Mechanisms of Hypoglycemia Associated Autonomic Dysfunction Question 2

NCT ID: NCT00574639

Last Updated: 2019-09-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2016-06-30

Brief Summary

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

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.

Conditions

Type 1 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Alprazolam

Intervention Type: DRUG

1 mg given orally prior to morning and afternoon clamps on Day 1

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

1 mg given orally prior to glucose clamps on Day 1 (morning and afternoon)

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.

Group Type: EXPERIMENTAL

Alprazolam

Intervention Type: DRUG

1 mg given orally prior to morning and afternoon clamps on Day 1

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

1 mg given orally prior to glucose clamps on Day 1 (morning and afternoon)

Interventions

Alprazolam

1 mg given orally prior to morning and afternoon clamps on Day 1

Intervention Type: DRUG

Placebo

1 mg given orally prior to glucose clamps on Day 1 (morning and afternoon)

Intervention Type: DRUG

Other Intervention Names

Xanax

Eligibility Criteria

Inclusion Criteria

• 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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Stephen N. Davis, MBBS

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stephen N. Davis, MD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, Baltimore

Locations

University of Maryland, Baltimore

Baltimore, Maryland, United States

Countries

United States

References

Hedrington MS, Tate DB, Younk LM, Davis SN. Effects of Antecedent GABA A Receptor Activation on Counterregulatory Responses to Exercise in Healthy Man. Diabetes. 2015 Sep;64(9):3253-61. doi: 10.2337/db15-0212. Epub 2015 Apr 21.

Reference Type: DERIVED

PMID: 25901095 (View on PubMed)

Other Identifiers

HL056693

Identifier Type: -

Identifier Source: secondary_id

HP-00044868

Identifier Type: -

Identifier Source: org_study_id