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

NCT00789308 | Completed Phase 2 DMC

• 3 other identifiers: DAIT CIT-01CIT-012008-001210-25
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 3

Brief 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.

Conditions

Diabetes Mellitus, Type I

Keywords

Insulin dependence

Outcome Measures

Primary Outcomes (1)

• Level of stimulated c-peptide at 90-minute derived from the mixed-meal tolerance test (MMTT)

  At 70 to 80 days after first islet transfusion

Secondary Outcomes (19)

• Number of participants who achieve and maintain a 7.0% HbA1c level

  Throughout Study

• Number of severe hypoglycemic events

  Throughout study

• Percent reduction in insulin requirements

  At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion

• Ryan hypoglycemia severity score ( HYPO) score

  : At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion

• Proportion of participants with full graft function

  At 70 to 80 days after first islet transfusion and after the final islet infusion

Study Arms (2)

Standard of Care

ACTIVE COMPARATOR

18 participants randomized to protocol immunosuppression (Daclizumab OR Basiliximab; Tacrolimus OR Cyclosporine; Mycophenolate Mofetil OR Sirolimus; and heparin) without LMW-DS

Drug: Heparin; Drug: CellCept® (Mycophenolate mofetil) OR Rapamune® (Sirolimus); Drug: Prograf® (Tacrolimus) OR Cyclosporine; Drug: Thymoglobulin® (Anti-thymocyte Globulin) - at first transplant; Drug: Simulect® (Basiliximab) - at 2nd or 3rd transplant; Drug: Klexane® (Enoxaparinsodium); Drug: Trombyl® or Albyl-E® (Acetylsalicylicacid- ASA); Drug: Enbrel® (Etanercept)

LMW-DS

EXPERIMENTAL

18 participants randomized to protocol immunosuppression (Daclizumab OR Basiliximab; Tacrolimus OR Cyclosporine; Mycophenolate Mofetil OR Sirolimus; and heparin) and LMW-DS

Drug: Low Molecular Weight Sulfated Dextran (LMW-SD); Drug: CellCept® (Mycophenolate mofetil) OR Rapamune® (Sirolimus); Drug: Prograf® (Tacrolimus) OR Cyclosporine; Drug: Thymoglobulin® (Anti-thymocyte Globulin) - at first transplant; Drug: Simulect® (Basiliximab) - at 2nd or 3rd transplant; Drug: Klexane® (Enoxaparinsodium); Drug: Trombyl® or Albyl-E® (Acetylsalicylicacid- ASA); Drug: Enbrel® (Etanercept)

Interventions

Low Molecular Weight Sulfated Dextran (LMW-SD) DRUG

Inhibitor of IBMIR

LMW-DS

Heparin DRUG

Anticoagulation

Standard of Care

CellCept® (Mycophenolate mofetil) OR Rapamune® (Sirolimus) DRUG

Cell proliferation inhibitor

LMW-DS; Standard of Care

Prograf® (Tacrolimus) OR Cyclosporine DRUG

Calcineurin inhibitor

LMW-DS; Standard of Care

Thymoglobulin® (Anti-thymocyte Globulin) - at first transplant DRUG

LMW-DS; Standard of Care

Simulect® (Basiliximab) - at 2nd or 3rd transplant DRUG

Monoclonal IL-2 receptor blocker

LMW-DS; Standard of Care

Klexane® (Enoxaparinsodium) DRUG

Anticoagulation Prophylaxis

LMW-DS; Standard of Care

Trombyl® or Albyl-E® (Acetylsalicylicacid- ASA) DRUG

Anticoagulation Prophylaxis

LMW-DS; Standard of Care

Enbrel® (Etanercept) DRUG

Anti-Inflammatory Therapy

LMW-DS; Standard of Care

Eligibility Criteria

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

You may qualify if:

• Mentally stable and able to comply with study procedures;
• Clinical history compatible with type 1 diabetes, with:
• onset of disease at less than 40 years of age,
• insulin dependence for at least 5 years at study entry, and
• sum of age and insulin-dependent diabetes duration of at least 28.
• Absent stimulated C-peptide (less than 0.3 ng/ml) 60 and 90 minutes post-mixed-meal tolerance test;
• Involvement of intensive diabetes management, defined as:
• Self-monitoring of glucose values no less than a mean of three times each day, averaged over each week,
• Administration of three or more insulin injections each day or insulin pump therapy,
• Under the direction of an endocrinologist, diabetologist, or diabetes specialist, with at least three clinical evaluations during the past 12 months.
• At least one episode of severe hypoglycemia in the past 12 months, defined as an event with symptoms compatible with hypoglycemia in which the individual required assistance of another person and which was associated with either a blood glucose level less than 54 mg/dl or prompt recovery after an oral carbohydrate, intravenous glucose, or glucagon administration; and
• Reduced awareness of hypoglycemia OR marked glycemic lability OR a composite of a Clarke score of 3 or more or a HYPO score greater or equal to the 75th percentile in the 12 months prior to randomization.

You may not qualify if:

• Known IgE mediated allergy to antibiotics used in the culture medium;
• Known hypersensitivity to dextran;
• Body mass index (BMI) greater than 30 kg/m\^2;
• Insulin requirement of more than 1.0 IU/kg/day;
• HbA1c greater than 10%;
• Untreated proliferative diabetic retinopathy;
• Systolic blood pressure higher than 160 mmHg or diastolic blood pressure higher than 100 mmHg;
• Measured glomerular filtration rate (GFR) using 51Cr-EDTA, 99technetium-DPTA, or iohexol of less than 80 ml/min/1.73m\^2;
• Presence or history of macroalbuminuria (greater than 300 mg/g creatinine);
• Presence or history of panel-reactive anti-HLA antibody levels greater than 20% by flow cytometry;
• Pregnant, breastfeeding, or unwilling to use effective contraception throughout the study and for 4 months after study completion;
• Active infection, including hepatitis B virus, hepatitis C virus, HIV, or tuberculosis;
• Negative for Epstein-Barr virus by IgG determination;
• History of malignancy with exception of completely resected squamous or basal cell carcinoma of the skin;
• Known active alcohol or substance abuse;

Sponsors & Collaborators

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

Study Sites (3)

University Hospital Rikshospitalet

Oslo, Norway

Location

Karolinska University Hospital

Stockholm, Sweden

Location

Uppsala University Hospital

Uppsala, Sweden

Location

Related Publications (1)

• von Zur-Muhlen B, Lundgren T, Bayman L, Berne C, Bridges N, Eggerman T, Foss A, Goldstein J, Jenssen T, Jorns C, Morrison Y, Ryden M, Schwieger T, Tufveson G, Nilsson B, Korsgren O. Open Randomized Multicenter Study to Evaluate Safety and Efficacy of Low Molecular Weight Sulfated Dextran in Islet Transplantation. Transplantation. 2019 Mar;103(3):630-637. doi: 10.1097/TP.0000000000002425.

  PMID: 30211831 RESULT

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Clinical Islet Transplantation Consortium website

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Heparin; Mycophenolic Acid; Sirolimus; Tacrolimus; Cyclosporine; thymoglobulin; Antilymphocyte Serum; Basiliximab; Etanercept

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; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Immunoglobulin Constant Regions; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Study Officials

• Olle Korsgren, MD

  Uppsala University Hospital, Sweden

  PRINCIPAL INVESTIGATOR

• Torbjörn Lundgren, MD

  Karolinska University Hospital

  STUDY CHAIR

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 11, 2008
• Study Start: July 11, 2008
• Primary Completion: July 1, 2013
• Study Completion: August 21, 2014
• Last Updated: September 28, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: On average, within 24 months after database lock for the trial.
• Access Criteria: Open access.

Locations

SE (2); NO (1)