The Effects of Fluoxetine and/or DHEA

• ClinicalTrials.gov Identifier: NCT03228732
• Recruitment Status: Recruiting
• First Posted: July 25, 2017
• Last Update Posted: September 28, 2020
• Sponsor: University of Maryland, Baltimore
• Information provided by (Responsible Party): Stephen N. Davis, MBBS, University of Maryland, Baltimore

Study Description

Brief Summary:

(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 or disease	Intervention/treatment	Phase
Type 1 Diabetes Mellitus	Drug: Placebo Oral Tablet; Drug: Fluoxetine; Drug: DHEA; Drug: Fluoxetine and DHEA	Early Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• 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
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: 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
• Actual Study Start Date: December 19, 2017
• Estimated Primary Completion Date: December 10, 2022
• Estimated Study Completion Date: December 10, 2022

Arms and Interventions

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 Name: 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 Name: Prozac, dehydroepiandrosterone

Outcome Measures

Primary Outcome Measures :

1. Change in the level of catecholamines in plasma [ Time Frame: An average of 3 years ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

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

Locations

United States, Maryland

University of Maryland; Recruiting

Baltimore, Maryland, United States, 21201

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

Sponsors and Collaborators

University of Maryland, Baltimore

Investigators

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

More Information

• Responsible Party: Stephen N. Davis, MBBS, Chairman of Medicine, University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT03228732
• Other Study ID Numbers: HP-00075896
• First Posted: July 25, 2017
• Last Update Posted: September 28, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Diabetes Mellitus, Type 1; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Fluoxetine; Dehydroepiandrosterone; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Adjuvants, Immunologic; Immunologic Factors