the hypothesis that MMPs are involved in the cause of diabetic kidney disease by measuring concentrations of specific MMPs and some related proteins in the blood and urine of patients with type 1 DM who are between the ages of 14-40 years. We will enroll some patients who are recently diagnosed with diabetes, some who have had diabetes for several years, but without signs of kidney disease, and some with long-term diabetes and various degrees of kidney disease. Continuous Subcutaneous Glucose Monitoring, conducted for 3-4 days, will also be provided as a part of this study, to determine how different levels of blood sugar control might relate to different levels of MMP enzyme activity in the blood. We anticipate that this study will help to establish a link between abnormal MMP activity and the cause of nephropathy in type 1 DM, allowing scientists to design better therapies for the prevention and treatment of diabetes-related kidney problems.
The study is designed to assess the efficacy, safety, tolerability, and transformation within the human body of INV-202 investigational drug in the treatment of adult participants with a diagnosis of Diabetic Kidney Disease due to either Type 1 diabetes mellitus or Type 2 diabetes mellitus.
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.
Diabetic kidney disease remains the leading cause of end-stage kidney disease (ESKD), rising in frequency in parallel with the epidemic of diabetes worldwide. The estimated lifetime risk of kidney disease in persons with type 1 diabetes (T1D) has been reported to be as high as 50-70%, although risk may be lower in excellent care environments. Two previous studies have suggested that a generic drug used to lower fats in blood (fenofibrate) may protect the kidney from damage due to diabetes. These data, however, were obtained among people with type 2 diabetes with clinical characteristics optimized for cardiovascular studies. Thus, a clinical trial specifically designed to evaluate the effects on the kidney is required to firmly show that this drug can prevent kidney damage in T1D. The goals of the present pilot study are to demonstrate the feasibility of such trial, gather essential information for designing and planning this study, and generate preliminary data. To this end, 40 participants with T1D and early-to-moderate diabetic kidney disease (DKD), at high risk of ESKD, will be enrolled at two clinical sites and assigned in a 1:1 ratio to treatment with fenofibrate or placebo for 18 months. Kidney function will be measured at the beginning and at the end of the study to evaluate the effect of fenofibrate.
The purpose of this study is to determine whether alkalinization of urine uric acid by 2 doses of sodium bicarbonate (1950mg) over 24-hours reduces precipitation and crystallization of urine uric acid over in adults with type 1 diabetes.
The purpose of this study is to determine if LY2382770 is safe and effective at protecting kidney function in participants with kidney disease due to diabetes.
Current medical therapies are not able to prevent progression of established macroproteinuira (i.e. diabetic nephropathy) to end-stage renal failure in type 1 (insulin dependent) diabetic patients. In this setting, proteinuria is a major risk factor for mortality. Pancreas transplantation, on the contrary, can revert diabetic nephropathy and thereby prevent end-stage chronic renal failure, with theoretically lower risk of death as compared to current medical therapies.The main objective of this study is to assess superiority of isolated pancreas transplantation versus intensive exogenous insulin therapy in type 1 diabetic patients with overt diabetic nephropathy and mildly reduced renal function. The primary endpoint is a composite efficacy/failure end-point including: patient mortality and renal function impairment during 5 years in patients with badly controlled diabetes and nephropathy resisting to up-to-date nephroprotective therapies.Main secondary objectives are safety and efficacy of both regimens, including proteinuria and renal histology evaluation, metabolic control and quality of life, acute and chronic extrarenal complications of diabetes, pancreas survival and all risks related to the transplant procedure (anaesthesia, surgery and immunosuppression side-effects) and to the intensive insulin therapy management.
Diabetic nephropathy is a frequent cause of end-stage renal disease. Reduction of dietary protein has been used to slow down renal disease progression, but patients are often unwilling to make these dietary changes. Other research suggests that changing the quality of dietary protein may be as effective as reducing the total amount of ingested protein. This study hopes to show that soy protein, a plant protein relatively high in essential amino acids and with high nutritional value, maye be beneficial to Type I diabetic patients with incipient renal disease.
The primary objective of this study is to determine the effects of semaglutide on kidney oxygenation and function in type 1 diabetes. The secondary objective is to determine the glycemic effects and safety of semaglutide in type 1 diabetes.
Diabetic kidney disease and cardiovascular disease remain the leading causes of morbidity and mortality in people with type 1 diabetes and are exacerbated with longer duration of diabetes and time outside goal glycemic range. Yet, type 1 diabetes is a complex disease with pathophysiology that extends beyond beta-cell injury and insulin deficiency to include insulin resistance and renal vascular resistance, factors that accelerate cardiovascular disease risk. We have shown that metformin improved peripheral insulin sensitivity and vascular stiffness in youth with type 1 diabetes on multiple daily insulin injections or standard insulin pumps. However, metformin's effect on kidney and endothelial outcomes, and the effects of type 1 diabetes technologies, with or without metformin, on any cardiovascular or kidney outcome, remains unknown. Automated insulin delivery systems combine an insulin pump, continuous glucose monitor, and control algorithm to modulate background insulin delivery and decrease peripheral insulin exposure while improving time in target range and reducing hypoglycemia. We hypothesize that automated insulin delivery systems, particularly when combined with metformin, may modulate renal vascular resistance and insulin sensitivity, thereby impacting cardiometabolic function. MANATEE-T1D is a randomized, double-blind, placebo-controlled trial of 4 months of metformin 2,000 mg daily in 40 youth aged 12-25 years with type 1 diabetes on automated insulin delivery systems vs. 20 control youth with type 1 diabetes on multiple daily injections plus a continuous glucose monitor or an insulin pump in manual mode plus a continuous glucose monitor which will assess for changes in calculated renal vascular resistance and gold standard measures of whole-body and adipose insulin sensitivity, arterial stiffness, and endothelial function.
This investigation is a randomized, double-blinded, placebo-controlled clinical trial in adult diabetic Pima Indians with normal urinary albumin excretion (albumin-to-creatinine ration less than 30 mg/g) or microalbuminuria (albumin-to-creatinine ration = 30-299 mg/g) to test the hypothesis that blockade of the renin-angiotensin system with the angiotensin receptor blocker (ARB) losartan can prevent or further attenuate the development and progression of early diabetic nephropathy in subjects with type 2 diabetes mellitus who are receiving standard diabetes care. One hundred seventy subjects were recruited for the study, all of whom had type 2 diabetes for at least 5 years, serum creatinine concentrations less than 1.4 mg/dl, and no evidence of non-diabetic renal diseases. Ninety-two of the subjects had normal urinary albumin excretion at baseline and other 78 had microalbuminuria. Subjects in each albumin excretion group were randomized to treatment with either the angiotensin II receptor antagonist, losartan, or placebo. Measurements of glomerular filtration rate (GFR), renal plasma flow (RPF) and fractional clearances of albumin and IgG will be made initially, at one month, and at 12-month intervals from baseline thereafter. A kidney biopsy was performed after six years in 111 subjects. Morphometric analysis of renal biopsies was used to determine differences in glomerular structure between treatment groups.
Type 1 diabetes (T1D) is a complex metabolic disorder with many pathophysiological disturbances including insulin resistance (IR) and mitochondrial dysfunction which are causally related to the development of diabetic kidney disease (DKD) and which contribute to reduced life expectancy. Renal hypoxia, stemming from a potential metabolic mismatch between increased renal energy expenditure and impaired substrate utilization, is increasingly proposed as a unifying early pathway in the development of DKD. By examining the interplay between factors responsible for increased renal adenosine triphosphate (ATP) consumption and decreased ATP generation in young adults with and without T1D, this study hopes to identify novel therapeutic targets to impede the development of DKD in future trials. The investigators propose to address the specific aims in a cross-sectional study with 30 adults with T1D and 20 controls without a diagnosis of diabetes. For this protocol, participants will complete a one day study visit at Children's Hospital Colorado. Patients will undergo a Dual-energy X-Ray Absorptiometry (DXA) scan to assess body composition, renal Magnetic Resonance Imaging (MRI) to quantify renal oxygenation and perfusion, and a Positron Emission Tomography/Computed Tomography (PET/CT) scan to quantify renal O2 consumption. After the PET and MRI, participants will undergo a hyperinsulinemic-euglycemic clamp to quantify insulin sensitivity. Glomerular Filtration Rate (GFR) and Effective Renal Plasma Flow (ERPF) will be measured by iohexol and PAH clearances during the hyperinsulinemic-euglycemic clamp. To further investigate the mechanisms of renal damage in T1D, two optional procedures are included in the study: 1) kidney biopsy procedure and 2) induction of induced pluripotent stem cells (iPSCs) to assess morphometrics and genetic expression of renal tissue.
The purpose of this study is to assess the safety and tolerability of allogeneic mesenchymal stem / stromal cell therapy in individuals with chronic kidney disease.
Over 1.25 million Americans have Type 1 Diabetes (T1D), increasing risk for early death from cardiovascular disease (CVD). Despite advances in glycemic and blood pressure control, a child diagnosed with T1D is expected to live up to 17 years less than non-diabetic peers. The strongest risk factor for CVD and mortality in T1D is diabetic kidney disease (DKD). Current treatments, such as control of hyperglycemia and hypertension, are beneficial, but only partially protect against DKD. This limited progress may relate to a narrow focus on clinical manifestations of disease, rather than on the initial metabolic derangements underlying the initiation of DKD. Renal hypoxia, stemming from a potential metabolic mismatch between increased renal energy expenditure and impaired substrate utilization, is increasingly proposed as a unifying early pathway in the development of DKD. T1D is impacted by several mechanisms which increase renal adenosine triphosphate (ATP) consumption and decrease ATP generation. Caffeine, a methylxanthine, is known to alter kidney function by several mechanisms including natriuresis, hemodynamics and renin-angiotensin-aldosterone system. In contrast, to other natriuretic agents, caffeine is thought to fully inhibit the local tubuloglomerular feedback (TGF) response to increased distal sodium delivery. This observation has broad-ranging implications as caffeine can reduce renal oxygen (O2) consumption without impairing effective renal plasma flow (ERPF) and glomerular filtration rate (GFR). There are also data suggesting that chemicals in coffee besides caffeine may provide important cardio-renal protection. Yet, there are no data examining the impact of coffee-induced natriuresis on intrarenal hemodynamic function and renal energetics in youth-onset T1D. Our overarching hypothesis in the proposed pilot and feasibility trial is that coffee drinking improves renal oxygenation by reducing renal O2 consumption without impairing GFR and ERPF. To address these hypotheses, we will measure GFR, ERPF, renal perfusion and oxygenation in response to 7 days of cold brew coffee (one Starbucks® Cold brew 325ml bottle daily \[205mg caffeine\]) in an open-label pilot and feasibility trial in 10 adolescents with T1D already enrolled in the CASPER Study (PI: Bjornstad).
Study Hypothesis: Reduction in albuminuria has been shown to decrease progression of diabetic nephropathy. In diabetic nephropathy patients treated with maximal antihypertensive doses with dual RAAS blockade (total daily dose valsartan 320 mg and either enalapril 40 mg or benazepril 40 mg daily, or losartan 100mg), persistent albuminuria reflects further additional RAAS activation. Microvascular renal disease due to increased RAAS activation may be more effectively treated with triple blockade by the addition of a direct renin inhibitor (DRI) Aliskiren.
This Stage II randomized, controlled, longitudinal trial seeks to assess the acceptability, feasibility, and effects of a driving decision aid use among geriatric patients and providers. This multi-site trial will (1) test the driving decision aid (DDA) in improving decision making and quality (knowledge, decision conflict, values concordance and behavior intent); and (2) determine its effects on specific subpopulations of older drivers (stratified for cognitive function, decisional capacity, and attitudinally readiness for a mobility transition). The overarching hypotheses are that the DDA will help older adults make high-quality decisions, which will mitigate the negative psychosocial impacts of driving reduction, and that optimal DDA use will target certain populations and settings.
This randomized study evaluates the effect of subcutaneous semaglutide /in combination with lifestyle counseling in patients with type 2 diabetes mellitus (T2DM), overweight/obesity, and stage 4-5 chronic kidney disease (CKD) or dialysis-dependent end-stage kidney disease (ESKD) on patients' eligibility for kidney transplantation at the end of 9 months.