Mechanisms of Hypoglycemia Associated Autonomic Dysfunction Question 2 (Alp Ex)

University of Maryland Baltimore (UMB)

Status and phase: Completed; Early Phase 1

Conditions: Type 1 Diabetes

Treatments: Drug: Alprazolam; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00574639

HL056693

HP-00044868

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 14 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Single Blind

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14 participants in 4 patient groups

Arm 1

Experimental group

Description:

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.

Treatment:

Drug: Alprazolam

Arm 2

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Arm 3

Experimental group

Description:

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.

Treatment:

Drug: Alprazolam

Arm 4

Experimental group

Description:

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.

Treatment:

Drug: Placebo