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Alpha-Adrenergic Blocker

Adrenergic Blockers for Type 1 Diabetes Post-Islet Transplant

Phase < 1

Waitlist Available

Led By Michael R Rickels, MD., MS

Research Sponsored by University of Pennsylvania

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

GROUP 1: Male and female subjects age 21 to 65 years

GROUP 1: Use of standard immunosuppression as specified

Must not have

GROUP 3: Abnormal kidney function: eGFR < 60 ml/min/1.73 m2

GROUP 1: Use of glucocorticoids greater than 5 mg of prednisone daily, or an equivalent physiologic dose of hydrocortisone

Timeline

Screening 3 weeks

Treatment Varies

Follow Up during metabolic testing; this symptom questionnaire will be asked at the following time points: -15min, -1min, 30min, 60min,75min, 90min,120min, 150min, 165min, 180min.

Summary

This trial is looking at whether or not the sympathetic nervous system and hormones have an effect on islet cells in type 1 diabetics who have received intrahepatic islet transplants.

Who is the study for?

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.

What is being tested?

The study tests how blocking different parts of the nervous system affects blood sugar control in those who've received a pancreas cell transplant for diabetes. It involves three drugs: phentolamine (α-adrenergic blocker), propranolol (β-adrenergic blocker), and placebo. Participants will undergo glucose clamps under each condition in a randomized double-blind manner to see if these interventions influence their body's response to low blood sugar.

What are the potential side effects?

Phentolamine may cause low blood pressure, nasal stuffiness or reflex tachycardia; Propranolol can lead to slow heart rate, low blood pressure, fatigue or shortness of breath; Placebo typically has no side effects but mimics treatment experience.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 21 and 65 years old.

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I am using standard immunosuppression medication as directed.

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My insulin needs are low and my blood sugar levels are under control.

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I have had type 1 diabetes since before I was 40, have been on insulin for over 10 years, and had islet transplantation more than 6 months ago.

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My insulin use is low and my blood sugar levels are controlled.

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I am using standard immunosuppressive drugs as directed.

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My insulin needs are low and my blood sugar levels are controlled.

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I am between 21 and 65 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My kidney function is below normal levels.

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I take more than 5 mg of prednisone daily or its equivalent.

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I have a history of heart or blood vessel disease, or I am currently taking β-blocker medication.

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I have bronchial asthma.

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I take more than 5 mg of prednisone daily or its equivalent.

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I use 0.2 units/kg of insulin or more daily.

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My liver tests are more than 1.5 times the normal limit.

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I have seizures not caused by very low blood sugar.

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I use at least 0.2 units per kg of insulin daily.

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I use 0.2 units/kg of insulin or more daily.

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I have active heart or blood vessel disease.

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I have untreated hypothyroidism, Addison's disease, or Celiac disease.

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I have a seizure disorder not caused by very low blood sugar.

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I take more than 5 mg of prednisone daily or its equivalent.

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I am not pregnant, not breastfeeding, and willing to use contraception during the study.

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My hemoglobin is below the normal range for my gender.

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I have a seizure disorder not caused by very low blood sugar.

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I am not pregnant, not breastfeeding, and willing to use contraception during the study.

Select...

I have untreated hypothyroidism, Addison's disease, or Celiac disease.

Select...

My liver tests are more than 1.5 times the normal limit.

Select...

My kidney function is below normal levels.

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I am not pregnant, not breastfeeding, and willing to use contraception during the study.

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My hemoglobin is below the normal range for my gender.

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I have anemia with a hemoglobin level below the normal range for my gender.

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My liver tests are more than 1.5 times the normal limit.

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My kidney function is below normal levels.

Select...

I have active heart or blood vessel disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ during metabolic testing; this symptom questionnaire will be asked at the following time points: -15min, -1min, 30min, 60min,75min, 90min,120min, 150min, 165min, 180min.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~during metabolic testing; this symptom questionnaire will be asked at the following time points: -15min, -1min, 30min, 60min,75min, 90min,120min, 150min, 165min, 180min.

This trial's timeline: 3 weeks for screening, Varies for treatment, and during metabolic testing; this symptom questionnaire will be asked at the following time points: -15min, -1min, 30min, 60min,75min, 90min,120min, 150min, 165min, 180min. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

C-PEPTIDE suppression during hyperinsulinemia euglycemia.

Glucagon

Secondary study objectives

AUTONOMIC SYMPTOMS during hyperinsulinemia

EPINEPHRINE during hyperinsulinemia hypoglycemia.

Rates of ENDOGENOUS GLUCOSE PRODUCTION during hyperinsulinemia hypoglycemia.

Trial Design

5Treatment groups

Active Control

Placebo Group

Group I: Group 1-Propranolol Intra-hepatic isletActive Control1 Intervention

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.

Group II: Group 2 - Extra-hepatic isletActive Control1 Intervention

Hyperinsulinemic euglycemic (90 min) followed by hypoglycemia (90 min) clamp only.

Group III: Group 3 - Intra-hepatic auto isletActive Control1 Intervention

Hyperinsulinemic euglycemic (90 min) followed by hypoglycemia (90 min) clamp only.

Group IV: Group 1-Phentolamine Intra-hepatic isletActive Control1 Intervention

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.

Group V: Group 1- Placebo Intra-hepatic isletPlacebo Group1 Intervention

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.

0 / 35Eligibility criteria met