Adrenergic Blockers for Type 1 Diabetes Post-Islet Transplant
Trial Summary
What is the purpose of this trial?
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.
Will I have to stop taking my current medications?
The trial requires that you do not take any anti-diabetic medication other than insulin within 4 weeks of enrollment. If you are on other medications, you may need to stop them before joining the study.
What evidence supports the effectiveness of the drug propranolol for patients with type 1 diabetes post-islet transplant?
Is propranolol safe for people with Type 1 Diabetes?
How does the drug Phentolamine and Propranolol differ from other treatments for Type 1 Diabetes post-islet transplant?
This drug combination is unique because it involves both alpha and beta-adrenergic blockers, which can influence insulin secretion and glucose tolerance. While propranolol, a beta-blocker, can impair recovery from low blood sugar, phentolamine, an alpha-blocker, may help improve glucose tolerance, offering a novel approach to managing blood sugar levels in patients with transplanted islets.1231011
Research Team
Michael R Rickels, MD., MS
Principal Investigator
Division of Endocrinology, Diabetes & Metabolism, Perelman School of Medicine
Eligibility Criteria
This trial is for adults aged 21-65 with type 1 diabetes who have had an islet cell transplant at least 6 months ago. They should be using standard immunosuppression, have stable graft function, and not require high doses of insulin. Women must not be pregnant or breastfeeding and willing to use contraception. Exclusions include severe chronic diseases, uncontrolled hypertension, obesity (BMI ≥30), abnormal organ functions, certain medication uses within the last month, and other conditions that could affect safety.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants undergo hyperinsulinemic euglycemic-hypoglycemic clamps with administration of α-adrenergic blocker phentolamine, β-adrenergic blocker propranolol, or placebo
Follow-up
Participants are monitored for safety and effectiveness after treatment
Treatment Details
Interventions
- Phentolamine
- Placebo
- Propranolol
Phentolamine is already approved in United States, Canada, European Union for the following indications:
- Hypertension
- Pheochromocytoma
- Hypertension
- Pheochromocytoma
- Hypertension
- Pheochromocytoma
Find a Clinic Near You
Who Is Running the Clinical Trial?
University of Pennsylvania
Lead Sponsor
National Institutes of Health (NIH)
Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborator