Fluoxetine + DHEA for Type 1 Diabetes

Overseen By Maka Siamashvili, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Maryland, Baltimore

Must not be taking: Antidepressants, Antipsychotics, Opioids, others

Disqualifiers: Pregnancy, Severe depression, Heart disease, others

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

(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.

Do I need to stop my current medications for the trial?

The trial requires that you stop taking certain medications, including Non-selective Beta Blockers, Sedative-Hypnotics, Anticonvulsants, Antiparkinsonian drugs, Antipsychotics, Antidepressants, Mood stabilizers, CNS Stimulants, Opioids, and Hallucinogens. If you are on any of these, you would need to stop them to participate.

Is the combination of Fluoxetine and DHEA safe for humans?

Research on DHEA, a hormone in the body, suggests it may have positive effects on diabetes and other conditions, but specific safety data for the combination of Fluoxetine and DHEA in humans is not provided in the available studies. ^{1 2 3 4 5}

How is the drug combination of Fluoxetine and DHEA unique for treating Type 1 Diabetes?

This drug combination is unique because DHEA has shown potential in improving insulin sensitivity and preserving beta-cell function, which are crucial for managing diabetes, while Fluoxetine is primarily known as an antidepressant. The combination may offer a novel approach by addressing both metabolic and psychological aspects of diabetes management. ^{1 2 3 5 6}

What evidence supports the effectiveness of the drug combination of Fluoxetine and DHEA for Type 1 Diabetes?

Research suggests that DHEA, a component of the drug combination, may help improve glucose metabolism and has shown antidiabetic effects in animal studies and certain human cell studies. Additionally, DHEA has been observed to have beneficial effects on insulin action in some studies. ^{1 4 7 8 9}

Who Is on the Research Team?

Stephen N. Davis, MBBS

Principal Investigator

University of Maryland, Baltimore

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-50 with Type 1 Diabetes, without severe diabetic complications or a BMI over 40. Participants should have an HbA1c level below 11.0% and not be on certain medications like antidepressants or beta blockers, among others. They must also not have significant heart issues, uncontrolled hypertension, recent severe illnesses, or psychiatric conditions.

Inclusion Criteria

Your HbA1c level is less than 11.0%.

Your body mass index is less than 40.

I do not have complications from diabetes like eye or nerve problems.

Exclusion Criteria

I have a history of severe mental health issues.

You have important abnormal test results or physical exam findings.

Your creatinine level is higher than 1.6 mg/dl.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either fluoxetine, DHEA, both, or a placebo for 8 weeks. The study involves hyperinsulinemia/euglycemia and hypoglycemia clamps.

8 weeks

2 visits (in-person) per treatment arm

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• DHEA
• Fluoxetine
• Fluoxetine and DHEA
• Placebo Oral Tablet

Trial Overview The study tests how fluoxetine (an antidepressant), DHEA (a hormone supplement), and their combination affect the body's defense against low blood sugar in people with Type 1 Diabetes compared to a placebo. The goal is to understand if these substances can improve hypoglycemia responses.

How Is the Trial Designed?

Group I: Fluoxetine Active Control 1 Intervention

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

Group II: DHEA Active Control 1 Intervention

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

Group III: Fluoxetine and DHEA Active Control 1 Intervention

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

Group IV: Placebo 1 Placebo Group 1 Intervention

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

Group V: Placebo 2 Placebo Group 1 Intervention

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

DHEA is already approved in United States, European Union, Canada for the following indications:

Approved in United States as DHEA for:

• Adrenal insufficiency
• Hypogonadism
• Menopause symptoms
• Anti-aging (off-label)
• Bodybuilding (off-label)

Approved in European Union as Prasterone for:

• Vulvar and vaginal atrophy

Approved in Canada as DHEA for:

• Adrenal insufficiency
• Hypogonadism

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Published Research Related to This Trial

In a study of 169 healthy men with an average age of 46.5 years, serum DHEAS levels were found to significantly decline with age, which is associated with increased fasting plasma glucose levels.

The research suggests that lower DHEAS levels may contribute to the rise in plasma glucose as men age, indicating a potential link between DHEAS and glucose metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationships between age, dehydro-epiandrosterone sulphate and plasma glucose in healthy men. Thomas, N., Morris, HA., Scopacasa, F., et al.[2019]

DHEA significantly enhances glucose uptake in human fibroblasts when used at high concentrations (10^-5 mol/L), indicating its potential role in improving glucose metabolism.

The mechanism involves increasing the expression of glucose transporter-1 (Glut-1) mRNA, suggesting that DHEA may help in managing conditions like diabetes and obesity by promoting glucose uptake in cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of dehydroepiandrosterone on glucose uptake in cultured human fibroblasts. Nakashima, N., Haji, M., Sakai, Y., et al.[2019]

In a study involving 14 hypopituitary females, adding 50 mg of DHEAS daily to standard replacement therapy significantly increased serum DHEAS and androstenedione levels to normal ranges, but did not improve quality of life or insulin action after 12 weeks.

Despite lower triglyceride levels observed with DHEAS treatment, there were no significant changes in fasting glucose, serum insulin, or overall insulin action compared to placebo, suggesting that DHEAS may not be beneficial when added to standard therapy for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of dehydroepiandrosterone sulphate (DHEAS) replacement on insulin action and quality of life in hypopituitary females: a double-blind, placebo-controlled study. McHenry, CM., Bell, PM., Hunter, SJ., et al.[2013]

DHEA and its metabolites, particularly alpha-hydroxyetiocholanolone (alpha-ET) and beta-hydroxyetiocholanolone (beta-ET), effectively prevent severe diabetes in genetically diabetic mice without affecting food intake or weight gain, indicating their potential as safe therapeutic agents.

The study suggests that these metabolites are active physiological effectors that help maintain islet integrity and normalize hyperglycemia, especially when combined with low doses of estradiol, highlighting their efficacy in diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic effects of dehydroepiandrosterone metabolites in diabetes mutant mice (C57BL/KsJ-db/db). Coleman, DL., Leiter, EH., Applezweig, N.[2013]

Prasterone (DHEA) replacement therapy at a daily dose of 50 mg effectively raises plasma DHEAS levels to normal, showing beneficial effects on mood, fatigue, general well-being, and sexual function in patients with adrenocortical insufficiency.

The treatment appears to have moderate and acceptable androgenic side effects on skin and hair, making it a justifiable option for patients who do not fully respond to standard glucocorticosteroid therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Role of prasterone (dehydroepiandrosterone) in substitution therapy for adrenocortical insufficiency]. Zelissen, PM., Thijssen, JH.[2013]

In aged rats, treatment with dehydroepiandrosterone (DHEA) led to an increase in beta-cell mass and improved glucose-stimulated insulin secretion, indicating a potential benefit for pancreatic function.

DHEA treatment was associated with higher levels of Akt-1 protein but lower levels of insulin receptor and insulin signaling proteins, suggesting a complex mechanism of action that may help prevent diabetes as the rats age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dehydroepiandrosterone increases beta-cell mass and improves the glucose-induced insulin secretion by pancreatic islets from aged rats. Medina, MC., Souza, LC., Caperuto, LC., et al.[2018]

In a cross-over clinical trial involving 30 patients with Impaired Glucose Tolerance, DHEA treatment showed a significant increase in DHEA-S levels but did not lead to a reduction in insulin resistance, as measured by HOMA-IR.

While there was a tendency for improvement in insulin resistance with DHEA, the results were not statistically significant, suggesting that DHEA may have a limited effect on insulin resistance in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of dehydroepiandrosterone on insulin resistance in patients with impaired glucose tolerance. Talaei, A., Amini, M., Siavash, M., et al.[2019]

DHEA, when fed to genetically diabetic mice, significantly improved hyperglycemia and preserved beta-cell function, indicating its potential as a therapeutic agent for diabetes.

In normal mice made diabetic through streptozotocin, DHEA treatment did not prevent initial beta-cell damage but effectively reduced the severity of diabetes symptoms, suggesting it may help manage diabetes progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic effects of dehydroepiandrosterone (DHEA) in diabetic mice. Coleman, DL., Leiter, EH., Schwizer, RW.[2019]

Both DHEAS and dexamethasone (DEX) negatively impact pancreatic beta-cell health, reducing cell viability and insulin content in BRIN-BD11 cells after 3 days of treatment.

DHEAS-treated cells showed poor glucose responsiveness, while DEX-treated cells were unresponsive to glucose and membrane depolarization, indicating that neither treatment is beneficial for insulin secretion in vitro.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deleterious effects of supplementation with dehydroepiandrosterone sulphate or dexamethasone on rat insulin-secreting cells under in vitro culture condition. Liu, HK., Green, BD., McClenaghan, NH., et al.[2018]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Relationships between age, dehydro-epiandrosterone sulphate and plasma glucose in healthy men. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Effect of dehydroepiandrosterone on glucose uptake in cultured human fibroblasts. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Effects of dehydroepiandrosterone sulphate (DHEAS) replacement on insulin action and quality of life in hypopituitary females: a double-blind, placebo-controlled study. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

Therapeutic effects of dehydroepiandrosterone metabolites in diabetes mutant mice (C57BL/KsJ-db/db). [2013]

5. Netherlands pubmed.ncbi.nlm.nih.gov

[Role of prasterone (dehydroepiandrosterone) in substitution therapy for adrenocortical insufficiency]. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Dehydroepiandrosterone increases beta-cell mass and improves the glucose-induced insulin secretion by pancreatic islets from aged rats. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

The effect of dehydroepiandrosterone on insulin resistance in patients with impaired glucose tolerance. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Therapeutic effects of dehydroepiandrosterone (DHEA) in diabetic mice. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Deleterious effects of supplementation with dehydroepiandrosterone sulphate or dexamethasone on rat insulin-secreting cells under in vitro culture condition. [2018]