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

NCT00790439 | Withdrawn Phase 2 DMC

• 2 other identifiers: DAIT CIT-01BCIT-01B
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Diabetes Mellitus, Type I

Keywords

Insulin dependence

Outcome Measures

Primary Outcomes (1)

• Level of Stimulated C-peptide at 90-minutes in Response to a Mixed-Meal Tolerance Test (MMTT)

  75 days following the first islet transplantation

Secondary Outcomes (5)

• Incidence and Severity of Adverse Events Related to the Islet Transplantation Procedure

  75 days and 365 days following the first islet transplantation

• Incidence and Severity of Adverse Events Related to the Immunosuppression

  75 days and 365 days following the first islet transplantation

• Incidence of Immune Sensitization Defined by Detecting Anti-HLA (Human Leukocyte Antigen) Antibodies not present prior to transplantation

  75 days and 365 days following the first islet transplantation

• Incidence of a Change in the Immunosuppression Drug Regimen

  75 days and 365 days following the first islet transplantation

• Incidence of Worsening Retinopathy

  365 days following the first islet transplantation

Study Arms (2)

LMW-SD

EXPERIMENTAL

18 participants randomized to immunosuppression with Low Molecular Weight Sulfated Dextran (LMW-SD)

Drug: Low Molecular Weight Sulfated Dextran; Drug: Mycophenolate Mofetil; Drug: Sirolimus; Drug: Tacrolimus; Drug: Cyclosporine; Drug: Daclizumab; Drug: Basiliximab; Biological: Allogeneic Pancreatic Islet Cells

Control Group, Standard of Care

ACTIVE COMPARATOR

18 participants randomized to immunosuppression without Low Molecular Weight Sulfated Dextran (LMW-SD)

Drug: Heparin; Drug: Mycophenolate Mofetil; Drug: Sirolimus; Drug: Tacrolimus; Drug: Cyclosporine; Drug: Daclizumab; Drug: Basiliximab; Biological: Allogeneic Pancreatic Islet Cells

Interventions

Low Molecular Weight Sulfated Dextran DRUG

Inhibitor of instant blood-mediated inflammatory reaction

Also known as: LMW-SD

LMW-SD

Heparin DRUG

Anticoagulant

Also known as: Heparin Sodium

Control Group, Standard of Care

Mycophenolate Mofetil DRUG

Cell proliferation inhibitor, Transplantation (immunosuppressive)

Also known as: MMF, Mycophenolate, Mycophenolic Acid, CellCept

Control Group, Standard of Care; LMW-SD

Sirolimus DRUG

Cell proliferation inhibitor, immunologic (immunosuppressive)

Also known as: Rapamune

Control Group, Standard of Care; LMW-SD

Tacrolimus DRUG

Calcineurin inhibitor

Also known as: Hecoria

Control Group, Standard of Care; LMW-SD

Cyclosporine DRUG

Calcineurin inhibitor, immunosuppressant

Also known as: Ciclosporin, GENGRAF® Capsules

Control Group, Standard of Care; LMW-SD

Daclizumab DRUG

Monoclonal IL-2 receptor blocker

Control Group, Standard of Care; LMW-SD

Basiliximab DRUG

Monoclonal IL-2 receptor blocker

Also known as: Simulect ®

Control Group, Standard of Care; LMW-SD

Allogeneic Pancreatic Islet Cells BIOLOGICAL

Control Group, Standard of Care; LMW-SD

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• Recent myocardial infarction (\<=6 months)

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Related Links

• Click here for the Clinical Islet Transplantation Consortium Web site
• National Institute of Allergy and Infectious Diseases (NIAID)

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Heparin; Mycophenolic Acid; Sirolimus; Tacrolimus; Cyclosporine; Cyclosporins; Daclizumab; Basiliximab

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Olle Korsgren, MD

  Department of Oncology, Radiology, and Clinical Immunology, Rudbeck Laboratory, Uppsala University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2008
• First Posted: November 13, 2008
• Study Start: July 1, 2008
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: June 12, 2014

Record last verified: 2014-06