Hypoglycemia Associated Autonomic Failure in Type 1 Diabetes Mellitus (DM)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 by University of Maryland
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Stephen N. Davis, University of Maryland
ClinicalTrials.gov Identifier:
First received: August 17, 2012
Last updated: May 24, 2016
Last verified: May 2016
Exercise is a cornerstone of diabetes management. It helps reduce blood pressure, promote weight loss, lower insulin resistance and improve glucose and lipid (triglyceride and HDL-cholesterol) profiles. Unfortunately, the benefits of exercise are often not embraced by diabetic individuals because of the fear of low blood sugar (hypoglycemia). My laboratory has demonstrated that Autonomic nervous system (ANS) counterregulatory failure plays an important role in exercise associated hypoglycemia in Type 1 DM. ANS responses are significantly reduced in Type 1 DM and are further blunted by antecedent episodes of hypoglycemia. Furthermore, there is a large sexual dimorphism of reduced ANS responses during submaximal exercise in both Type 1 DM and healthy individuals that is unexplained. Accumulating data are demonstrating that serotonergic pathways can regulate ANS discharge. Generally, serotonergic pathways are inhibitory but both single and longer term administration of selective serotonin reuptake inhibitors (SSRI's) such as Prozac has been demonstrated to increase basal epinephrine levels and enhance baroreflex control of Sympathetic nervous system (SNS) activity. What is unknown is whether fluoxetine can also enhance SNS responses and also override the large ANS sexual dimorphism present during sub maximal exercise. Therefore, the purpose of this study is to determine if the SSRI fluoxetine (Prozac) can improve SNS responses during exercise.

Condition Intervention
Type 1 Diabetes
Hypoglycemia Associated Autonomic Failure
Drug: Fluoxetine
Drug: Placebo control

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Hypoglycemia Associated Autonomic Failure in Type 1 DM, SSRI and Exercise

Resource links provided by NLM:

Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • Change in Catecholamines [ Time Frame: During 90 minute experimental period ] [ Designated as safety issue: No ]
    This change in catecholamines will be compared to another 90 minute experimental period after 8 weeks administration of SSRI or placebo.

Estimated Enrollment: 64
Study Start Date: October 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Trial 1-SSRI
90 minute exercise baseline with 6 weeks treatment with SSRI (Prozac). Repeat 90 minute exercise after 6 week treatment.
Drug: Fluoxetine
20 mg week 1, 40 mg week 2, 60 mg week 3, 80 mg week 4-6
Other Name: Prozac
Placebo Comparator: Trial 2-Placebo
90 minute exercise at baseline with 6 weeks treatment with placebo. Repeat 90 minute exercise after 6 weeks treatment of placebo.
Drug: Placebo control
20 mg Week 1, 40 mg Week 2, 60 mg Week 3, 80 mg Week 4-6


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

Inclusion Criteria:

  • 32 (16 males, 16 females) Healthy controls aged 18-45 yr.
  • 32 (16 males, 16 females) Type 1 diabetic patients aged 18-45 yr.
  • HbA1c 6-10.0%
  • Has been diagnosed Type 1 DM
  • No clinically diagnosed diabetic tissue complications (i.e. history of retinopathy, neuropathy, stasis ulcers, etc)
  • Body mass index < 40kg • m-2

Exclusion Criteria:

  • 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
  • Current tobacco use
  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: NCT01672255

Contact: Maka Hedrington, MD 410-706-5623 mhedrington@medicine.umaryland.edu
Contact: Donna Tate 410-706-5642

United States, Maryland
University of Maryland, Baltimore Recruiting
Baltimore, Maryland, United States, 21201
Contact: Donna Tate    410-706-5643      
Principal Investigator: Stephen N. Davis, MBBS         
Sponsors and Collaborators
University of Maryland
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Stephen N. Davis, MBBS University of Maryland
  More Information

Responsible Party: Stephen N. Davis, Principal Investigator, University of Maryland
ClinicalTrials.gov Identifier: NCT01672255     History of Changes
Other Study ID Numbers: SSRI and Exercise 
Study First Received: August 17, 2012
Last Updated: May 24, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by University of Maryland:

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Pure Autonomic Failure
Autoimmune Diseases
Autonomic Nervous System Diseases
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Nervous System Diseases
Primary Dysautonomias

ClinicalTrials.gov processed this record on May 26, 2016