The Effects of Fluoxetine and/or DHEA

The Effects of the Selective Serotonin Reuptake Inhibitor, Fluoxetine and/or DHEA, on Neuroendocrine, Autonomic Nervous System and Metabolic Counterregulatory Responses During Repeated Hypoglycemia in T1DM Individuals

(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.

Study Overview

• Status: Recruiting
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo Oral Tablet; Drug: Fluoxetine; Drug: DHEA; Drug: Fluoxetine and DHEA

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Maka Siamashvili, MD; Phone Number: 410-706-5623; Email: msiamashvili@som.umaryland.edu
• Study Contact Backup: Name: Vanessa Briscoe, PhD; Email: vbriscoe@som.umaryland.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland
      • Contact: Maka Siamashvili, MD; Phone Number: 410-706-5623; Email: msiamashvili@som.umaryland.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.
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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in the level of catecholamines in plasma	An average of 3 years

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Investigators: Principal Investigator: Stephen N Davis, MBBS, University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2017
• Primary Completion (Estimated): February 15, 2025
• Study Completion (Estimated): December 15, 2026

Study Registration Dates

• First Submitted: July 20, 2017
• First Submitted That Met QC Criteria: July 21, 2017
• First Posted (Actual): July 25, 2017

Study Record Updates

• Last Update Posted (Actual): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunologic Factors; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Adjuvants, Immunologic; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Selective Serotonin Reuptake Inhibitors; Dehydroepiandrosterone; Fluoxetine
• Other Study ID Numbers: HP-00075896

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No