Effect of Formoterol on the Counterregulatory Hormonal Response to Hypoglycemia in Type 1 Diabetes.

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). The aim of this study is to determine whether a formoterol inhaler can be used to improve and accelerate the recovery from hypoglycemia in patients with type 1 diabetes.

Detailed Description
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Note: Below is the original detailed description submitted in 2010. The recruitment for this study was stopped at 7 subjects in each study arm. The study design and outcome measures did not change for this study. See below for further details. Original: 15 subjects with well controlled type 1 diabetes and regular hypoglycemia and 15 healthy volunteers will be recruited for this study. If you agree to participate in this study, you will be asked to participate in a screening at Yale New Haven Hospital. Each study subject will undergo two hypoglycemic clamp studies (a procedure where the blood sugar is closely regulated with intravenous insulin and glucose.) In these hypoglycemic clamp studies, the subject will be given an inhaler. On one visit the inhaler will contain formoterol capsules and on the other visit, the subject will be given 'dummy' capsules. Subjects will be required to be admitted to the HRU the night before the study so that glucose levels can be stabilized and hypoglycemia avoided.

Official Title
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The Effect of the Beta 2 Agonist, Formoterol, on Recovery From Hypoglycemia

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: Formoterol
* Other: Placebo


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 18-50 BMI 18-30 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 |
| --- | --- |
| Active Comparator: Type 1 Diabetics<br>The active group were participants with type 1 diabetes. | Drug: Formoterol<br>* Formoterol inhaler, 12mcg capsules, 4 capsules for one administration<br>* Other names: Foradil Aerolizer;Other: Placebo<br>* Participants in both arms received placebo on 1 of the 2 visits.<br>|
| Other: Healthy Volunteers<br>The control group were participants without diabetes, matched by sex, age and BMI to the active comparator group. | Drug: Formoterol<br>* Formoterol inhaler, 12mcg capsules, 4 capsules for one administration<br>* Other names: Foradil Aerolizer;Other: Placebo<br>* Participants in both arms received placebo on 1 of the 2 visits.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucagon (pg/mL) | Glucagon levels will be measured throughout the study to assess whether there are changes during hypoglycemia with inhaled formoterol. These levels will be checked every 20 minutes during the 120 minute study session. Results are presented at the Basal, Euglycemia (30 minutes) and Hypoglycemia (105-120 minutes) stages. | up to 120 minutes | 
| Epinephrine (pg/mL) | Epinephrine levels will be measured throughout the study to assess whether there are changes during hypoglycemia with inhaled formoterol. These levels will be checked every 20 minutes during the 120 minute study session. Results are presented at the Basal, Euglycemia (30 minutes) and Hypoglycemia (105-120 minutes) stages | up to 120 minutes | 
| Norepinephrine (pg/mL) | Norepinephrine levels will be measured throughout the study to assess whether there are changes during hypoglycemia with inhaled formoterol. These levels will be checked every 20 minutes during the 120 minute study session. Results are presented at the Basal, Euglycemia (30 minutes) and Hypoglycemia (105-120 minutes) stages | up to 120 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Glucose Levels (Average) | Blood glucose levels will be checked every 5 minutes during the 120 minute study session in order to maintain blood glucose levels in the normal and hypoglycemic range. Presented is the average of the collected values. | Up to 120 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 1 diabetes, hypoglycemia, formoterol