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

NCT ID: NCT01672255

Last Updated: 2025-10-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2025-05-31

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.

Conditions

Type 1 Diabetes; Hypoglycemia Associated Autonomic Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Trial 1-SSRI

90 minute exercise baseline with 6 weeks treatment with SSRI (Prozac). Repeat 90 minute exercise after 6 week treatment.

Group Type: ACTIVE_COMPARATOR

Fluoxetine

Intervention Type: DRUG

20 mg week 1, 40 mg week 2, 60 mg week 3, 80 mg week 4-6

Trial 2-Placebo

90 minute exercise at baseline with 6 weeks treatment with placebo. Repeat 90 minute exercise after 6 weeks treatment of placebo.

Group Type: PLACEBO_COMPARATOR

Placebo control

Intervention Type: DRUG

20 mg Week 1, 40 mg Week 2, 60 mg Week 3, 80 mg Week 4-6

Interventions

Fluoxetine

20 mg week 1, 40 mg week 2, 60 mg week 3, 80 mg week 4-6

Intervention Type: DRUG

Placebo control

20 mg Week 1, 40 mg Week 2, 60 mg Week 3, 80 mg Week 4-6

Intervention Type: DRUG

Other Intervention Names

Prozac

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Stephen N. Davis, MBBS

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stephen N. Davis, MBBS

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, Baltimore

Locations

University of Maryland, Baltimore

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

HP-00044537; SSRI and Exercise

Identifier Type: -

Identifier Source: org_study_id