Effect of Naltrexone on Counterregulatory Mechanisms in Hypoglycemia

Study Overview
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Brief Summary
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Insulin treatment often causes the blood glucose levels to fall too low. The body usually responds to low blood glucose levels by releasing hormones which act against the insulin to help correct the low blood glucose levels. However, this hormone response can be altered in people with diabetes. Currently there are no therapeutic agents that can be used to improve the recovery from hypoglycemia (low blood sugar). Naltrexone is a tablet used to help people who are addicted to alcohol or morphine-based drugs to remain drug and alcohol-free but it can also affect the levels of the hormones which are released during hypoglycemia. The aim of this study is to determine whether naltrexone can be used to improve and accelerate the recovery from hypoglycemia in patients with type 1 diabetes.

Official Title
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The Effect of Opiate Blockade With Naltrexone on Counterregulatory Mechanisms in Hypoglycemia

Conditions
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Hypoglycemia

Intervention / Treatment
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* Drug: Naltrexone High Dose
* Drug: Naltrexone Low Dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: type 1 diabetes (well controlled, 2-3 hypoglycemic episodes/wk) age 18-55, BMI 18-35 Exclusion Criteria: pregnancy significant diabetes complications liver disease, cirrhosis cardiac disease neurological disorder autonomic neuropathy kidney disease lactose intolerance

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Naltrexone (higher dose)<br>Naltrexone 100mg tablets were randomly given on 1 of 2 occassions (the other was placebo). The drug was administered 12 hours and 1 hour orally pre-procedure to participants. Placebo was given to the high dose group on 1 of their 2 visits- the order in which placebo was given was randomized by dosage arm. | Drug: Naltrexone High Dose<br>* Naltrexone 100mg for two administrations.<br>|
| Experimental: Naltrexone (lower dose)<br>Naltrexone 50mg tablets were randomly given on 1 of 2 occassions (the other was placebo). The drug was administered 12 hours and 1 hour orally pre-procedure to participants. Placebo was given to the low dose group on 1 of their 2 visits- the order in which placebo was given was randomized by dosage arm. | Drug: Naltrexone Low Dose<br>* Naltrexone 50mg for two administrations.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose (mg/dL) | Glucose was measured in the blood throughout the hyperinsulinemic-hypoglycemic clamp study. | End of study (up to 240 minutes) | 
| Glucose Infusion Rate (mg/kg.Min) | The glucose infusion rate corresponds to the amount of 20% dextrose given during the hyperinsulinemic-hypoglycemic clamp study, necessary to keep blood glucose levels at the target range (50-55 mg/dL). | End of study (up to 240 minutes) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucagon (pg/mL) | Glucagon was measured in the blood throughout the hyperinsulinemic-hypoglycemic clamp study. | End of study (up to 240 minutes) | 
| Cortisol (ug/dL) | Cortisol was measured in the blood throughout the hyperinsulinemic-hypoglycemic clamp study. | End of study (up to 240 minutes) | 
| Epinephrine (pg/mL) | Epinephrine was measured in the blood throughout the hyperinsulinemic-hypoglycemic clamp study. | End of study (up to 240 minutes) | 
| Norepinephrine (pg/mL) | Norepinephrine was measured in the blood throughout the hyperinsulinemic-hypoglycemic clamp study. | End of study (up to 240 minutes) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypoglycemia, Type 1 diabetes