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WithdrawnNCT00605774Updated Dec 11, 2014

Hypoglycemia Associated Autonomic Failure in Type 1 DM, Q5

An interventional study of epinephrine and epinephrine in Type 1 Diabetes, sponsored by Vanderbilt University. Withdrawn. Open to participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2014-12-11.

Sponsored by Vanderbilt University · Not applicable and Interventional

Phase
Not applicable
Study type
Interventional
Enrollment
0
Allocation
Randomized
Ages
18 Years to 45 Years
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

  • Type 1 Diabetes

Keywords

  • catecholamines
  • diabetes
  • exercise
03

In context

Pure Autonomic Failure

56 studies on the registry are indexed under Pure Autonomic Failure; 11 are open to participants now.

Browse Pure Autonomic Failure studies →

Lead sponsor

Vanderbilt University is the lead sponsor of 508 studies on the registry; 19 are open to participants now.

Of its 7 completed or terminated interventional studies of FDA-regulated products, 5 (71%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 45 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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
05

Study design

Phase
Not applicable
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
0 participants (actual)

Study arms

  • Experimental
    1

    Hyperinsulinemic euglycemic glucose clamps x 2 on Day 1 Hyperinsulinemic euglycemic glucose clamp with epinephrine infusion on Day 2

    Drug: epinephrine

  • Experimental
    2

    Day 1 euglycemic exercise period x 2 Day 2 hyperinsulinemic euglycemic glucose clamp with epinephrine infusion

    Drug: epinephrine

Interventions

  • Drugepinephrine

    Epinephrine 0.06 µg/kg/min infused over two hours during experimental period on Day 2

  • Drugepinephrine

    Epinephrine 0.06 µg/kg/min infusion during hyperinsulinemic euglycemic clamp on day 2

06

What researchers measure

Primary outcomes

  1. catecholamine levels

    Time frame: 2 days

07

Study locations

No study locations are listed for this record.

08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 11, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT00605774
Lead sponsor
Vanderbilt University
Responsible party
Steve Davis (Chairman of Medicine, University of Maryland, Baltimore, Vanderbilt University) — Principal investigator
First posted
Jan 31, 2008
Last update
Dec 11, 2014

Study contacts

Stephen N. Davis, MD
principal investigator · Vanderbilt University

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is withdrawn, as verified in Dec 2014. You cannot join it, but the record below documents what was studied.

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