B-Lymphocyte Immunotherapy in Islet Transplantation for Initial Islet Graft Failure

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 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.

Conditions

• Type 1 Diabetes Mellitus

Interventions

BIOLOGICAL

Allogeneic Pancreatic Islet Cells

200mL sterile suspension of allogeneic human pancreatic islets

DRUG

Sirolimus

Dosed to maintain whole blood 24-hr trough levels 10-15ng/mL for first 3 months and 8-12ng/mL thereafter daily. Sirolimus is used to prevent transplant rejection.

BIOLOGICAL

Basiliximab

20mg intravenously (IV) 2hrs prior to islet infusion and on Day 4 post-transplant. Basiliximab is used to prevent transplant rejection

DRUG

Tacrolimus

Initial dose of 0.015mg/kg p.o. daily on Day 1 post transplant, and adjusted to maintain 12-hr trough levels 3-6ng/mL. Tacrolimus lowers the risk of organ rejection

DRUG

Antibacterial, Antifungal, and Antiviral Prophylaxis

Broad spectrum antimicrobial prophylaxis administered preoperatively

DRUG

Trimethoprim/sulfamethoxazole

80mg/400mg by mouth once a day starting on Day 1 for duration of the study follow-up. This medication is used to prevent bacterial infections.

DRUG

Clotrimazole

1 troche by mouth 4 times daily starting two days prior to transplant until 3 months after the transplant. This medication is used to prevent fungal infections.

DRUG

Valganciclovir

450mg dose by mouth once a day starting two days pre-transplant and increasing to 900 mg once a day by Day 12 and continuing for 14 weeks post-transplant. This medication is used to prevent cytomegalovirus infections.

DRUG

Heparin

70U/kg body weight of recipient given with islet infusion, followed by 3U/kg/hr for the next 4hrs. From 5th through 48th hr post-transplant heparin will be titrated to achieve and maintain a Partial Thromboplastin Time (PTT) of 50-60 seconds. This medication is used to prevent the formation of blood clots.

DRUG

Enoxaparin

30mg subcutaneously twice a day from 48 hrs post-transplant through Day 7 post-transplant. This medication is used to prevent the formation of blood clots.

DRUG

Pentoxifylline

400mg slow release tablet by mouth three times a day beginning 2 days prior to transplant and continue for 7 days post transplant. This medication improves blood flow.

DRUG

Aspirin

81mg enteric coated aspirin by mouth every night, starting 24hrs post-transplant. This medication prevents blood clots.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  collaborator NIH

• National Institute of Allergy and Infectious Diseases (NIAID)

  lead NIH

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Countries

• United States

Study Locations