Hypoglycemia Associated Autonomic Failure in Type 1 DM, Q5

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
Steve Davis, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00605774
First received: January 18, 2008
Last updated: December 10, 2014
Last verified: December 2014
  Purpose

When a patient with Type 1 diabetes exercises, he or she is more prone to low blood sugar, or hypoglycemia. It is known that antecedent exercise can blunt defense responses, called counterregulatory responses to subsequent hypoglycemia in Type 1 DM, causing him or her to be vulnerable to another bout of hypoglycemia. Epinephrine is one of the important hormones in the defense of blood glucose during both exercise and hypoglycemia. We will test the hypothesis that antecedent exercise will blunt the metabolic, neuroendocrine and cardiovascular effects of subsequent epinephrine infusion in Type 1 DM.


Condition Intervention
Type 1 Diabetes
Drug: epinephrine

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: Hypoglycemia Associated Autonomic Failure in Type 1 DM, Question 5

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • catecholamine levels [ Time Frame: 2 days ] [ Designated as safety issue: No ]

Enrollment: 0
Arms Assigned Interventions
Experimental: 1
Hyperinsulinemic euglycemic glucose clamps x 2 on Day 1 Hyperinsulinemic euglycemic glucose clamp with epinephrine infusion on Day 2
Drug: epinephrine
Epinephrine 0.06 µg/kg/min infused over two hours during experimental period on Day 2
Experimental: 2
Day 1 euglycemic exercise period x 2 Day 2 hyperinsulinemic euglycemic glucose clamp with epinephrine infusion
Drug: epinephrine
Epinephrine 0.06 µg/kg/min infusion during hyperinsulinemic euglycemic clamp on day 2

Detailed Description:

We have recently performed studies to determine whether the critical metabolic actions of epinephrine are blunted in Type 1 DM. These studies have obvious clinical relevance because strategies aimed at increasing circulating levels of epinephrine will not be effective if the metabolic counterregulatory mechanisms (increased endogenous glucose production (EGP), increased lipolysis and reduced glucose uptake) of the hormone are also blunted. Epinephrine was infused to reach circulating levels of ~ 1000 pg/ml (This level of epinephrine is equivalent to values of the hormone observed during hypoglycemia of 50 mg/dl in healthy males and T1DM men with average glucose control) in groups of either intensively treated (HBA1C < 7.0%), conventionally treated (HBA1C > 9.0%) type 1 DM and age, weight matched healthy controls. In the intensively treated DM group, epinephrine's actions to increase EGP, lipolysis and to restrain glucose uptake were significantly reduced (<60%). The mechanism for our finding needs to be determined. Our hypothesis is that antecedent exercise can cause repetitive activations of Autonomic-adrenomedullary responses that lead to downregulation of β-adrenoreceptor mechanisms. Therefore, the combination of blunted epinephrine effects, increased insulin action and reduced levels of the catecholamine might fully explain the vexing clinical question of post exercise hypoglycemia in Type 1 DM. In this application, we will test the hypothesis that antecedent exercise will blunt the metabolic, neuroendocrine and cardiovascular effects of subsequent epinephrine infusion in Type 1 DM.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 28 (14 males, 14 females) conventionally treated Type 1 diabetic patients with HA1C > 8.5%
  • 28 (14 males, 14 females) intensively treated Type 1 diabetic patients with HA1C < 7%
  • 28 (14 males, 14 females) non-diabetic controls
  • Age 18-45 yr.
  • Had diabetes for 2-15 years if diabetic subject
  • No clinical evidence of diabetic tissue complications, no cardiovascular disease
  • Body mass index 21-27kg · 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 a recent medical illness
  • Subjects with known liver or kidney disease
  • Subjects taking steroids
  • Subjects taking beta blockers
  • Subjects on anticoagulant drugs, anemic, or with known bleeding diseases
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00605774

Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Stephen N. Davis, MD Vanderbilt University
  More Information

No publications provided

Responsible Party: Steve Davis, Chairman of Medicine, University of Maryland, Baltimore, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00605774     History of Changes
Other Study ID Numbers: IRB #040911- HAAF in T1DM, Q5, RO1 DK 069803-03
Study First Received: January 18, 2008
Last Updated: December 10, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
catecholamines
diabetes
exercise

Additional relevant MeSH terms:
Hypoglycemia
Pure Autonomic Failure
Autonomic Nervous System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Nervous System Diseases
Primary Dysautonomias
Epinephrine
Epinephryl borate
Racepinephrine
Adrenergic Agents
Adrenergic Agonists
Adrenergic alpha-Agonists
Adrenergic beta-Agonists
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Mydriatics
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Sympathomimetics
Therapeutic Uses
Vasoconstrictor Agents

ClinicalTrials.gov processed this record on May 21, 2015