NCT00789308

Safety and Effectiveness of Low Molecular Weight Sulfated Dextran in Islet Transplantation

Open Randomized Mult-Center Study to Evaluate Safety and Efficacy of Low Molecular Weight Sulfated Dextran in Islet Transplantation (CIT-01)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

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 effectiveness of low molecular weight sulfated dextran (LMW-SD) on post-transplant islet function in people with type 1 diabetes who have responded to intensive insulin therapy.

Detailed description

Type I diabetes, also known as insulin-dependent diabetes, is a chronic disease in which the pancreas produces insufficient insulin to properly regulate blood sugar levels. Hypoglycemia, or low blood sugar, and hyperglycemia, or high blood sugar, can lead to significant complications in people with type 1 diabetes. Intensive insulin therapy has been shown to reduce the risk of chronic complications in people who achieve near normalization of glycemia. However, this therapy is labor intensive, difficult to implement, and associated with an increased frequency of severe hypoglycemia. Transplantation of islets from a healthy pancreas has been successful in restoring normal blood sugar levels and has led to initial insulin independence in people with type 1 diabetes. Rejection of these islets by the recipient's immune system, however, can make the treatment ineffective. An immune response known as instant blood-mediated inflammatory reaction (IBMIR) results in the disruption of islet integrity and islet loss within an hour of transfusion. LMW-SD inhibits IBMIR by preventing the cascade that triggers it, when combined with pancreatic islets. The purpose of this study is to determine the safety and efficacy of LMW-SD given with islet transfusion and post-transfusion along with immunosuppressive therapy, including mycophenolate mofetil or sirolimus, tacrolimus or cyclosporine, and thymoglobulin or basiliximab, on the success of islet transplantation in people with type 1 diabetes. This study will last for 1 year after the final islet transplant. Participants may receive up to 3 islet transplants while participating in this study. Participants eligible for this study will have clinic visits every 6 months. Once a preparation of islets becomes available, participants will be randomly assigned to Arm 1 or Arm 2. Participants in Arm 1 will receive LMW-DS during and for 5 hours after infusion. Participants in Arm 2 will receive heparin at the time of infusion. In addition, all participants will receive anticoagulation prophylaxis agents consisting of Klexzane® (Enoxaparinsodium) and Trombyl® or Albyl-E® (Acetylsalicylic acid). All participants will also receive the oral immunosuppression medications consisting of mycophenolate mofetil or sirolimus and tacrolimus or cyclosporine throughout the study. In addition, they will receive intravenous thymoglobulin on days -2, -1, day 0 (transplant), +1, and +2 for the first transplant or intravenous basiliximab at the time of transplant and on Day 4 for the second and third transplant. Enbrel® (Etanercept) will be given to all participants for anti-inflammatory therapy. Islet infusions will occur at the hospital and will be given intravenously. Participants will be eligible to receive second and third islet infusions if previous infusions fail and they continue to meet the eligibility criteria. After each infusion, study visits will occur on Days 1, 3, 7, 14, 21, 28, and 75 and Months 6 and 12. At these visits, physical exams and blood collection will occur. At some visits, urine collection will also occur.

Conditions

• Diabetes Mellitus, Type I

Interventions

Type	Name	Description
DRUG	Low Molecular Weight Sulfated Dextran (LMW-SD)	Inhibitor of IBMIR
DRUG	Heparin	Anticoagulation
DRUG	CellCept® (Mycophenolate mofetil) OR Rapamune® (Sirolimus)	Cell proliferation inhibitor
DRUG	Prograf® (Tacrolimus) OR Cyclosporine	Calcineurin inhibitor
DRUG	Thymoglobulin® (Anti-thymocyte Globulin) - at first transplant
DRUG	Simulect® (Basiliximab) - at 2nd or 3rd transplant	Monoclonal IL-2 receptor blocker
DRUG	Klexane® (Enoxaparinsodium)	Anticoagulation Prophylaxis
DRUG	Trombyl® or Albyl-E® (Acetylsalicylicacid- ASA)	Anticoagulation Prophylaxis
DRUG	Enbrel® (Etanercept)	Anti-Inflammatory Therapy

Timeline

• Start date: 2008-07-11
• Primary completion: 2013-07-01
• Completion: 2014-08-21
• First posted: 2008-11-11
• Last updated: 2021-09-28

Locations

3 sites across 2 countries: Norway, Sweden