Adrenergic System in Islet Transplantation
Last updated on July 2021Recruitment
- Recruitment Status
- Active, not recruiting
- Estimated Enrollment
- 45
Summary
- Conditions
- Hypoglycemia
- Hypoglycemia Unawareness
- Islet Cell Transplantation
- Type1diabetes
- Type
- Interventional
- Phase
- Early Phase 1
- Design
- Allocation: RandomizedIntervention Model: Factorial AssignmentIntervention Model Description: This study is a within subject and across group mechanistic design. Islet cell hormonal responses to a hyperinsulinemic euglycemic-hypoglycemic clamp will be assessed in "Group 1" on three occasions with randomized, double-blind administration of the ?-adrenergic blocker phentolamine, the ?-adrenergic blocker propranolol, or placebo. Responses in "Group 1" under the placebo condition will be used for comparison to those obtained from hyperinsulinemic euglycemic-hypoglycemic clamp testing on one occasion in subjects in each of "Group 2" and "Group 3".Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Masking Description: Conditions of testing for "Group 1" (intra-hepatic islet recipients) will remain double-blind for each subject until their completion of all testing visits, unless for safety concerns, either the PI or Medical Monitor request an unblinding. Groups "2" and "3" will have no masking.Primary Purpose: Basic Science
Participation Requirements
- Age
- Between 21 years and 65 years
- Gender
- Both males and females
Description
This study is designed to test the hypothesis that ?-adrenergic (neural) blockade will abolish insulin-mediated suppression of C-peptide, attenuating ?-cell glucagon secretion during hypoglycemia, and that ?-adrenergic (hormonal) blockade will have no effect. Glucose counterregulatory responses will...
This study is designed to test the hypothesis that ?-adrenergic (neural) blockade will abolish insulin-mediated suppression of C-peptide, attenuating ?-cell glucagon secretion during hypoglycemia, and that ?-adrenergic (hormonal) blockade will have no effect. Glucose counterregulatory responses will be measured during hyperinsulinemic euglycemic-hypoglycemic clamps on three occasions with randomized, double-blind administration of the ?-adrenergic blocker phentolamine, the ?-adrenergic blocker propranolol, or placebo. The demonstration of neural rather than hormonal regulation of the transplanted islet cell response to hypoglycemia is critical for understanding the mechanism for protection from hypoglycemia afforded by intrahepatically transplanted islets. Glucose counterregulation has not been studied in type 1 diabetic recipients of extrahepatic islet transplantation. Comparison of glucose counterregulatory responses measured during hyperinsulinemic euglycemic-hypoglycemic clamps will be compared to those obtained from type 1 diabetic recipients of intrahepatic islet transplantation studied under the placebo condition above. Glucose counterregulation has not been directly compared between recipients of intrahepatic auto- and allo-islet transplantation. Direct comparison of glucose counterregulatory responses under the same experimental conditions is required to understand whether mechanisms other than the glucagon response may be important to the reported hypoglycemia affecting pancreatectomized recipients of islet auto-transplantation.
Tracking Information
- NCT #
- NCT03079921
- Collaborators
- National Institutes of Health (NIH)
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Investigators
- Principal Investigator: Michael R Rickels, MD., MS Division of Endocrinology, Diabetes & Metabolism, Perelman School of Medicine
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