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SAN FRANCISCO – Half of 48 adults with type 1 diabetes, impaired awareness of hypoglycemia, and a history of severe hypoglycemia were able to stop insulin therapy after experimental transplantation of human pancreatic islet cells in a prospective, phase III trial.
The National Institute of Health’s Clinical Islet Transplantation Consortium reported partial, initial results from 365 days of follow-up after islet-cell transplantation in the eight-center study. Speaking for the consortium at the annual scientific sessions of the American Diabetes Association, Dr. Bernhard J. Hering withheld results for the primary outcome measure (the proportion of patients who had a hemoglobin A1c of less than 7% at day 365 and no severe hypoglycemia in days 28 through 365 after the first islet transplant) pending its publication, he said.
Still, results for secondary measures of effectiveness and safety were good enough that "islet transplantation should be considered in this subgroup of patients when other treatment options have failed," said Dr. Hering, a professor of surgery and director of the Islet Cell Transplantation Program at the University of Minnesota, Minneapolis.
The study included patients who had had type 1 diabetes for at least 5 years, with stimulated C-peptide levels below 0.3 ng/mL (considered "absent") and at least one episode of severe hypoglycemia in the prior year with documentation of reduced hypoglycemia awareness and/or marked glycemic lability, if they didn’t meet any of 32 exclusion criteria. All patients underwent immunosuppression as part of the transplantation protocol.
Of the 48 patients, 26 received a second islet cell transplantation, and 1 received a third transplantation. Islet grafts were functioning in more than 90% of patients at day 365 of follow-up, he and his associates reported.
At day 365, roughly 50% of patients were insulin free. Insulin use decreased significantly to a median of 0 unit/kg per day at day 365.
Serum glucose levels and C-peptide secretion during mixed-meal tolerance tests improved over time after transplantation. Clarke scores and Ryan scores to assess patient awareness of hypoglycemia both improved significantly by day 365, as did measures of the glycemic lability index and the mean amplitude of glycemic excursions.
The median percentage of time spent within the desired glucose range increased from about 50% at baseline to nearly 95% at day 365, Dr. Hering reported.
The 19 serious adverse events included 5 that were procedure related (bleeding after percutaneous cannulation of a portal vein), 13 transient events related to immunosuppression (neutropenia, cytokine release, or elevated liver function test results), and 1 episode of hypoglycemia in a patient on insulin. None of these events caused death, disability, or permanent sequelae. Among other adverse events, a small but statistically significant drop in glomerular function test results was associated with the start of immunosuppression, six patients had calculated panel reactive antibodies above zero, and one patient developed acute kidney injury for unclear reasons.
The investigators plan further long-term follow-up.
Registry data suggest that approximately 35% of U.S. patients with type 1 diabetes each year report severe hypoglycemia requiring assistance, Dr. Hering said.
Dr. Hering has been a consultant for Novartis, Janssen, Novo Nordisk, Otsuka, and Sanofi.
On Twitter @sherryboschert
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This is another of the government-funded trials looking at clinical islet-cell transplantation, which are critically important because they have some success in some patients. This does offer promise for people who have hypoglycemia unawareness to the point where they are unable to function in their lives, but we need to find that out from the primary outcome results, which have not been presented. I would not use this treatment at this time.
The indication for islet-cell transplantation was severe hypoglycemia in someone with type 1 diabetes. This identifies a group that may have particular risks with standard therapy, in whom there may be justification for exposing them to the potential side effects of the transplant. That approach changes the risk-benefit ratio – that’s the way I interpret it.
The other exciting piece from this particular study is that it was a multisite project, and they had to do islet isolation at each site under standardized conditions, which is new. If we’re ever going to bring islet transplantation forward as a therapy and have it be approved by the Food and Drug Administration, there must be tremendous standardization in how islets are harvested and prepared for use. The fact that they were able to do that is very exciting.
Dr. Elizabeth R. Seaquist is a professor of medicine and the Pennock Family Chair in Diabetes Research at the University of Minnesota, Minneapolis. She gave these comments in an interview at the meeting. Dr. Seaquist is a colleague of Dr. Hering at the university. She reported financial associations with multiple companies but said none are relevant to this topic.
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This is another of the government-funded trials looking at clinical islet-cell transplantation, which are critically important because they have some success in some patients. This does offer promise for people who have hypoglycemia unawareness to the point where they are unable to function in their lives, but we need to find that out from the primary outcome results, which have not been presented. I would not use this treatment at this time.
The indication for islet-cell transplantation was severe hypoglycemia in someone with type 1 diabetes. This identifies a group that may have particular risks with standard therapy, in whom there may be justification for exposing them to the potential side effects of the transplant. That approach changes the risk-benefit ratio – that’s the way I interpret it.
The other exciting piece from this particular study is that it was a multisite project, and they had to do islet isolation at each site under standardized conditions, which is new. If we’re ever going to bring islet transplantation forward as a therapy and have it be approved by the Food and Drug Administration, there must be tremendous standardization in how islets are harvested and prepared for use. The fact that they were able to do that is very exciting.
Dr. Elizabeth R. Seaquist is a professor of medicine and the Pennock Family Chair in Diabetes Research at the University of Minnesota, Minneapolis. She gave these comments in an interview at the meeting. Dr. Seaquist is a colleague of Dr. Hering at the university. She reported financial associations with multiple companies but said none are relevant to this topic.
|
|
This is another of the government-funded trials looking at clinical islet-cell transplantation, which are critically important because they have some success in some patients. This does offer promise for people who have hypoglycemia unawareness to the point where they are unable to function in their lives, but we need to find that out from the primary outcome results, which have not been presented. I would not use this treatment at this time.
The indication for islet-cell transplantation was severe hypoglycemia in someone with type 1 diabetes. This identifies a group that may have particular risks with standard therapy, in whom there may be justification for exposing them to the potential side effects of the transplant. That approach changes the risk-benefit ratio – that’s the way I interpret it.
The other exciting piece from this particular study is that it was a multisite project, and they had to do islet isolation at each site under standardized conditions, which is new. If we’re ever going to bring islet transplantation forward as a therapy and have it be approved by the Food and Drug Administration, there must be tremendous standardization in how islets are harvested and prepared for use. The fact that they were able to do that is very exciting.
Dr. Elizabeth R. Seaquist is a professor of medicine and the Pennock Family Chair in Diabetes Research at the University of Minnesota, Minneapolis. She gave these comments in an interview at the meeting. Dr. Seaquist is a colleague of Dr. Hering at the university. She reported financial associations with multiple companies but said none are relevant to this topic.
SAN FRANCISCO – Half of 48 adults with type 1 diabetes, impaired awareness of hypoglycemia, and a history of severe hypoglycemia were able to stop insulin therapy after experimental transplantation of human pancreatic islet cells in a prospective, phase III trial.
The National Institute of Health’s Clinical Islet Transplantation Consortium reported partial, initial results from 365 days of follow-up after islet-cell transplantation in the eight-center study. Speaking for the consortium at the annual scientific sessions of the American Diabetes Association, Dr. Bernhard J. Hering withheld results for the primary outcome measure (the proportion of patients who had a hemoglobin A1c of less than 7% at day 365 and no severe hypoglycemia in days 28 through 365 after the first islet transplant) pending its publication, he said.
Still, results for secondary measures of effectiveness and safety were good enough that "islet transplantation should be considered in this subgroup of patients when other treatment options have failed," said Dr. Hering, a professor of surgery and director of the Islet Cell Transplantation Program at the University of Minnesota, Minneapolis.
The study included patients who had had type 1 diabetes for at least 5 years, with stimulated C-peptide levels below 0.3 ng/mL (considered "absent") and at least one episode of severe hypoglycemia in the prior year with documentation of reduced hypoglycemia awareness and/or marked glycemic lability, if they didn’t meet any of 32 exclusion criteria. All patients underwent immunosuppression as part of the transplantation protocol.
Of the 48 patients, 26 received a second islet cell transplantation, and 1 received a third transplantation. Islet grafts were functioning in more than 90% of patients at day 365 of follow-up, he and his associates reported.
At day 365, roughly 50% of patients were insulin free. Insulin use decreased significantly to a median of 0 unit/kg per day at day 365.
Serum glucose levels and C-peptide secretion during mixed-meal tolerance tests improved over time after transplantation. Clarke scores and Ryan scores to assess patient awareness of hypoglycemia both improved significantly by day 365, as did measures of the glycemic lability index and the mean amplitude of glycemic excursions.
The median percentage of time spent within the desired glucose range increased from about 50% at baseline to nearly 95% at day 365, Dr. Hering reported.
The 19 serious adverse events included 5 that were procedure related (bleeding after percutaneous cannulation of a portal vein), 13 transient events related to immunosuppression (neutropenia, cytokine release, or elevated liver function test results), and 1 episode of hypoglycemia in a patient on insulin. None of these events caused death, disability, or permanent sequelae. Among other adverse events, a small but statistically significant drop in glomerular function test results was associated with the start of immunosuppression, six patients had calculated panel reactive antibodies above zero, and one patient developed acute kidney injury for unclear reasons.
The investigators plan further long-term follow-up.
Registry data suggest that approximately 35% of U.S. patients with type 1 diabetes each year report severe hypoglycemia requiring assistance, Dr. Hering said.
Dr. Hering has been a consultant for Novartis, Janssen, Novo Nordisk, Otsuka, and Sanofi.
On Twitter @sherryboschert
SAN FRANCISCO – Half of 48 adults with type 1 diabetes, impaired awareness of hypoglycemia, and a history of severe hypoglycemia were able to stop insulin therapy after experimental transplantation of human pancreatic islet cells in a prospective, phase III trial.
The National Institute of Health’s Clinical Islet Transplantation Consortium reported partial, initial results from 365 days of follow-up after islet-cell transplantation in the eight-center study. Speaking for the consortium at the annual scientific sessions of the American Diabetes Association, Dr. Bernhard J. Hering withheld results for the primary outcome measure (the proportion of patients who had a hemoglobin A1c of less than 7% at day 365 and no severe hypoglycemia in days 28 through 365 after the first islet transplant) pending its publication, he said.
Still, results for secondary measures of effectiveness and safety were good enough that "islet transplantation should be considered in this subgroup of patients when other treatment options have failed," said Dr. Hering, a professor of surgery and director of the Islet Cell Transplantation Program at the University of Minnesota, Minneapolis.
The study included patients who had had type 1 diabetes for at least 5 years, with stimulated C-peptide levels below 0.3 ng/mL (considered "absent") and at least one episode of severe hypoglycemia in the prior year with documentation of reduced hypoglycemia awareness and/or marked glycemic lability, if they didn’t meet any of 32 exclusion criteria. All patients underwent immunosuppression as part of the transplantation protocol.
Of the 48 patients, 26 received a second islet cell transplantation, and 1 received a third transplantation. Islet grafts were functioning in more than 90% of patients at day 365 of follow-up, he and his associates reported.
At day 365, roughly 50% of patients were insulin free. Insulin use decreased significantly to a median of 0 unit/kg per day at day 365.
Serum glucose levels and C-peptide secretion during mixed-meal tolerance tests improved over time after transplantation. Clarke scores and Ryan scores to assess patient awareness of hypoglycemia both improved significantly by day 365, as did measures of the glycemic lability index and the mean amplitude of glycemic excursions.
The median percentage of time spent within the desired glucose range increased from about 50% at baseline to nearly 95% at day 365, Dr. Hering reported.
The 19 serious adverse events included 5 that were procedure related (bleeding after percutaneous cannulation of a portal vein), 13 transient events related to immunosuppression (neutropenia, cytokine release, or elevated liver function test results), and 1 episode of hypoglycemia in a patient on insulin. None of these events caused death, disability, or permanent sequelae. Among other adverse events, a small but statistically significant drop in glomerular function test results was associated with the start of immunosuppression, six patients had calculated panel reactive antibodies above zero, and one patient developed acute kidney injury for unclear reasons.
The investigators plan further long-term follow-up.
Registry data suggest that approximately 35% of U.S. patients with type 1 diabetes each year report severe hypoglycemia requiring assistance, Dr. Hering said.
Dr. Hering has been a consultant for Novartis, Janssen, Novo Nordisk, Otsuka, and Sanofi.
On Twitter @sherryboschert
AT THE ADA ANNUAL SCIENTIFIC SESSIONS
Key clinical point: You’ll have to wait for the primary results, but secondary outcomes suggest success with islet-cell transplantation in a subset of patients with type 1 diabetes.
Major finding: Half of patients were able to stop insulin within a year of transplantation.
Data source: A prospective, open-label, single-arm study of islet-cell transplantation in 48 adults with type 1 diabetes and a history of severe hypoglycemia and hypoglycemia unawareness.
Disclosures: Dr. Hering has been a consultant for Novartis, Janssen, Novo Nordisk, Otsuka, and Sanofi.
