Mechanisms of Hypoglycemia Associated Autonomic Dysfunction Question 2

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

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.

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.

Intervention(s) in this Clinical Trial

• Drug: Alprazolam
  • 1 mg given orally prior to morning and afternoon clamps on Day 1
• Drug: Placebo
  • 1 mg given orally prior to glucose clamps on Day 1 (morning and afternoon)

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Arm 1
  • 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.
• Experimental: Arm 2
  • 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.
• Experimental: Arm 3
  • 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.
• Experimental: Arm 4
  • 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.

Primary Measures

• Change in Epinephrine Levels
  • Time Frame: 32 weeks
    Safety Issue?: No

• 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 50 Years

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

Lead Investigator: University of Maryland Other

Overall Clinical Trial Officials and Contacts

Stephen N. Davis, MD Principal Investigator University of Maryland  

Overall Contact: Donna B. Tate, MS 410-706-5642 dtate@medicine.umaryland.edu

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00574639

Study ID Number: HP-00044868

ClinicalTrials.gov Identifier: NCT00574639

Health Authority: United States: Institutional Review Board