Hypoglycemia Associated Autonomic Failure in Type 1 DM, Q2

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

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

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.

Intervention(s) in this Clinical Trial

• Drug: Alprazolam
  • 1 mg alprazolam given orally 60 minutes prior to each 2 hour glucose clamp on day 1 (x2)
• Other: control group
  • control group is two hyperinsulinemic glucose clamps on day 1 with no drug given.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 2
  • Hyperinsulinemic glucose clamp with Xanax given orally at beginning of each 2 hour clamp on day 1.
• Experimental: 1
  • Hyperinsulinemic glucose clamp in group with no drug.

Primary Measures

• Catecholamine levels
  • Time Frame: Comparative study performed every 6-8 weeks
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 45 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: Vanderbilt University Other

Overall Clinical Trial Officials and Contacts

Stephen N Davis, MD Principal Investigator Vanderbilt University  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00592332

Study ID Number: IRB#040908-HAAF-T1DM-Q2

ClinicalTrials.gov Identifier: NCT00592332

Health Authority: United States: Institutional Review Board