The Effects of Fluoxetine and/or DHEA

Purpose

(1) To determine how the Selective Serotonin Reuptake Inhibitor (SSRI), fluoxetine (Prozac), an antidepressant often used to treat depression, stimulates the participant's body's ability to defend against low blood sugar (hypoglycemia). (2) To learn how a hormone, dehydroepiandrosterone (DHEA), stimulates the participant's body's ability to defend itself from low blood sugar (hypoglycemia). DHEA is a hormone produced naturally in the human body. However, it can be manufactured and is sold as an over-the-counter dietary supplement. The dose the investigators are giving in this study is higher than the usual recommended dosage taken as a supplement for certain medical conditions. (3) To study combined effects of fluoxetine and DHEA during low blood glucose. In the present study, the investigators will measure the participant's body's responses to hypoglycemia when given fluoxetine or DHEA or fluoxetine and DHEA or a placebo (a pill with no fluoxetine or DHEA). Approximately 64 individuals with type 1 diabetes will take part in this study.

Condition

  • Type 1 Diabetes Mellitus

Eligibility

Eligible Ages
Between 18 Years and 50 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • 64 (32 males, 32 females) T1DM patients aged 18-50 yr.
  • HbA1c < 11.0%
  • No clinically diagnosed diabetic tissue complications (i.e. history of retinopathy, neuropathy, stasis ulcers, etc)
  • Body mass index < 40kg · m-2

Exclusion Criteria

  • Pregnancy
  • 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 or past history of severe depression, mania or psychotic disease
  • Subjects that score greater than 50 on the depression scale
  • Subjects unwillingness or inability to comply with approved contraception measures
  • Abnormal results following screening tests and physical examination that are clinically significant
  • Subjects with a history of severe uncontrolled hypertension (i.e., blood pressure greater than 160/100), heart disease, cerebrovascular incidents
  • Clinically significant cardiac abnormalities (e.g. heart failure, arrhythmias, ischemic tachycardia, S-T segment deviations, etc.) from history or from cardiac stress testing in subjects ≥ 40 years old.
  • Pneumonia
  • Hepatic Failure/Jaundice
  • Creatinine greater than 1.6 mg/dl
  • Acute Cerebrovascular/ Neurological deficit
  • Fever greater than 38 °C

Screening Laboratory Tests Exclusion Criteria

- Hematocrit lower than 32

- WBC lower than 3 thou/ul or greater than 14 thou/ul

- Liver Function Tests: SGOT and SGPT greater than twice upper limit of normal range (i.e. greater than 80 U/L).

- TBil greater than 2 mg/dl

- Alkaline Phosphatase greater than 150U/L

- Positive HIV, Hep B, Hep C

- Hepatic transaminase > 2x normal

Study Design

Phase
Early Phase 1
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Participants will be randomized into 2 groups. Group 1 will consist of a random order of Protocol 1 and Protocol 5. Group 2 will consist of a randomized order of Protocols 2, 3, 4
Primary Purpose
Other
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Placebo Comparator
Placebo 1
Visit 1: Study Day 1: Hyperinsulinemia/ euglycemia clamp in the AM and PM. Study Day 2: Hyperinsulinemia/ hypoglycemia clamp in the AM only. 8-weeks of treatment with placebo Visit 2: same as visit 1
  • Drug: Placebo Oral Tablet
    There will be two 2-day inpatient visits with 8-weeks of treatment with placebo between those visits.
Placebo Comparator
Placebo 2
Visit 1: Study Day 1: Hyperinsulinemia/ hypoglycemia clamp in the AM and PM. Study Day 2: Hyperinsulinemia/ hypoglycemia clamp in the AM only. 8-weeks of treatment with placebo Visit 2: same as visit 1
  • Drug: Placebo Oral Tablet
    There will be two 2-day inpatient visits with 8-weeks of treatment with placebo between those visits.
Active Comparator
Fluoxetine
Visit 1: Study Day 1: Hyperinsulinemia/ hypoglycemia clamp in the AM and PM. Study Day 2: Hyperinsulinemia/ hypoglycemia clamp in the AM only. 8-weeks of treatment with fluoxetine Visit 2: same as visit 1
  • Drug: Fluoxetine
    There will be two 2-day inpatient visits with 8-weeks of treatment with fluoxetine between those visits.
  • Drug: Fluoxetine and DHEA
    There will be two 2-day inpatient visits with 8-weeks of treatment with fluoxetine and DHEA between those visits.
    Other names:
    • Prozac, dehydroepiandrosterone
Active Comparator
DHEA
Visit 1: Study Day 1: Hyperinsulinemia/ hypoglycemia clamp in the AM and PM. Study Day 2: Hyperinsulinemia/ hypoglycemia clamp in the AM only. 8-weeks of treatment with DHEA Visit 2: same as visit 1
  • Drug: DHEA
    There will be two 2-day inpatient visits with 8-weeks of treatment with DHEA between those visits.
    Other names:
    • dehydroepiandrosterone
  • Drug: Fluoxetine and DHEA
    There will be two 2-day inpatient visits with 8-weeks of treatment with fluoxetine and DHEA between those visits.
    Other names:
    • Prozac, dehydroepiandrosterone
Active Comparator
Fluoxetine and DHEA
Visit 1: Study Day 1: Hyperinsulinemia/ hypoglycemia clamp in the AM and PM. Study Day 2: Hyperinsulinemia/ hypoglycemia clamp in the AM only. 8-weeks of treatment with fluoxetine and DHEA Visit 2: same as visit 1
  • Drug: Fluoxetine and DHEA
    There will be two 2-day inpatient visits with 8-weeks of treatment with fluoxetine and DHEA between those visits.
    Other names:
    • Prozac, dehydroepiandrosterone

Recruiting Locations

University of Maryland
Baltimore, Maryland 21201
Contact:
Maka S Hedrington, MD
410-706-5623
mhedrington@som.umaryland.edu

More Details

NCT ID
NCT03228732
Status
Recruiting
Sponsor
University of Maryland, Baltimore

Study Contact

Maka S Hedrington, MD
410-706-5623
mhedrington@som.umaryland.edu