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

NCT01672255 | Completed Early Phase 1 DMC

• 1 other identifier: HP-00044537; SSRI and Exercise
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

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

Keywords

exercise; diabetes; SSRIs

Outcome Measures

Primary Outcomes (1)

• Change in Catecholamines

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

  During 90 minute experimental period

Study Arms (2)

Trial 1-SSRI

ACTIVE COMPARATOR

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

Drug: Fluoxetine

Trial 2-Placebo

PLACEBO COMPARATOR

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

Drug: Placebo control

Interventions

Fluoxetine DRUG

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

Also known as: Prozac

Trial 1-SSRI

Placebo control DRUG

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

Trial 2-Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• (16 males, 16 females) Healthy controls aged 18-45 yr.
• (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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Maryland, Baltimore

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Motor Activity; Diabetes Mellitus

Interventions

Fluoxetine

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Behavior

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals

Study Officials

• Stephen N. Davis, MBBS

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 17, 2012
• First Posted: August 24, 2012
• Study Start: October 1, 2012
• Primary Completion: May 1, 2025
• Study Completion: May 1, 2025
• Last Updated: October 6, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)