67 Clinical Trials for Various Conditions
The primary objective of this protocol is to test the safety and efficacy of a treatment regimen consisting of maintenance therapy with efalizumab and sirolimus for 1 year followed by withdrawal of efalizumab and maintenance therapy with sirolimus, for the prevention of the destruction and rejection of islet transplants in type 1 diabetic recipients. Genentech, the manufacturer of efalizumab voluntarily withdrew the drug from the U.S. market in April of 2009. Previously transplanted subjects have been transitioned to alternative immunosuppressives and no new subjects will be transplanted under this protocol.
The complex program of insulin replacement for type 1 diabetes that is current clinical standard of care is difficult to implement for long periods of time, associated with an increased risk of severe hypoglycemia and implemented by less than 50 % of the population of such patients. Outcomes of transplantation of isolated human islets have substantially improved and been performed at about 40 institutions around the world. We are proposing a clinical phase 1/phase 2 study of islet transplantation alone evaluating safety and efficacy in five patients with type 1 diabetes. Islet isolation from deceased donor pancreases will be performed at the Mayo Rochester Islet Isolation facility and islets infused by Interventional Radiology into the portal venous system. Following islet infusion, patients will be hospitalized for 48 hours in the General Clinical Research Center (GCRC) or at the Rochester Methodist Hospital. Multiple safety and efficacy outcomes will be followed on multiple occasions during the first year and periodically thereafter.
Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed, resulting in poor blood sugar control. The purpose of this study is to assess the safety and efficacy of deoxyspergualin (DSG), an immunosuppressant drug, on post-transplant islet function in people with type 1 diabetes who have not responded to intensive insulin therapy.
Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed, resulting in poor blood sugar control. The purpose of this study is to determine the safety and effectiveness of islet transplantation, combined with immunosuppressive medications, for treating type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes.
The purpose of this study is to test whether the islet cell transplantation procedures and results from a previous study in Edmonton, Canada, can be repeated. The study also is designed to learn more about diabetes control using islet cell transplantation. This is a Phase I/II study (a study that examines effectiveness and looks for side effects). The transplanting of islet cells has been studied in Type 1 diabetic patients whose blood sugar levels will not stay normal, despite intensive insulin therapy. A recent study conducted in Edmonton, Canada, was able to demonstrate that islet transplantation led to insulin independence in a majority of the patients treated. This study extends the results obtained from the Edmonton study, which used islet transplantation in Type 1 diabetic patients with steroid-free immunosuppression.
This study will test whether a new islet transplant procedure will enable patients with type 1 diabetes mellitus to stop insulin therapy. Islets are cell clusters in the pancreas that contain insulin-producing cells. The new procedure features three important advances, first developed by a group in Edmonton, Canada, over the way islet transplants have traditionally been performed: 1) the islets are transplanted immediately after they are removed from the donor; 2) islets are transplanted from two different donors in order to obtain the number of islets in a normal pancreas; and 3) the anti-rejection drug regimen is designed to reduce the harmful side effects of "conditioning" chemotherapy. (In the standard transplant procedure, patients receive intensive chemotherapy following the transplant. This study will use no radiation and lower-dose chemotherapy.) Patients between the ages of 18 and 65 with the diagnosis of type 1 diabetes mellitus for at least 5 years may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood tests, chest X-ray and tuberculin skin test, electrocardiogram and exercise test for heart function, abdominal ultrasound, psychological evaluation, and an arginine stimulated c-peptide test. The latter test determines if the patient is producing any insulin. Eligibility is restricted to patients who make no insulin at all. The study has an active phase lasting 15 months and follow-up that continues indefinitely. Patients will receive 10,000 "islet equivalents" per kilogram (2.2 pounds) of body weight. This will likely require two separate transplant procedures from two donors. Before the first surgery, patients will be given anti-rejection (immune suppressing) drugs, including FK506 and rapamycin (orally) and daclizumab (intravenously). The islets will be infused through a tube placed in the portal vein (the large vein that feeds the liver). After surgery, patients will receive insulin intravenously for 24 hours. They will then have an abdominal ultrasound and blood tests to determine liver function. If fewer than 10,000 islets were transplanted, patients will continue insulin treatment, with the dosages adjusted to account for the transplanted islets. They will take Daclizumab every 2 weeks, and FK506 and rapamycin daily. Blood tests to follow how much of these drugs are in the blood stream will be performed daily at first and then weekly after blood levels of these drugs stabilize. They will be given antibiotics to prevent infections. The arginine test will be repeated 2 weeks after the transplant and periodically thereafter. Blood will be drawn weekly to check drug levels, and monthly for other tests. The investigators will track daily insulin requirements, and these will be recorded monthly. Patients who require a second transplant to achieve the required amount of islets will return for the procedure when a compatible organ is donated. The second procedure will be done as described above. As before, insulin will be infused for 24 hours following surgery. It will then be stopped, however, and will not be resumed unless blood glucose levels reach above 180 milligrams/deciliter. Patients will continue taking FK506 and rapamycin indefinitely. Daclizumab will be given every 2 weeks for 4 doses following the second transplant, and then stopped. Patients will take an antiviral called ganciclovir for 14 weeks and another antibiotic for 1 year following surgery. For the first year after surgery, patients will have frequent blood tests to monitor drug levels and immune function. They will return to NIH for a complete history and physical examination 2 and 3 years after the final islet transplant and will be contacted yearly by phone to ascertain their general health status and whether they remain insulin independent.
The purpose of this study is to provide patients who have received at least one islet transplant as a previous participant in a Clinical Islet Transplantation Consortium (CIT) clinical trial with maintenance immunosuppressive medications and to collect information about the safety of the medications and islet function.
City of Hope National Medical Center, located in Duarte, CA, is hosting a clinical study on islet cell transplantation, an experimental procedure being evaluated as a treatment for patients with type 1 diabetes. Islet cell transplantation involves taking insulin-producing cells from organ donors and transplanting them into the liver of a patient with diabetes. Once transplanted, the islets produce insulin, which can improve blood sugar control and eliminate the need to inject insulin or use an insulin pump. Anti-thymocyte globulin (ATG) and alemtuzumab (Campath) are anti-rejection medications that work by decreasing a patient's T-cells. T-cells are special white blood cells that recognize and destroy unwanted things like infections but can also attack transplanted cells and organs. Reducing the number of T-cells at the time of transplant may protect islets and improve long-term transplant success. In previous research studies, islet transplantation has been successful in reducing low blood sugar episodes, improving overall blood sugar control, and in some cases, allowing patients with type 1 diabetes to stop taking insulin. The purpose of this study is to determine if islet cell transplantation using ATG or alemtuzumab, along with additional medications to prevent the body from rejecting the transplanted cells, is a safe and effective treatment for type 1 diabetes. Study participants may receive up to three islet transplants and will be followed for five years to monitor blood sugar control, islet transplant function, and changes in quality of life.
Pancreatic islets are the part of the pancreas that produce insulin and help control the blood sugar. This study aims to improve islet transplantation as a treatment for Type 1 Diabetes by using a new combination of immunosuppressive drugs that have been successful in treating other autoimmune diseases and in preventing kidney transplant rejection.
The objective of this clinical trial was: - to assess whether Reparixin leads to improved transplant outcome as measured by glycaemic control following intra-hepatic infusion of pancreatic islets in patients with Type 1 diabetes (T1D). The safety of Reparixin in the specific clinical setting was also evaluated. Background: The chemokine CXCL8 plays a key role in the recruitment and activation of polymorphonuclear neutrophils in post-ischemia reperfusion injury after organ transplantation. Reparixin is the first low molecular weight blocker of CXCL8 biological activity in clinical development. Thus, the use of reparixin may emerge as a potential key component in the sequentially integrated approach to immunomodulation and control of non specific inflammatory events surrounding the early phases of pancreatic islet transplantation in T1D patients.
The primary objective of this study is to demonstrate the safety of allogenic islet transplantation in type 1 diabetic patients performed at the University of Virginia. The purpose is to demonstrate that islet transplantation can be performed safely and reliably achieves better glycemic control than state-of-the-art insulin treatment in management of type 1 diabetic patients with brittle control and a history of severe hypoglycemic episodes with hypoglycemia unawareness.
The purpose of this study is to determine if prolonged administration of the anti TNF (tumor necrosis factor)-Alpha agent etanercept is associated with enhanced graft survival in patients undergoing islet after kidney transplantation.
We hypothesize that the following improvements to islet transplantation will increase the islet mass successfully isolated and allow for engraftment from a single pancreas. The improvements are: * Using Two-Layer method preservation to improve pancreas quality before islet isolation * Maintaining isolated islets in culture before transplantation * Using a steroid-free immunosuppression regimen * Transplanting the best combination of donor and recipient possible after human leukocyte antigens (HLA) screening and final crossmatching
This protocol will test whether Type 1 diabetes (T1DM) can be reversed in patients with stable renal allografts by islet transplantation.
This clinical study will evaluate the safety and effectiveness of Gastrin treatment with islet transplantation to help patients with difficult to control type 1 diabetes make insulin again and improve blood sugar control. This study involves two investigational (experimental) products not yet approved by the U.S. Food and Drug Administration (FDA) as a treatment for any disease: 1. Human allogenic islet cells (islet cells from a deceased, unrelated human donor) 2. Gastrin-17 (Gastrin) - a hormone secreted by the gut
The purpose of this study is to learn about the safety of islet transplantation for Type 1 diabetes mellitus, which may provide more normal control of blood sugar without the need for insulin shots. Islets are special clusters of cells within the pancreas that produce insulin. These cells will be obtained from cadaver (non-living) donors and given to subjects by vein.
This protocol will provide islet cell transplantation to two separate populations in need of a pancreas transplant: Group I: Islet Cell Transplantation in Type I Diabetics without Kidney Problems Group II: Islet Cell Transplantation in Type I Diabetics Who Have a Stable Functioning Kidney Transplant The targeted patients have very brittle diabetes or dangerous hypoglycemic unawareness and may benefit from transplantation over continuing insulin therapy, even though chronic immunosuppression is required. We believe that in these patients, the islet transplant procedure promises enough potential benefit to justify subjecting patients who have not previously had a transplant to the risk of immunosuppression. In patients who are already subject to the dangers of chronic immunosuppression for other reasons, i.e. to prevent rejection of a kidney allograft, the islet transplantation procedure itself is the principal additional risk and this risk should be minimal. In these patients (our Group II), the potential benefit from improved glycemic control is that it promises to slow or even reverse diabetic complications, such as vascular problems leading to kidney damage. It is this rationale that has made pancreas transplantation a widely accepted option in patients with renal failure, despite the risks associated with whole pancreas transplantation. Islet cell transplantation aims to provide a potentially lower risk procedure that has similar relief from diabetic complications.
The purpose of this study is to reverse hyperglycemia and insulin dependency, by islet cell transplantation, in patients with type 1 diabetes mellitus who have a stable kidney allograft.
SPECIFIC AIMS: 1. To reverse hyperglycemia and insulin dependency in patients with Type 1 Diabetes Mellitus by islet cell transplantation; 2. To eliminate the incidence of hypoglycemia coma and unawareness in patients with Type 1 Diabetes Mellitus by islet cell transplantation; 3. To assess long-term safety and function of successful islet cell transplants in patients with Type 1 Diabetes Mellitus; 4. To determine whether the natural history of the microvascular, macrovascular and neuropathic complications of Diabetes Mellitus are altered following successful transplantation of islet cells; and 5. To assess the effect of infliximab in preventing early islet destruction, and thereby eliminating the need for a second donor's islet cells. 6. To assess the effect of etanercept in preventing early islet destruction. 7. To assess the effect of exenatide to improve islet graft function and survival in subjects that have returned to using exogenous insulin. 8. To assess the ability of exenatide to improve islet survival at time of transplantation.
The goal of islet cell transplantation in patients with Type 1 Diabetes Mellitus is to provide constant normal blood glucose levels. This may eliminate the need for insulin altogether or provide a significant reduction in the amount of insulin necessary to maintain constant normal blood glucose levels. This normalization may prevent or slow progression of diabetic complications. Furthermore, the participant may enjoy a healthier lifestyle and a better quality of life. If you meet the initial inclusion criteria for the trial, you must be able to give informed consent personally. Then you will need to participate in an extensive screening process that involves many standard tests and collection of laboratory samples to make sure that the transplant is suitable and safe for you.
The purpose of this study is to determine the safety of islet transplantation in patients with type 1 diabetes who have had a successful kidney transplant and have been maintained for at least three months on anti-rejection medications consisting of any combination of sirolimus, tacrolimus, MMF or prednisone (5 mg/day or less). Another purpose is to determine the effectiveness of an islet transplant in inducing insulin independence and whether or not an islet transplant improves quality of life for kidney transplants patients with type 1 diabetes.
AT-1501 is a monoclonal antibody. Antibodies are Y-shaped proteins that are produced naturally by the subject's immune system to attack and fight foreign substances that cause illness. Monoclonal antibodies are man-made proteins manufactured to serve as substitute antibodies to fight diseases. Monoclonal antibodies can restore, enhance, or mimic (copy) the immune system's attack process; they can also tone down the immune system. AT-1501 is thought to work by dampening down the immune system so that it will be less likely to attack the transplanted cells. For other types of transplants, like kidney, a drug called a calcineurin inhibitor is usually used to prevent rejection. That class of drugs can be toxic to islet cells. AT-1501 is an experimental agent that is anticipated to prevent rejection without harming the islet cells.
This study will evaluate the safety, tolerability and efficacy of AT-1501 in an immunomodulation regimen in adult patients with T1D undergoing an islet cell transplant.
A Phase 3 clinical trial has been completed and demonstrated the safety and efficacy of allogeneic islet transplantation in improving glycemic control in Type 1 diabetic patients using the UIC protocol.The objective in offering expanded access to donislecel (allogeneic islets of Langerhans for transplant; IND BB-11807) for the treatment of brittle T1D is to bridge the gap between completed clinical trials and marketing (i.e. approval by the FDA of a biological license application). Expanded access will allow clinical trial subjects, as well as patients outside a clinical trial, to receive treatment. New patients participating in the expanded access protocol are required to meet exclusion and inclusion criteria.
The Cell Pouch™ is a novel implantable device, that is transplanted with therapeutic cells such as insulin producing islets. This combination product is designed for the treatment of Type 1 Diabetes Mellitus (T1D) with hypoglycemia unawareness and a history of severe hypoglycemic episodes. Upon implantation, the Cell Pouch is designed to form a natural environment, rich in tissue and microvessels for the transplant and function of therapeutic cells. The Cell Pouch is designed as a scaffold made of non-degradable polymers, formed into small cylindrical chambers which, when implanted against the abdominal muscle, becomes incorporated with vascularized tissue to the circumference of removable plugs within as early as two weeks as demonstrated in preclinical studies. After the tissue incorporation, the plugs are removed, leaving fully formed tissue chambers with central void spaces for the transplantation of therapeutic cells including Islets of Langerhans (islets). Tissue integration within and around the Cell Pouch forms a natural environment, rich in microvessels that allows the transplanted islets to engraft, resulting in a functional biohybrid organ. It is believed this engraftment will enable long-term survival and function of transplanted islets. This study aims to demonstrate the safety and tolerability of islet transplantation into the Cell Pouch for the treatment of T1D in subjects with hypoglycemia unawareness and a history of severe hypoglycemic episodes. The study also aims to establish islet release criteria that accurately characterize the islet product and are predictive of clinical transplant outcomes into the Cell Pouch, which will be demonstrated through defined efficacy measures.
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 up to 3 years after the last islet transplant.
Protocol to screen potential subjects for islet transplantation
This is a single-center, prospective, open label study in islet transplant recipients following islet graft loss.
This is a single-center, prospective, open label study in islet transplant recipients after complete islet graft rejection/loss, defined as stimulated c-peptide ≤0.3 ng/mL.
Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed, resulting in poor blood sugar control. The purpose of this study is to determine the safety and effectiveness of islet transplantation, combined with immunosuppressive medications and medications to support islet survival for treating type 1 diabetes in individuals experiencing hypoglycemia unawareness and severe hypoglycemic episodes.