Hypoglycemia Associated Autonomic Failure in Type 1 Diabetes Mellitus (DM)
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.
Type 1 Diabetes
Hypoglycemia Associated Autonomic Failure
Drug: Placebo control
|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|
- 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.
|Study Start Date:||October 2012|
|Estimated Study Completion Date:||July 2016|
|Estimated Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
Active Comparator: Trial 1-SSRI
90 minute exercise baseline with 6 weeks treatment with SSRI (Prozac). Repeat 90 minute exercise after 6 week treatment.
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01672255
|Contact: Maka Hedrington, MDfirstname.lastname@example.org|
|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|
|Principal Investigator:||Stephen N. Davis, MBBS||University of Maryland, Baltimore County|