a study on Diabetes Type 1
The goal of this trial is to gain initial clinical experience regarding the safety and efficacy of treating type I diabetes in people who have received a kidney transplant by transplanting islets into a new transplant site in the stomach (gastrointestinal submucosa). A total of 6 patients will be enrolled in the study and followed for a period of 3 years after the last islet transplant.
Pancreatic islet transplantation offers a minimally invasive approach to restore normoglycemia in type 1 diabetics while avoiding the hypoglycemic complications observed with intensive insulin therapy and the surgical complications associated with pancreas transplantation. Although significant progress has been made in clinical islet transplantation, overall outcomes remain suboptimal since many patients lose insulin independence a few years after transplantation and multiple donors are usually needed to achieve independence. The cause of this progressive loss of function is multifactorial, but mounting evidence suggests that much of the islet loss after transplant is directly related to the intraportal transplant site that is used in clinical islet transplantation. Intravascular infusion of the islets triggers a severe,non-specific inflammatory response (immediate blood-mediated inflammatory reaction, IBMIR) which destroys at least 50% of the islet mass. The engraftment of the surviving islets is further compromised by the relatively hypoxic portal venous environment, and the infused islets are exposed to potentially toxic levels of immunosuppressive agents being absorbed from the gut into the portal circulation. Together, these characteristics contribute to early as well as late loss of islet function after transplantation. The gastrointestinal submucosa is a newly described transplant site that can support islet engraftment while avoiding many of the drawbacks associated with intraportal infusion. In addition, this site is easily accessible via upper endoscopy and the submucosal injection procedure is safe and technically straightforward.
The aim of this prospective, single-center trial is to provide initial clinical experience regarding the safety and efficacy of endoscopic gastric and duodenal submucosal islet transplantation in type I diabetic patients with kidney allografts. A total of 6 patients will be recruited into the trial. The investigators will follow the standardized islet manufacturing protocols and the thymoglobulin-based induction immunosuppressive regimen developed by the Clinical Islet Transplant consortium (CIT). Outcomes will include safety measures, glycemic control and insulin use, metabolic assessments of graft function, allo/auto-immune responses, and protocol biopsies to assess graft rejection/inflammation. The investigators believe that this novel approach to islet transplantation has the potential to significantly improve current islet transplantation outcomes by enhancing islet engraftment and long-term function.
Diabetes Mellitus, Type 1 Type 1 diabetes diabetes mellitus pancreatic islet transplant beta cell replacement Pancrelipase Pancreatin
Open to people ages 18–70
Reduced awareness of hypoglycemia manifested a Clarke score>4 and at least 1 episode of severe hypoglycemia in the past 12 months prior to study enrollment. This criterion requires that there has been involvement in intensive diabetes management under the direction of an endocrinologist, diabetologist, or diabetes specialist prior to study enrollment. Intensive diabetes management is defined as self-monitoring of glucose values no less than 3 times each day averaged over each week and by the administration of three or more insulin injections each day or insulin pump therapy. Severe hypoglycemia is defined as an event with one of the following symptoms: memory loss; confusion; uncontrollable behavior; irrational behavior; unusual difficulty in awakening; suspected seizure; seizure; loss of consciousness; or visual symptoms, and which was associated with either a BG level <54 mg/dl [3.0 mmol/L] or prompt recovery after oral carbohydrate, IV glucose, or glucagon administration.
OR In any subject not meeting the hypoglycemia option, a HbA1c ≥ 7.5 despite intensive diabetes management as defined above.
Calculated panel-reactive anti-HLA antibodies> 50%. Subjects with calculated panel reactive anti-HLA antibodies ≤ 50% will be excluded if any of the following are detected:
Severe co-existing cardiac disease, characterized by any one of these conditions:
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