Hypoglycemia Associated Autonomic Failure in Type 1 DM, Q2

Study Overview
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Brief Summary
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Alprazolam (Xanax) will blunt the body's ability to defend itself from low blood sugar.

Detailed Description
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Due to the fundamental importance of glucose as a cerebral fuel, a complex and redundant counterregulatory response to hypoglycemia exists in man. Some studies have shown that prior activation of GABA(A) receptors may result in blunting of counterregulatory responses during next day hypoglycemia. The Specific Aim is to determine if repeated activation of GABA(A) receptors using Alprazolam will result in blunting of neuroendocrine, ANS and metabolic counterregulatory mechanisms during next day hypoglycemia in T1DM and healthy man.

Official Title
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Hypoglycemia Associated Autonomic Failure in Type 1 DM, Question 2

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Drug: Alprazolam
* Other: control group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 16 (8 males, 8 females) Type 1 diabetes patients aged 18-45 yr. 16 (8 males, 8 females) healthy controls aged 18-45 yr. HbA1c > 7.0% (Type 1 diabetes patients) Had diabetes for 2-15 years (Type 1 diabetes patients) No clinical evidence of diabetic tissue complications (Type 1 diabetes patients) Body mass index 21-30 kg · m-2 Normal bedside autonomic function Normal results of routine blood test to screen for hepatic, renal, and hematological abnormalities Female volunteers of childbearing potential: negative HCG pregnancy test Exclusion Criteria: Prior history of poor health: any current or prior disease condition that alters carbohydrate metabolism and prior cardiac events and/or evidence for cardiac disease Hemoglobin of less than 12 g/dl Abnormal results following screening tests Pregnancy Subjects unable to give voluntary informed consent Subjects with known liver or kidney disease Subjects taking steroids Subjects taking beta blockers Subjects on anticoagulant drugs, anemic, or with known bleeding diseases

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2<br>Hyperinsulinemic glucose clamp with Xanax given orally at beginning of each 2 hour clamp on day 1. | Drug: Alprazolam<br>* 1 mg alprazolam given orally 60 minutes prior to each 2 hour glucose clamp on day 1 (x2)<br>* Other names: Xanax;|
| Experimental: 1<br>Hyperinsulinemic glucose clamp in group with no drug. | Other: control group<br>* control group is two hyperinsulinemic glucose clamps on day 1 with no drug given.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Catecholamine levels |  | Comparative study performed every 6-8 weeks |