Hypoglycemia Associated Autonomic Failure in Type 1 DM

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00592670
Recruitment Status : Completed
First Posted : January 14, 2008
Last Update Posted : December 11, 2014
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Steve Davis, Vanderbilt University

Brief Summary:
It is unclear what effect selective serotonin reuptake inhibitors (SSRIs) have on hypoglycemia. Thus, the American Hospital Formulary Service recommends careful monitoring of blood glucose levels in all patients with diabetes initiating or discontinuing SSRIs (Katz et al., 1996). Because of the increased prevalence of depression in those with diabetes, it is critical to discover what affect the antidepressant therapy may have on counterregulatory responses to hypoglycemia. This study hypothesizes that chronic administration of SSRIs may result in a blunted counterregulatory response to hypoglycemia, thereby leaving individuals more susceptible to hypoglycemia.

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Drug: Fluoxetine Drug: Placebo Not Applicable

Detailed Description:

Because selective serotonin reuptake inhibitors are commonly prescribed to treat depression, it is vital to understand how these antidepressants affect hypoglycemia- the most feared complication in diabetes. This study's aim is to determine whether individuals who are chronically taking selective serotonin reuptake inhibitors have a reduced ability to defend against hypoglycemia compared to individuals not taking the medication, thus leaving them more susceptible to hypoglycemia. Both healthy volunteers and volunteers with type 1 diabetes mellitus will be studied. The results could potentially be important to diabetic patients, by demonstrating to physicians how to modify therapy for those taking antidepressants in order to avoid hypoglycemia.

The known effects of SSRI on the hypothalamo pituitary axis(HPA)may be important to the counterregulation of hypoglycemia. Prior research has demonstrated in healthy volunteers that antecedent increases in plasma cortisol result in significant blunting of neuroendocrine and autonomic responses to subsequent hypoglycemia. Thus, by activating the HPA axis, SSRIs could cause blunting of the counterregulatory response to hypoglycemia.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Official Title: Hypoglycemia Associated Autonomic Failure in Type 1 DM, Question 6
Study Start Date : March 2005
Actual Primary Completion Date : June 2007
Actual Study Completion Date : October 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hypoglycemia
Drug Information available for: Fluoxetine

Arm Intervention/treatment
Experimental: 1
Baseline measures followed by a randomized 6 weeks treatment of Prozac.
Drug: Fluoxetine
20 mg fluoxetine orally one per day for 1 week, 40 mg fluoxetine orally once per day for one week, 80 mg Fluoxetine orally for remaining 4 weeks of treatment
Other Name: Prozac

Placebo Comparator: 2
Baseline followed by a 6 week randomized treatment of placebo.
Drug: Placebo
20 mg placebo pill taken orally once per day for one week, 40 mg placebo pill taken orally one per day for one week, 80 mg placebo pill taken orally once per day for remaining 4 weeks.

Primary Outcome Measures :
  1. Catecholamine measures [ Time Frame: 6 weeks ]

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • 16 (8 males, 8 females) healthy volunteers aged 18-45 yr
  • 34 (17 males, 17 females) type 1 diabetes volunteers aged 18-45 yr
  • Body mass index 21-30 kg • 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
  • Volunteers over 40 years old: normal heart tracing recorded while resting and walking on the treadmill
  • For those with type 1 diabetes: HbA1c > 7.0%
  • For those with type 1 diabetes: had diabetes for 2-15 years
  • For those with type 1 diabetes: no clinical evidence of diabetic tissue complications

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 with any indication of depression, anxiety, bipolar, panic, or eating disorders
  • Subjects with a past medical history or family history of mania or bipolar disorders
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00592670

United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232-0475
Sponsors and Collaborators
Vanderbilt University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: Stephen N. Davis, MD Vanderbilt University

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Steve Davis, Chairman of Medicine.University of Maryland, Vanderbilt University Identifier: NCT00592670     History of Changes
Other Study ID Numbers: IRB#040912-HAAF-T1DM-Q6
First Posted: January 14, 2008    Key Record Dates
Last Update Posted: December 11, 2014
Last Verified: December 2014

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Pure Autonomic Failure
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors