• Hyperglycemia/Hypoglycemia
• Diabetes Mellitus
• Diabetes & Endocrinology Clinical Trials

• Endocrinology
• Diabetes & Metabolic Syndrome
• Hyperglycemia/Hypoglycemia
• Diabetes Mellitus
• Diabetes & Endocrinology Clinical Trials

Preliminary data from the Islet Transplantation in Type 1 Diabetes study [NCT00434811] were presented by Bernhard J. Hering, MD, University of Minnesota, Minneapolis, Minnesota, USA. The Phase 3, open-label, single-group study was conducted by the Clinical Islet Transplantation (CIT) Consortium. The CIT was created by the National Institutes of Health to advance islet transplantation for patients with type 1 diabetes mellitus (T1DM) and severe hypoglycemia (SH) and patients who have had a kidney transplant.

A total of 8 centers enrolled 48 patients (aged 18 to 65 years) with a diabetes duration of 5 years or longer, an absence of stimulated C-peptide (< .3 ng/mL), 1 or more episodes of SH in the previous year, and either documented hypoglycemia unawareness or marked glycemic lability. Patients received up to 3 intraportal infusions of purified human pancreatic islets (PHPI) within an 8-month period. Induction immunotherapy included rabbit anti-thymocyte globulin and etanercept, and maintenance immunosuppression consisted of sirolimus and tacrolimus.

Dr. Hering reported secondary efficacy and safety outcomes. The primary outcome—the proportion of patients with an HbA1C less than 7.0% at Day 365 and free of hypoglycemic events from Day 28 to Day 365 inclusive following the first islet transplant—has been submitted for publication. All 48 patients have reached the 1-year follow-up after the initial islet transplant for the primary endpoint evaluation. Of these, 26 received a second transplant and 1 patient received 3 transplants.

The mean dose was 806,587 islet equivalents (IEQs), and the mean number of IEQs per kilogram of body weight was 11,476 in the 48 patients overall. In the patients who received only 1 islet treatment, the mean dose was 589,101 IEQs, and the mean number of IEQs per kilogram of body weight was 8372.

Evidence of islet graft function was found in approximately 95% of patients at Day 75 and approximately 90% at Day 365, as measured by C-peptide. At Day 365, 50% of patients were insulin-independent (insulin could only be given between Days 75 and 240).

Insulin requirements fell from a median at baseline of approximately 0.49 U/kg/day to a median of 0.00 U/kg/day (range, 0.00 to −0.43 U/kg/day) at Day 365 and were sustained to Day 730. C-peptide secretion increased in response to a mixed-meal tolerance test to a median 4 ng/mL at 90 minutes on Day 365, while glucose concentrations decreased to a median of approximately 150 ng/mL at Day 365. Awareness of hypoglycemia was significantly improved as measured by the Clarke Score (median 6 at baseline reduced to 0 at Day 365; p< .001) and the Ryan Hypoglycemia Score (p< .001). The Glycemic Lability Index decreased from approximately 800 at baseline to approximately 100 at Day 365 (p< .001) and the Mean Amplitude of Glycemic Excursions Score improved (p< .0002). The median percentage of time in glucose range (50 to 180 mg/dL) was approximately 95% at Day 365.

There were no deaths or permanent morbidities related to the study treatment. There were 19 serious adverse events, of which 5 were related to the procedure, 13 to immunosuppression, and 1 to insulin-related hypoglycemia. Other adverse events involved 6 patients with non-zero calculated panel reactive antibodies (only 1 was donor specific) and 1 patient with an acute kidney injury of unknown origin. The initiation of islet therapy transplantation was associated with a small but significant decrease in glomerular filtration rate (–8.1 mL/minute; p< .0001), with no further significant change at Days 75 and 365.

In summary, transplanted PHPI safely restored and then sustained glycemic control to near normal levels and provided protection against SH in patients with T1DM.

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