Clinical trial NCT03079921: Adrenergic System in Islet Transplantation
Official title: Adrenergic Contribution to Glucose Counterregulation in Islet Transplantation
Conditions: Type1diabetes
Hypoglycemia
Hypoglycemia Unawareness
Islet Cell Transplantation
Summary: To determine the effect of sympathetic neural and hormonal (epinephrine) input on islet cell hormonal responses to insulin-induced hypoglycemia in type 1 diabetic recipients of intrahepatic islet transplantation. We hypothesize that α-adrenergic (neural) blockage will abolish insulin-mediated suppression of C-peptide, attenuating α-cell glucagon secretion during hypoglycemia, and that β-adrenergic (hormonal) blockage 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 α-adrenergic blocker phentolamine, the β-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.
Interventions:
description: Physiologic receptor blockade (α1-receptor).
name: Phentolamine
other_name: Regitine
type: Drug
description: Physiologic receptor blockade (β2-receptor).
name: Propranolol
other_name: Inderal
type: Drug
description: 100mL bag of Normal Saline Solution (NSS).
name: Placebo
other_name: Saline
Sodium Chloride Solution
type: Drug
Study arms:
design_group_description: The dose of propranolol will be 0.48 μg/kilogram•minute, which will provide a total dose of 0.10 mg/kg. It will be administered 1 x only via intravenous infusion over 3.5 hours, starting 30 min before conduct of a hyperinsulinemic euglycemic (90 min) followed by hypoglycemia (90 min) clamp.
design_group_title: Group 1-Propranolol Intra-hepatic islet
design_group_type: Active Comparator
design_group_description: The dose of phentolamine will be 0.95 μg/kg•min, which will provide a total dose of 0.20 mg/kg. It will be administered 1 x only via intravenous infusion over 3.5 hours, starting 30 min before conduct of a hyperinsulinemic euglycemic (90 min) followed by hypoglycemia (90 min) clamp.
design_group_title: Group 1-Phentolamine Intra-hepatic islet
design_group_type: Active Comparator
design_group_description: Placebo in 100mL NSS. Infuse Intravenously at 0.0095 ML/KG/MIN. 1 x only via intravenous infusion over 3.5 hours, starting 30 min before conduct of a hyperinsulinemic euglycemic (90 min) followed by hypoglycemia (90 min) clamp.
design_group_title: Group 1- Placebo Intra-hepatic islet
design_group_type: Placebo Comparator
design_group_description: Hyperinsulinemic euglycemic (90 min) followed by hypoglycemia (90 min) clamp only.
design_group_title: Group 2 - Extra-hepatic islet
design_group_type: No Intervention
design_group_description: Hyperinsulinemic euglycemic (90 min) followed by hypoglycemia (90 min) clamp only.
design_group_title: Group 3 - Intra-hepatic auto islet
design_group_type: No Intervention
Sponsor: University of Pennsylvania
Collaborators: National Institute of Diabetes & Digestive & Kidney Diseases
National Institutes of Health
Drug name mappings:
name: 甲磺酸酚妥拉明
lang: CN
name: Phentolamine Mesylate
lang: EN
name: フェントラミンメシル酸塩
lang: JP
name: 盐酸普萘洛尔
lang: CN
name: Propranolol Hydrochloride
lang: EN
name: プロプラノロール塩酸塩
lang: JP