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?

This trial tests how fluoxetine, an antidepressant, and DHEA, a hormone that aids stress management, can assist people with type 1 diabetes in managing low blood sugar. Researchers aim to determine if these treatments, either individually or combined, effectively help the body respond to low blood sugar levels. Candidates for this trial should have type 1 diabetes, controlled blood sugar levels, and no severe diabetes-related complications. As an Early Phase 1 trial, this research focuses on understanding how these treatments work in people, providing an opportunity to contribute to groundbreaking insights.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that fluoxetine, a medication for depression, is generally safe. However, it can sometimes lower blood sugar levels, which is important for people with diabetes to know.

DHEA is a hormone available as a supplement. Research suggests it might affect blood sugar and insulin, crucial for managing diabetes. However, limited information exists on the long-term safety of DHEA, and it can cause side effects like increased levels of certain hormones.

Specific safety information on using fluoxetine and DHEA together is limited. Each has its own safety considerations, and combining them might lead to different effects. This study is in the early stages and aims to learn more about how these treatments interact and their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Fluoxetine and DHEA for treating Type 1 Diabetes because it offers a novel approach compared to traditional insulin therapies. Unlike standard care, which primarily focuses on managing blood sugar levels, this combination may target underlying mechanisms related to stress and hormonal balance. Fluoxetine, typically used for depression, might improve the body's response to insulin by affecting serotonin levels, while DHEA, a hormone, could enhance insulin sensitivity and reduce inflammation. This dual-action approach has the potential to address diabetes management from a new angle, offering hope for more comprehensive control of the condition.

What evidence suggests that this trial's treatments could be effective for type 1 diabetes?

Research has shown that fluoxetine, a common antidepressant, can help control blood sugar in people with diabetes. Studies have found it may also lower fasting blood sugar and help manage diabetes-related health markers. In this trial, some participants will receive fluoxetine alone. In contrast, evidence for DHEA, a hormone supplement, is mixed. Some animal studies suggest it might lower blood sugar, but research in humans indicates it has little effect on glucose levels. Participants in this trial may receive DHEA alone or in combination with fluoxetine. Limited information exists on using fluoxetine and DHEA together, so their combined effect on blood sugar remains unclear. ^{6 7 8 9 10}

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, 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]

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]

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]

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]

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]

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 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]

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Two Years of Treatment With Dehydroepiandrosterone Does ...

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In November 2016, DHEA was approved (as Intrarosa) to treat women experiencing moderate to severe pain during sexual intercourse (dyspareunia), a symptom of ...

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PRASTERA - ® - prasterone oral softgels 200mg are for ...

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Prasterone

Moreover, the long-term safety data for DHEA supplementation is lacking, which is a significant concern. This is particularly relevant given that DHEA ...