Mechanisms of Hypoglycemia Associated Autonomic Dysfunction Question 2

Study Overview
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Brief Summary
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The purpose of this study is to determine the way by which Alprazolam (Xanax) an anti-anxiety drug affects specialized molecules in your brain called GABA (A) receptors that alter your body's ability to defend itself from low blood sugar (hypoglycemia). We hypothesize that prior activation of GABA (A) receptors may result in blunting of counterregulatory responses during subsequent hypoglycemia and exercise.

Detailed Description
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The ultimate goal of this project is to identify treatments and approaches that will allow patients with diabetes to enjoy all the benefits of good glycemic control without the damaging limitations of severe hypoglycemia. The specific aim of this study is to determine if gamma aminobutyric acid (GABA A) receptors plays a role in the development of exercise associated autonomic dysfunction in type 1 diabetes and healthy man.

Official Title
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Mechanisms of Hypoglycemia-Associated Autonomic Dysfunction. The Effect of Alprazolam on Exercise Induced Hypoglycemia.

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: Alprazolam
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion 14 Type 1 DM patients (7 male and 7 female) aged 18-50 years HBA1c > 6% BMI<35 kg/m2 14 healthy individuals (7 male and 7 female) aged 18-50 years, BMI matched Exclusion Pregnant women Subjects unable to give voluntary informed consent Subjects on anticoagulant drugs, anemic or with known bleeding diatheses Subjects taking any of the following medications will be excluded: Non-selective Beta Blockers, Sedative-Hypnotics, Anticonvulsants, Antiparkinsonian drugs, Antipsychotics, Antidepressants, Mood stabilizers, CNS Stimulants, Opioids, Hallucinogens Subjects with a recent medical illness Subjects with a history of hypertension, heart disease, cerebrovascular incidents Subjects with known liver or kidney disease Physical Exam Exclusion Criteria History of uncontrolled severe hypertension (i.e., blood pressure greater than 150/95) Clinically significant Cardiac Abnormalities (e.g. Heart Failure, Arrhythmia) Pneumonia Hepatic Failure /Jaundice Renal Failure Acute Cerebrovascular/ Neurological deficit Fever greater than 38.0 C Screening Laboratory blood tests Exclusion Criteria according to protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Day 1 study two hyperinsulinemic (high Insulin dose) euglycemic (normal glucose level) clamps x 2. Day 2 exercise for 90 minutes on recumbent bike. Patient randomized to placebo or Xanax (Alprazolam) drug on Day 1 to receive 1 mg orally prior to each clamp. | Drug: Alprazolam<br>* 1 mg given orally prior to morning and afternoon clamps on Day 1<br>* Other names: Xanax;|
| Experimental: Arm 2<br>Day 1 study two hyperinsulinemic (high Insulin dose) euglycemic (normal glucose level) clamps x 2. Day 2 exercise for 90 minutes on recumbent bike. Patient randomized to placebo or Xanax (Alprazolam) drug on Day 1 to receive 1 mg orally prior to each clamp. | Drug: Placebo<br>* 1 mg given orally prior to glucose clamps on Day 1 (morning and afternoon)<br>|
| Experimental: Arm 3<br>Day 1 study two hyperinsulinemic (high Insulin dose) hypoglycemic (low glucose level) clamps x 2. Day 2 exercise for 90 minutes on recumbent bike. Patient randomized to placebo or Xanax (Alprazolam) drug on Day 1 to receive 1 mg orally prior to each clamp. | Drug: Alprazolam<br>* 1 mg given orally prior to morning and afternoon clamps on Day 1<br>* Other names: Xanax;|
| Experimental: Arm 4<br>Day 1 study two hyperinsulinemic (high Insulin dose) hypoglycemic (low glucose level) clamps x 2. Day 2 exercise for 90 minutes on recumbent bike. Patient randomized to placebo or Xanax (Alprazolam) drug on Day 1 to receive 1 mg orally prior to each clamp. | Drug: Placebo<br>* 1 mg given orally prior to glucose clamps on Day 1 (morning and afternoon)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Epinephrine Levels |  | 32 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 Diabetes, Alprazolam, Exercise