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

Sponsor

University of Maryland, Baltimore (Other)

Overall Status

Recruiting

CT.gov ID

NCT01672255

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Enrollment

Location

Arms

146

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Type 1 Diabetes Hypoglycemia Associated Autonomic Failure	Drug: Fluoxetine Drug: Placebo control	Early Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

64 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Hypoglycemia Associated Autonomic Failure in Type 1 DM, SSRI and Exercise

Study Start Date :

Oct 1, 2012

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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

Arm

Intervention/Treatment

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 Names:

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

Outcome Measures

Primary Outcome Measures

Change in Catecholamines [During 90 minute experimental period]
This change in catecholamines will be compared to another 90 minute experimental period after 8 weeks administration of SSRI or placebo.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

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