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

• Status: Withdrawn
• Trial end date: 2009-10-01
• Target enrollment: 0
• Participant gender: All

Summary

Type 1 diabetes mellitus (T1D) 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 T1D who have responded to intensive insulin therapy and have received kidney transplants. This study is taking place in Uppsala and Stockholm, Sweden, and Oslo, Norway.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Treatments: Basiliximab; Calcineurin Inhibitors; Calcium heparin; Cyclosporine; Cyclosporins; Daclizumab; Dextrans; Heparin; Mycophenolate mofetil; Mycophenolic Acid; Sirolimus; Tacrolimus

Criteria

Inclusion Criteria:

• Subjects able to provide written informed consent and comply with study procedures

• Clinical history compatible with T1D and onset of disease at less than 40 years of age and insulin dependence for more than (>) 5 years at the time of enrollment; AND the sum of subject age and insulin-dependent diabetes duration is >=28

• Absent stimulated C-peptide (less than 0.3 ng/mL) 60 and 90 minutes post-mixed-meal tolerance test (MMTT)

• Subjects >6 months post renal (kidney) transplant, currently taking or willing to switch to appropriate maintenance immunosuppression

• Stable renal function and free of rejection for >=3 months prior to islet transplantation

• Standard medical treatment for >=3 months under the care of an experienced diabetologist and at the end of this period has had at least 1 severe hypoglycemic event OR a hemoglobin A1C (HbA1c) >7.2% OR reduced awareness of hypoglycemia manifest by a Clark score of >=4 in the last year prior to study entry

Exclusion Criteria:

• Known immunoglobulin E (IgE) mediated allergy to antibiotics used in islet culture medium

• Known hypersensitivity to dextran

• Measured glomerular filtration rate (GFR) using Iothalmate, 51Cr-EDTA, 99-technetium-DPTA, or iohexol of less than 40ml/min/1.73 m^2

• Proteinuria (albuminuria greater than 500 mg in 24 hours) of new onset since kidney transplantation

• Other (non-kidney) organ transplants except prior failed pancreatic graft

• Body mass index (BMI) >30 kg/m^2

• Insulin requirement of >1.0 IU/kg/day

• Consistently abnormal liver function tests (aspartate aminotransferase(AST), alanine aminotransferase (ALT),alkaline phosphatase, or total bilirubin) of greater than 1.5 times the upper limit of normal for two consecutive measurements that are >2 weeks apart

• Untreated proliferative diabetic retinopathy

• History of hypercoagulability disorder or coagulopathy or International Normalized Ratio(INR) that is >1.5

• Activated Protein C Resistance (APC-R)

• Evidence by serologies and PCR of acute or chronic active Epstein-Barr Virus (EBV) infection OR no evidence by EBV serologies of prior EBV exposure

• Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin

• Known history of severe co-existing cardiac disease, characterized by any one of the following conditions:

1. Recent myocardial infarction (<=6 months)

2. Evidence of ischemia on functional cardiac exam <=last year

3. Left ventricular ejection fraction <30%

• Active infections, unless treatment is not judged necessary by the investigators(including but not limited to mild skin and nail fungal infections)

• Active infection including hepatitis B, hepatitis C,human immunodeficiency virus (HIV), or pulmonary tuberculosis

• Subjects with active peptic ulcer disease, symptomatic gallstones or portal hypertension

• Acute or chronic pancreatitis

• Subjects who are pregnant or breastfeeding, or who intend to become pregnant

• Sexually-active females who are not: a) post-menopausal, b) surgically sterile, or c) using an acceptable method of contraception: oral contraceptives, Norplant, Depo-Provera, and barrier devices combined with spermicidal gel are acceptable; condoms used alone are not acceptable.

• Active alcohol or substance abuse

• Evidence of high-level sensitization (Panel Reactive Antibodies (PRA) >50%) or positive cross match or the known presence of anti-donor HLA class I antibodies

• Treatment with any anti-diabetic medication, other than insulin, <=4 weeks of enrollment

• Use of any investigational agents <=4 weeks of enrollment

• Receipt of live attenuated vaccine(s) <=2 months of enrollment

• Subjects with any condition or circumstance that in the opinion of the investigator would make it unsafe to undergo an islet transplantation