Early Phase 1 N=9 Randomized Quadruple-blind Basic Science

Adrenergic System in Islet Transplantation

Type1diabetes · Hypoglycemia · Hypoglycemia Unawareness · Islet Cell Transplantation

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View on ClinicalTrials.gov: NCT03079921 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Apr 2026

Primary outcome: Primary: C-PEPTIDE Suppression During Hyperinsulinemia Euglycemia. — 0.51; 0.56; 0.59 ng/mL

Study Design & Population

Study type: Interventional
Phase: Early Phase 1
Interventions: Phentolamine (Drug); Propranolol (Drug); Placebo (Drug)
Age: Adult, Older Adult · 21+ yrs
Sex: All
Sponsor: University of Pennsylvania
Primary completion: Apr 2019

Outcome Measures

Outcome	Result	p-value
PRIMARY C-PEPTIDE Suppression During Hyperinsulinemia Euglycemia.	0.51; 0.56; 0.59	—
PRIMARY GLUCAGON Activation During Hyperinsulinemia Hypoglycemia.	69.2; 53.0; 58.7	—
SECONDARY EPINEPHRINE During Hyperinsulinemia Hypoglycemia.	900; 456; 362	—
SECONDARY Rates of ENDOGENOUS GLUCOSE PRODUCTION During Hyperinsulinemia Hypoglycemia.	1.23; 1.29; 1.26	—
SECONDARY AUTONOMIC SYMPTOMS During Hyperinsulinemia Hypoglycemia	7.5; 12.4; 10.3	—

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.

Eligibility Criteria

Inclusion Criteria

GROUP 1

Male and female subjects age 21 to 65 years of age.
Subjects who are able to provide written informed consent and to comply with the procedures of the study protocol.
Clinical history compatible with type 1 diabetes with onset of disease at 10 years at the time of islet transplantation > 6 months before study.
Stable islet graft function defined by C-peptide > 0.5 ng/ml and insulin-independent or insulin-dependent with daily insulin requirement 160 mmHg or diastolic blood pressure > 100 mmHg.
History of cardiovascular disease, including coronary artery, cerebrovascular or peripheral vascular disease, or current use of β-blocker therapy.
Bronchial asthma.
Abnormal kidney function: Estimated glomerular filtration rate (eGFR) 1.5 times the upper limit of normal.
Untreated hypothyroidism, Addison's disease, or Celiac disease.
Anemia: baseline hemoglobin concentration 10 years at the time of islet transplantation > 6 months before study.
Stable islet graft function defined by C-peptide > 0.5 ng/ml and insulin-independent or insulin-dependent with daily insulin requirement 160 mmHg or diastolic blood pressure > 100 mmHg.
Active cardiovascular disease, including coronary artery, cerebrovascular or peripheral vascular disease.
Abnormal kidney function: eGFR 1.5 times the upper limit of normal.
Untreated hypothyroidism, Addison's disease, or Celiac disease.
Anemia: baseline hemoglobin concentration 6 months before study.
Stable islet graft function defined by C-peptide > 0.5 ng/ml and insulin-independent or insulin-dependent with daily insulin requirement 160 mmHg or diastolic blood pressure > 100 mmHg.
Active cardiovascular disease, including coronary artery, cerebrovascular or peripheral vascular disease.
Abnormal kidney function: eGFR 1.5 times the upper limit of normal.
Anemia: baseline hemoglobin concentration < 11 g/dl in women and < 12 g/dl in men.
Presence of a seizure disorder not related to prior severe hypoglycemia.
Use of glucocorticoids greater than 5 mg of prednisone daily, or an equivalent physiologic dose of hydrocortisone.
For female participants of child-bearing potential: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of study participation. Oral contraceptives, intra-uterine devices, Norplant®, Depo-Provera®, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable.
Treatment with any anti-diabetic medication other than insulin within 4 weeks of enrollment.
Use of any investigational agents within 4 weeks of enrollment.
Any medical condition that, in the opinion of the PI, will interfere with the safe completion of the study

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Data sourced from ClinicalTrials.gov (NCT03079921). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.