Device-Less Islet Transplantation for Type 1 Diabetes
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: University of Alberta
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial tests a new method of transplanting insulin-producing cells under the skin for people with type 1 diabetes who struggle with standard treatments. The technique uses a small tube to create a supportive environment for the cells. This approach aims to improve blood sugar control by helping the transplanted cells survive and function effectively. This method is being explored as an alternative to insulin therapy, especially for those with severe blood sugar issues.
Do I need to stop my current medications for this trial?
The trial protocol does not specify if you need to stop taking your current medications. However, if you have a psychiatric disorder that is unstable or uncontrolled on current medication, you may not be eligible to participate.
What data supports the idea that Device-Less Islet Transplantation for Type 1 Diabetes is an effective treatment?
The available research shows that Device-Less Islet Transplantation can effectively manage Type 1 Diabetes. In a study with mice, this method reversed diabetes in 91% of the subjects and maintained normal blood sugar levels for over 100 days. This approach was successful even in mice with pre-existing diabetes and those with a strong immune response. Compared to other methods, this treatment does not require a permanent device, making it a promising option for diabetes management.
12345What safety data exists for device-less islet transplantation for Type 1 Diabetes?
The provided research does not contain safety data for device-less islet transplantation or related procedures like nylon catheter implantation or angiocatheter implantation. The studies focus on the use of drug-eluting stents in diabetic patients, which is unrelated to the treatment in question.
678910Is the treatment 'Implantation of Nylon catheter (Device-less sentinel unit)' a promising treatment for type 1 diabetes?
Yes, the treatment is promising. It involves a new way to transplant cells that make insulin, which can help people with type 1 diabetes. This method doesn't need a permanent device and has shown success in reversing diabetes in animal studies. It offers a simpler and safer option for managing diabetes.
234511Eligibility Criteria
This trial is for adults with Type 1 Diabetes who have unstable blood sugar levels, frequent hospital visits due to diabetic ketoacidosis, or reduced awareness of hypoglycemia. They must understand the study and consent to participate. Excluded are those under 18 or over 68, with certain medical conditions like severe heart disease, kidney issues, psychiatric disorders, high insulin requirements, pregnancy intentions without contraception use, substance abuse history including smoking within the last six months.Participant Groups
The trial tests a 'device-less' technique for transplanting insulin-producing cells under the skin in patients with Type 1 Diabetes. This method uses a temporary nylon catheter to create a favorable environment for cell survival by promoting new blood vessel growth without triggering adverse body reactions.
1Treatment groups
Experimental Treatment
Group I: Treatment GroupExperimental Treatment1 Intervention
Implantation of the Device-Less sentinel units. Ultrasound Monitoring. Islet Transplantation. Explantation of Device-Less Sentinels. Standard of Care. Concomitant Care. Post Transplant Testing and Visits. Participant Retention (nine month follow up assessment).
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
University of Alberta Clinical Islet Transplant ProgramEdmonton, Canada
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Who is running the clinical trial?
University of AlbertaLead Sponsor
Juvenile Diabetes Research FoundationCollaborator
References
[Islet transplantation in type I diabetes mellitus]. [2015]Type 1 diabetes mellitus results from autoimmune destruction of the insulin-secreting cells in the pancreas. The dramatic breakthrough in 2000 with the "Edmonton protocol" for successful solitary islet transplantation has restored optimism for the application of islet transplantation as a treatment for type I diabetes. Due to the recent successes, islet transplantation has evolved from a theoretical concept to its current status as a therapeutic option for patients with type 1 diabetes. Islet transplantation has shown to normalize metabolic control in a way that has been virtually impossible to achieve with exogenous insulin. The less invasive procedure of islet transplantation as compared to whole pancreas transplantation in patients with type 1 diabetes mellitus would be expected to be safer and much less costly. However, this procedure also requires lifetime immunosuppression with drugs. The limited availability of donor organs and the necessity of transplantation of several pancreata in order to achieve insulin independence limit this procedure to a small minority of patients. Unlike the North American centers, the European centers concentrated their efforts on islet after kidney and simultaneous islet kidney transplantation. The two Swiss islet transplantation programs have been pioneers in applying the steroid-free "Edmonton protocol" to simultaneous islet-kidney and islet after kidney transplantation. The long term follow-up showed that islet function decreases over time. In order to maintain insulin independence repeated islet transplants would have to be given to the patients. Therefore, there has been a change in paradigm over time. The major goal of islet transplantation focuses now on achieving a good blood glucose control and avoidance of severe hypoglycaemic episodes rather than only insulin-independence. Thus, due to the limited supply of donor organs, more patients can benefit from islet transplantation. Small insulin doses of exogenous insulin prevent stress on the islet in particular after meals and might help to maintain the transplanted islet mass over time. Due to the severe limitations of immunosuppression solitary islet transplantation is limited to a very small number of patients with type 1 diabetes. The most common indication for islet transplantation in Switzerland is terminal kidney failure in patients with type I diabetes. A simultaneous islet-kidney or pancreas-kidney transplantation should be offered to these patients. The choice between islet or pancreas transplantation is a matter of age and diabetic complications because the perioperative risk is considerably higher in pancreas transplantation.
Transplantation sites for human and murine islets. [2019]Beta cell replacement is a potential cure for type 1 diabetes. In humans, islet transplants are currently infused into the liver via the portal vein, although this site has disadvantages. Here, we investigated alternative transplantation sites for human and murine islets in recipient mice, comparing the portal vein with quadriceps muscle and kidney, liver and spleen capsules.
Replenishable prevascularized cell encapsulation devices increase graft survival and function in the subcutaneous space. [2023]Beta cell replacement therapy (BCRT) for patients with type 1 diabetes (T1D) improves blood glucose regulation by replenishing the endogenous beta cells destroyed by autoimmune attack. Several limitations, including immune isolation, prevent this therapy from reaching its full potential. Cell encapsulation devices used for BCRT provide a protective physical barrier for insulin-producing beta cells, thereby protecting transplanted cells from immune attack. However, poor device engraftment posttransplantation leads to nutrient deprivation and hypoxia, causing metabolic strain on transplanted beta cells. Prevascularization of encapsulation devices at the transplantation site can help establish a host vascular network around the implant, increasing solute transport to the encapsulated cells. Here, we present a replenishable prevascularized implantation methodology (RPVIM) that allows for the vascular integration of replenishable encapsulation devices in the subcutaneous space. Empty encapsulation devices were vascularized for 14 days, after which insulin-producing cells were inserted without disrupting the surrounding vasculature. The RPVIM devices were compared with nonprevascularized devices (Standard Implantation Methodology [SIM]) and previously established prevascularized devices (Standard Prevascularization Implantation Methodology [SPVIM]). Results show that over 75% of RPVIM devices containing stem cell-derived insulin-producing beta cell clusters showed a signal after 28 days of implantation in subcutaneous space. Notably, not only was the percent of RPVIM devices showing signal significantly greater than SIM and SPVIM devices, but the intraperitoneal glucose tolerance tests and histological analyses showed that encapsulated stem-cell derived insulin-producing beta cell clusters retained their function in the RPVIM devices, which is crucial for the successful management of T1D.
Long-term Functioning of Allogeneic Islets in Subcutaneous Tissue Pretreated With a Novel Cyclic Peptide Without Immunosuppressive Medication. [2022]There exists a need for a minimally invasive method of islet transplantation without immunosuppressive drugs for the treatment of type 1 diabetes.
A prevascularized subcutaneous device-less site for islet and cellular transplantation. [2021]Transplantation of donor-derived islets into the liver is a successful cellular replacement therapy for individuals with diabetes. However, the hepatic vasculature is not an optimal transplant site for several reasons, including graft attrition and the inability to retrieve or image the islets. Here we describe islet transplantation into a prevascularized, subcutaneous site created by temporary placement of a medically approved vascular access catheter. In mice with streptozotocin (STZ)-induced diabetes, transplantation of ∼500 syngeneic islets into the resulting 'device-less' space reversed diabetes in 91% of mice and maintained normoglycemia for >100 days. The approach was also effective in mice with pre-existing diabetes, in another mouse strain that mounts a more vigorous inflammatory response, and across an allogeneic barrier. These results demonstrate that transient priming of a subcutaneous site supports diabetes-reversing islet transplantation in mouse models without the need for a permanent cell-encapsulation device.
Effect of sirolimus-eluting stent in diabetic patients with small coronary arteries (a SES-SMART substudy). [2016]Randomized clinical trials have shown that sirolimus-eluting stents (SESs) decrease restenosis rates compared with bare metal stents (BMSs), but their efficacy among patients who have diabetes mellitus remains to be established. This study investigated the effect of SES implantation in a high-risk population (i.e., patients who had diabetes and small coronary vessel disease). For this purpose, we analyzed outcomes of the subset of patients who had diabetes and were enrolled in the SES-SMART, a randomized trial that compared the results of implantation of SESs and BMSs in small coronary arteries. Twenty-nine patients who had diabetes were originally randomized to receive SESs and 45 patients received BMSs. The use of SESs was associated with approximately 60% decreases in the relative incidence of in-segment angiographic restenosis (63% vs 25%, p = 0.003) and in-segment late loss (0.76 vs 0.28 mm, p
Long-term clinical benefit of sirolimus-eluting stent implantation in diabetic patients with de novo coronary stenoses: long-term results of the DIABETES trial. [2018]Sirolimus stent implantation has been demonstrated to be safe and effective in diabetics; however, the long-term outcomes in this high-risk population remain unknown. The aim of this study was to determine the long-term safety and efficacy of the sirolimus-eluting stent (SES) when compared with the bare metal stent (BMS) in patients included in the DIABETES (DIABETes and sirolimus Eluting Stent) trial.
Comparison of clinical outcomes between first-generation and second-generation drug-eluting stents in type 2 diabetic patients. [2013]Drug-eluting stent (DES) implantation has significantly reduced the risk of restenosis and major adverse cardiac event (MACE) rates compared with bare-metal stents in type 2 diabetic patients. Differences in outcomes between the first-generation and second-generation DESs in diabetic patients, however, have yet to be evaluated.
Drug-eluting or bare-metal stenting in patients with diabetes mellitus: results from the Massachusetts Data Analysis Center Registry. [2020]Patients with diabetes mellitus (DM) are at high risk for restenosis, myocardial infarction, and cardiac mortality after coronary stenting, and the long-term safety of drug-eluting stents (DES) relative to bare-metal stents (BMS) in DM is uncertain. We report on a large consecutive series of patients with DM followed up for 3 years after DES and BMS from a regional contemporary US practice with mandatory reporting.
Amphilimus- Versus Everolimus-Eluting Stents in Patients With Diabetes Mellitus: 5-Year Follow-Up of the RESERVOIR Trial. [2022]The amphilimus-eluting stent (AES) is a thin-strut polymer-free stent that releases sirolimus formulated with a carrier from abluminal grooves. The RESERVOIR trial compared AES vs everolimus-eluting stents (EES) in patients with diabetes mellitus (DM) and showed non-inferior neointimal hyperplasia suppression at 9 months follow-up. The aim of this study was to assess comparative clinical outcomes at 5 years. The endpoints analyzed for this extended follow-up were target-vessel failure (TVF), target-vessel revascularization (TVR) and target-lesion revascularization (TLR). At 5-years, AES vs EES had similar risk of TVF (HR 0.54, 95% CI 0.20-1.47, p = 0.23), TVR (HR 0.36, 95% CI 0.12-1.14, p = 0.08) and TLR (HR 0.43, 95%CI 0.11-1.67, p = 0.22). Landmark analyses between 1 and 5 years also showed no significant differences between groups.
Islet transplantation in the subcutaneous space achieves long-term euglycaemia in preclinical models of type 1 diabetes. [2021]The intrahepatic milieu is inhospitable to intraportal islet allografts1-3, limiting their applicability for the treatment of type 1 diabetes. Although the subcutaneous space represents an alternate, safe and easily accessible site for pancreatic islet transplantation, lack of neovascularization and the resulting hypoxic cell death have largely limited the longevity of graft survival and function and pose a barrier to the widespread adoption of islet transplantation in the clinic. Here we report the successful subcutaneous transplantation of pancreatic islets admixed with a device-free islet viability matrix, resulting in long-term euglycaemia in diverse immune-competent and immuno-incompetent animal models. We validate sustained normoglycaemia afforded by our transplantation methodology using murine, porcine and human pancreatic islets, and also demonstrate its efficacy in a non-human primate model of syngeneic islet transplantation. Transplantation of the islet-islet viability matrix mixture in the subcutaneous space represents a simple, safe and reproducible method, paving the way for a new therapeutic paradigm for type 1 diabetes.