Diabetes Mellitus, Type I Clinical Trial
Official title:
Open Randomized Mult-Center Study to Evaluate Safety and Efficacy of Low Molecular Weight Sulfated Dextran in Islet Transplantation (CIT-01)
Verified date | September 2021 |
Source | National Institute of Allergy and Infectious Diseases (NIAID) |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 24 |
Est. completion date | August 21, 2014 |
Est. primary completion date | July 2013 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility | Inclusion Criteria: - 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. Exclusion Criteria: - 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; - Baseline Hgb below the lower limits of normal, lymphopenia, neutropenia, or thrombocytopenia; - Activated protein C resistance (APC-R); - Any coagulopathy or individuals with an INR greater than 1.5; - Severe coexisting cardiac disease, characterized by any one of the following conditions: - Heart attack within the last 6 months, - Evidence of ischemia on functional heart exam within the year prior to study entry, or - Left ventricular ejection fraction less than 30%. - Persistent elevation of liver function tests at the time of study entry; - Acute or chronic pancreatitis; - Active peptic ulcer disease, symptomatic gallstones, or a history of portal hypertension; - Severe unremitting diarrhea, vomiting, or other gastrointestinal disorders that could interfere with the ability to absorb oral medications; - Currently receiving treatment for a medical condition that requires chronic use of systemic steroids; - Treatment with any antidiabetic medication other than insulin, within 4 weeks prior to study entry; - Use of any investigational medications within the past 4 weeks; - Received a live attenuated vaccine within the past 2 months; - Treatment with any immunosuppressive regimen at time of study entry; - Previous islet transplant; - Previous pancreas transplant. --Note: Participants who had a pancreas transplant more than 6 months prior to study entry that failed within the first week due to thrombosis, followed by surgical removal of the transplanted pancreas, are not excluded. - Or any medical condition that, in the opinion of the investigator, might interfere with safe participation. |
Country | Name | City | State |
---|---|---|---|
Norway | University Hospital Rikshospitalet | Oslo | |
Sweden | Karolinska University Hospital | Stockholm | |
Sweden | Uppsala University Hospital | Uppsala |
Lead Sponsor | Collaborator |
---|---|
National Institute of Allergy and Infectious Diseases (NIAID) | Clinical Islet Transplantation Consortium, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
Norway, Sweden,
von Zur-Mühlen B, Lundgren T, Bayman L, Berne C, Bridges N, Eggerman T, Foss A, Goldstein J, Jenssen T, Jorns C, Morrison Y, Rydén M, Schwieger T, Tufveson G, Nilsson B, Korsgren O. Open Randomized Multicenter Study to Evaluate Safety and Efficacy of Low — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Number of participants who achieve and maintain a 7.0% HbA1c level | Throughout Study | ||
Secondary | Number of severe hypoglycemic events | Throughout study | ||
Secondary | Percent reduction in insulin requirements | At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion | ||
Secondary | Ryan hypoglycemia severity score ( HYPO) score | : At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion | ||
Secondary | Proportion of participants with full graft function | At 70 to 80 days after first islet transfusion and after the final islet infusion | ||
Secondary | C-peptide to glucose creatinine ratio | At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion | ||
Secondary | Proportion of participants receiving a second islet infusion and proportion of participants receiving a third islet transfusion | At 70 to 80 days after first islet transfusion and after the final islet infusion | ||
Secondary | Incidence and severity of adverse events related to islet infusion procedure | At 70 to 80 days and 350 to 379 days after the first islet transfusion | ||
Secondary | Incidence of worsening retinopathy | At 350 to 379 days after the first islet transfusion | ||
Secondary | HbA1c level | At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion | ||
Secondary | Mean amplitude of glycemic excursions (MAGE) | At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion | ||
Secondary | Glycemic lability index (LI) | At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion | ||
Secondary | Clarke hypoglycemia awareness score | At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion | ||
Secondary | Basal (fasting) and 90-minute glucose and c-peptide derived from MMTT | : At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion | ||
Secondary | Beta-score | At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion | ||
Secondary | Acute insulin response to glucose, insulin sensitivity, and disposition index derived from the insulin-modified frequently-sampled intravenous glucose tolerance (FSIGT) test, | At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion | ||
Secondary | Glucose variability and hypoglycemic duration derived from continuous glucose monitoring system(CGMS) | At 70 to 80 days after first islet transfusion, At 365 days after first and final islet infusion | ||
Secondary | Incidence of a change in the immunosuppression drug regimen | At 70 to 80 days and 350 to 379 days after the first islet transfusion | ||
Secondary | Incidence of immune sensitization defined by detecting anti-HLA antibodies not present prior to transplantation | At 70 to 80 days and 350 to 379 days after the first islet transfusion |
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