Hypoglycemia Associated Autonomic Failure in Type 1 DM

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00592670
First received: January 1, 2008
Last updated: December 18, 2008
Last verified: December 2008
  Purpose

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 Intervention
Type 1 Diabetes
Drug: Fluoxetine
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: Hypoglycemia Associated Autonomic Failure in Type 1 DM, Question 6

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Catecholamine measures [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Enrollment: 48
Study Start Date: March 2005
Study Completion Date: October 2008
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00592670

Locations
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232-0475
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Stephen N. Davis, MD Vanderbilt University
  More Information

No publications provided by Vanderbilt University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Stephen N. Davis, MD, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00592670     History of Changes
Other Study ID Numbers: IRB#040912-HAAF-T1DM-Q6, DK69803
Study First Received: January 1, 2008
Last Updated: December 18, 2008
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Hypoglycemia
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
Fluoxetine
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 16, 2014