Trial Outcomes & Findings for Adrenergic System in Islet Transplantation (NCT NCT03079921)

NCT ID: NCT03079921

Last Updated: 2026-04-27

Results Overview

The primary outcome measures will be the levels of C-peptide during hyperinsulinemia euglycemia.

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

9 participants

Primary outcome timeframe

For C-peptide at the 60-90 minute time-point during the hyperinsulinemic euglycemic-hypoglycemic clamp.

Results posted on

2026-04-27

Participant Flow

We anticipated enrolling in Group 2 and Group 3 but were unable to enroll any participants for these groups. No participants were enrolled in the "Group 2 - Extra-hepatic Islet" and "Group 3 - Intra-hepatic Auto Islet" Arms.

Participants were assigned to all 3 conditions / clamp interventions in random order. 9 individuals enrolled. 8 completed propranolol condition. 7 completed phentolamine condition and all 9 completed placebo condition.

Participant milestones

Participant milestones
Measure	Group 1- Intra-hepatic Islet The 3 hyperinsulinemic clamps Group 1 will undergo are: 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. Propranolol: Physiologic receptor blockade (β2-receptor). Phentolamine Intra-hepatic islet 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. 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.	Group 2 - Extra-hepatic Islet Hyperinsulinemic euglycemic (90 min) followed by hypoglycemia (90 min) clamp only.	Group 3 - Intra-hepatic Auto Islet Hyperinsulinemic euglycemic (90 min) followed by hypoglycemia (90 min) clamp only.
Group 1-Propranolol Intra-hepatic islet STARTED	9	0	0
Group 1-Propranolol Intra-hepatic islet COMPLETED	7	0	0
Group 1-Propranolol Intra-hepatic islet NOT COMPLETED	2	0	0
Group 1-Phentolamine Intra-hepatic islet STARTED	9	0	0
Group 1-Phentolamine Intra-hepatic islet COMPLETED	8	0	0
Group 1-Phentolamine Intra-hepatic islet NOT COMPLETED	1	0	0
Group 1- Placebo Intra-hepatic islet STARTED	9	0	0
Group 1- Placebo Intra-hepatic islet COMPLETED	9	0	0
Group 1- Placebo Intra-hepatic islet NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Group 1- Intra-hepatic Islet The 3 hyperinsulinemic clamps Group 1 will undergo are: 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. Propranolol: Physiologic receptor blockade (β2-receptor). Phentolamine Intra-hepatic islet 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. 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.	Group 2 - Extra-hepatic Islet Hyperinsulinemic euglycemic (90 min) followed by hypoglycemia (90 min) clamp only.	Group 3 - Intra-hepatic Auto Islet Hyperinsulinemic euglycemic (90 min) followed by hypoglycemia (90 min) clamp only.
Group 1-Propranolol Intra-hepatic islet Physician Decision	2	0	0
Group 1-Phentolamine Intra-hepatic islet Adverse Event	1	0	0

Baseline Characteristics

Adrenergic System in Islet Transplantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1- Intra-hepatic Islet n=9 Participants The 3 hyperinsulinemic clamps Group 1 will undergo are: 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. Propranolol: Physiologic receptor blockade (β2-receptor). Phentolamine Intra-hepatic islet 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. 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.	Group 2 - Extra-hepatic Islet Hyperinsulinemic euglycemic (90 min) followed by hypoglycemia (90 min) clamp only.	Group 3 - Intra-hepatic Auto Islet Hyperinsulinemic euglycemic (90 min) followed by hypoglycemia (90 min) clamp only.	Total n=9 Participants Total of all reporting groups
Age, Continuous	50.6 years STANDARD_DEVIATION 10.5 • n=226 Participants	—	—	50.6 years STANDARD_DEVIATION 10.5 • n=702 Participants
Sex: Female, Male Female	5 Participants n=226 Participants	—	—	5 Participants n=702 Participants
Sex: Female, Male Male	4 Participants n=226 Participants	—	—	4 Participants n=702 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=226 Participants	—	—	0 Participants n=702 Participants
Race (NIH/OMB) Asian	0 Participants n=226 Participants	—	—	0 Participants n=702 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=226 Participants	—	—	0 Participants n=702 Participants
Race (NIH/OMB) Black or African American	0 Participants n=226 Participants	—	—	0 Participants n=702 Participants
Race (NIH/OMB) White	9 Participants n=226 Participants	—	—	9 Participants n=702 Participants
Race (NIH/OMB) More than one race	0 Participants n=226 Participants	—	—	0 Participants n=702 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=226 Participants	—	—	0 Participants n=702 Participants
Region of Enrollment United States	9 participants n=226 Participants	—	—	9 participants n=702 Participants
Diabetes Duration (years)	34.0 years STANDARD_DEVIATION 11.6 • n=226 Participants	—	—	34.0 years STANDARD_DEVIATION 11.6 • n=702 Participants
Transplant Duration (years)	5.89 years STANDARD_DEVIATION 2.04 • n=226 Participants	—	—	5.89 years STANDARD_DEVIATION 2.04 • n=702 Participants
BMI (kg/m²)	24.4 (kg/m²) STANDARD_DEVIATION 2.6 • n=226 Participants	—	—	24.4 (kg/m²) STANDARD_DEVIATION 2.6 • n=702 Participants
HbA1c (%)	5.91 % STANDARD_DEVIATION 0.63 • n=226 Participants	—	—	5.91 % STANDARD_DEVIATION 0.63 • n=702 Participants
C-peptide (ng/mL)	1.21 ng/mL STANDARD_DEVIATION 0.30 • n=226 Participants	—	—	1.21 ng/mL STANDARD_DEVIATION 0.30 • n=702 Participants
Insulin Use (U/kg/day)	0.038 U/kg/day STANDARD_DEVIATION 0.057 • n=226 Participants	—	—	0.038 U/kg/day STANDARD_DEVIATION 0.057 • n=702 Participants

PRIMARY outcome

Timeframe: For C-peptide at the 60-90 minute time-point during the hyperinsulinemic euglycemic-hypoglycemic clamp.

Population: Group 2 and Group 3 were not a part of this Primary Outcome Analysis

The primary outcome measures will be the levels of C-peptide during hyperinsulinemia euglycemia.

Outcome measures

Outcome measures
Measure	Group 1-Propranolol Intra-hepatic Islet n=7 Participants 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. Propranolol: Physiologic receptor blockade (β2-receptor).	Group 1-Phentolamine Intra-hepatic Islet n=8 Participants 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. Phentolamine: Physiologic receptor blockade (α1-receptor).	Group 1- Placebo Intra-hepatic Islet n=9 Participants 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. Placebo: 100mL bag of Normal Saline Solution (NSS).	Group 2 - Extra-hepatic Islet Hyperinsulinemic euglycemic (90 min) followed by hypoglycemia (90 min) clamp only.	Group 3 - Intra-hepatic Auto Islet Hyperinsulinemic euglycemic (90 min) followed by hypoglycemia (90 min) clamp only.
C-PEPTIDE Suppression During Hyperinsulinemia Euglycemia.	0.51 ng/mL Standard Error 0.05	0.56 ng/mL Standard Error 0.10	0.59 ng/mL Standard Error 0.12	—	—

PRIMARY outcome

Timeframe: For Glucagon at the 150-180 minute time-point during the hyperinsulinemic euglycemic-hypoglycemic clamp.

Population: Group 2 and Group 3 were not a part of the Primary Outcome analysis

The primary outcome measures will be the levels of glucagon during hyperinsulinemia hypoglycemia.

Outcome measures

Outcome measures
Measure	Group 1-Propranolol Intra-hepatic Islet n=7 Participants 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. Propranolol: Physiologic receptor blockade (β2-receptor).	Group 1-Phentolamine Intra-hepatic Islet n=8 Participants 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. Phentolamine: Physiologic receptor blockade (α1-receptor).	Group 1- Placebo Intra-hepatic Islet n=9 Participants 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. Placebo: 100mL bag of Normal Saline Solution (NSS).	Group 2 - Extra-hepatic Islet Hyperinsulinemic euglycemic (90 min) followed by hypoglycemia (90 min) clamp only.	Group 3 - Intra-hepatic Auto Islet Hyperinsulinemic euglycemic (90 min) followed by hypoglycemia (90 min) clamp only.
GLUCAGON Activation During Hyperinsulinemia Hypoglycemia.	69.2 pg/mL Standard Error 10.0	53.0 pg/mL Standard Error 4.6	58.7 pg/mL Standard Error 8.2	—	—

SECONDARY outcome

Timeframe: During metabolic testing in the 150-180 minute time-point of the hyperinsulinemic euglycemic-hypoglycemic clamp.

Population: Group 2 and Group 3 were not a part of the Secondary Outcome analysis

Secondary outcome measures will include levels of epinephrine during hyperinsulinemia hypoglycemia.

Outcome measures

Outcome measures
Measure	Group 1-Propranolol Intra-hepatic Islet n=7 Participants 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. Propranolol: Physiologic receptor blockade (β2-receptor).	Group 1-Phentolamine Intra-hepatic Islet n=8 Participants 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. Phentolamine: Physiologic receptor blockade (α1-receptor).	Group 1- Placebo Intra-hepatic Islet n=9 Participants 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. Placebo: 100mL bag of Normal Saline Solution (NSS).	Group 2 - Extra-hepatic Islet Hyperinsulinemic euglycemic (90 min) followed by hypoglycemia (90 min) clamp only.	Group 3 - Intra-hepatic Auto Islet Hyperinsulinemic euglycemic (90 min) followed by hypoglycemia (90 min) clamp only.
EPINEPHRINE During Hyperinsulinemia Hypoglycemia.	900 pg/mL Standard Error 235	456 pg/mL Standard Error 110	362 pg/mL Standard Error 88	—	—

SECONDARY outcome

Timeframe: During metabolic testing in the 150-180 minute time-point of the hyperinsulinemic euglycemic-hypoglycemic clamp.

Population: Group 2 and Group 3 were not a part of the Secondary Outcome analysis

Secondary outcome measures will include rates of endogenous glucose production during hyperinsulinemia hypoglycemia

Outcome measures

Outcome measures
Measure	Group 1-Propranolol Intra-hepatic Islet n=7 Participants 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. Propranolol: Physiologic receptor blockade (β2-receptor).	Group 1-Phentolamine Intra-hepatic Islet n=8 Participants 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. Phentolamine: Physiologic receptor blockade (α1-receptor).	Group 1- Placebo Intra-hepatic Islet n=9 Participants 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. Placebo: 100mL bag of Normal Saline Solution (NSS).	Group 2 - Extra-hepatic Islet Hyperinsulinemic euglycemic (90 min) followed by hypoglycemia (90 min) clamp only.	Group 3 - Intra-hepatic Auto Islet Hyperinsulinemic euglycemic (90 min) followed by hypoglycemia (90 min) clamp only.
Rates of ENDOGENOUS GLUCOSE PRODUCTION During Hyperinsulinemia Hypoglycemia.	1.23 mg/kg/min Standard Error 0.06	1.29 mg/kg/min Standard Error 0.14	1.26 mg/kg/min Standard Error 0.06	—	—

SECONDARY outcome

Timeframe: The autonomic symptom score was calculated as the mean of scores at the two hypoglycemic time points during the clamp (165 and 180 minutes).

Population: Group 2 and Group 3 were not a part of the Secondary Outcome analysis

A questionnaire was administered every 15-30 min during the study to quantitate autonomic symptoms as the sum of scores ranging from 0 (none) to 5 (severe) for each of the following symptoms: anxiety, palpitations, sweating, tremor, hunger, and tingling. (6 symptoms) Total scores range 0 - 30, where higher scores indicate greater autonomic symptoms.