Fluoxetine + DHEA for Type 1 Diabetes

Recruiting in Palo Alto (17 mi)

Overseen by Stephen N. Davis, MBBS

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: University of Maryland, Baltimore

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

Disqualifiers: Pregnancy, Severe depression, Heart disease, others

Trial Summary

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.

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 2 3 4 5}

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 6 7 8}

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. ^{2 6 7 8 9}

Research Team

Stephen N. Davis, MBBS

Principal Investigator

University of Maryland, Baltimore

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• DHEA (Hormone)
• Fluoxetine (Selective Serotonin Reuptake Inhibitor)
• Fluoxetine and DHEA (Behavioural Intervention)
• Placebo Oral Tablet (Placebo)

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.

Participant Groups

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Maryland Baltimore, MD

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Patients Recruited

540,000+

References

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

Relationships between age, dehydro-epiandrosterone sulphate and plasma glucose in healthy men. [2019] dehydro-epiandrosterone sulphate (DHEAS) has been reported to ameliorate diabetes mellitus in rats.

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

Effect of dehydroepiandrosterone on glucose uptake in cultured human fibroblasts. [2019] Dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) reportedly have antidiabetic and antiobesity effects. The effect of DHEA on glucose uptake in cultured human fibroblasts was examined. Incubation of cells with supraphysiologic concentrations of DHEA (10(-5) mol/L) for > or = 10 hours enhanced 2-deoxyglucose (2-DG) uptake significantly (P

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] Addition of dehydroepiandrosterone sulphate (DHEAS) to standard pituitary replacement may improve quality of life and glucose metabolism. Conflicting results from the previous work probably relate to differences in populations studied and assessment techniques used. We examined the effects of DHEAS on insulin action and the quality of life in female patients with hypopituitary hypoadrenalism.

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

Therapeutic effects of dehydroepiandrosterone metabolites in diabetes mutant mice (C57BL/KsJ-db/db). [2013] Dehydroepiandrosterone (DHEA) fed at 0.4% in the diet is known to exert strong antihyperglycemic effects in C57BL/KsJ genetically diabetic (db/db) mice. Three of the major metabolic products of DHEA; DHEA sulfate, alpha-hydroxyetiocholanolone (alpha-ET), and beta-hydroxyetiocholanolone (beta-ET) when fed at 0.1% in the diet, and one putative product, 17 beta-estradiol, when fed at 0.005% also prevented the development of severe diabetes while having little effect on the amount of food eaten or the rate of weight gain. When suboptimal doses (5-20 micrograms/week) of estradiol were injected in combination with diets containing either alpha-ET or beta-ET, marked potentiating effect was noted, normalization of the hyperglycemia being produced with as little as 0.025% of beta-ET and 0.05% of alpha-ET. The ability of the etiocholanolones to maintain islet integrity and prevent the development of most diabetes symptoms suggests that these metabolites are not merely inactive end products of steroid metabolism, but are physiological effectors in their own right.

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

[Role of prasterone (dehydroepiandrosterone) in substitution therapy for adrenocortical insufficiency]. [2013] Prasterone (dehydroepiandrosterone; DHEA) is a steroid hormone from the adrenal cortex with weak androgenic properties. It can be converted into stronger acting steroids with both androgenic and oestrogenic properties. DHEA also appears to have an affinity with certain receptors in the brain and can act as a neurosteroid. Patients with primary or secondary adrenocortical insufficiency exhibit a marked decrease in DHEA production and the added value of DHEA replacement in these patients has been investigated in three recently published trials. With a daily dose of 50 mg DHEA, the plasma levels of DHEAS (the sulphate of DHEA) increase to levels within the normal range and beneficial effects have been demonstrated for several psychological parameters such as mood, fatigue, general well-being and sexual function. The androgenic side effects on skin and hair appear to be both moderate and acceptable. For patients with adrenocortical insufficiency who function suboptimally despite adequate replacement therapy with glucocorticosteroids and (if indicated) mineralocorticosteroids, these results would seem to justify treatment with a replacement dose of DHEA.

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] The effect of dehydroepiandrosterone (DHEA) on pancreatic islet function of aged rats, an animal model with impaired glucose-induced insulin secretion, was investigated. The following parameters were examined: morphological analysis of endocrine pancreata by immunohistochemistry; protein levels of insulin receptor, IRS-1, IRS-2, PI 3-kinase, Akt-1, and Akt-2; and static insulin secretion in isolated pancreatic islets. Pancreatic islets from DHEA-treated rats showed an increased beta-cell mass accompanied by increased Akt-1 protein level but reduced IR, IRS-1, and IRS-2 protein levels and enhanced glucose-stimulated insulin secretion. The present results suggest that DHEA may be a promising drug to prevent diabetes during aging.

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

The effect of dehydroepiandrosterone on insulin resistance in patients with impaired glucose tolerance. [2019] Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone-sulfate (DHEA-S) are the most abundant steroid hormones in the body. Recently, DHEA-S has gained interest as an antidepressant substance, with positive effects on autoimmune disease such as lupus and ulcerative colitis, as well as obesity, cancer, cardiovascular disease and diabetes. Its effect on insulin resistance is also assumed to be positive, but has not as yet been confirmed. The present cross-over clinical trial was conducted to evaluate the efficacy of DHEA and placebo on insulin resistance.

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

Therapeutic effects of dehydroepiandrosterone (DHEA) in diabetic mice. [2019] Dehydroepiandrosterone (DHEA), a major adrenal secretory steroid in humans, was therapeutic when fed in a concentration of 0.4% to C57BL/KsJ mice with either non-insulin-dependent or insulin-dependent diabetes. Genetically diabetic (db/db) mice of both sexes develop obesity and a glucose intolerance and hyperglycemia associated with insulin resistance by 2 mo of age, and exhibit beta-cell necrosis and islet atrophy by 4 mo. In contrast, DHEA feeding initiated between 1 and 4 mo of age, while only moderately effective in preventing obesity, did prevent the other pathogenic changes and effected a rapid remission of hyperglycemia, a preservation of beta-cell structure and function, and an increased insulin sensitivity as measured by glucose tolerance tests. DHEA feeding was also therapeutic to normal C57BL/KsJ male mice made diabetic by multiple low doses of streptozotocin (SZ). While DHEA treatments did not block either the direct cytotoxic action of SZ on beta-cells or the development of insulitis, the steroid significantly moderated the severity of the ensuing diabetes (reduced hyperglycemia and water consumption, and increased plasma insulin and numbers of residual, granulated beta-cells.

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] Dehydroepiandrosterone (DHEA) and glucocorticoids are steroid hormones synthesised in the adrenal cortex. Administration of DHEA, its sulphate derivative, DHEAS, and more controversially dexamethasone (DEX), a synthetic glucocorticoid, have beneficial effects in diabetic animals. Cultivating BRIN-BD11 cells for 3 days with either DHEAS (30 muM) or DEX (100 nM), reduced total cell number and reduced cell viability and cellular insulin content. DHEAS-treated cells had poor glucose responsiveness and regulated insulin release, coupled with reduced basal insulin release. In contrast, DEX-treated cells lacked responsiveness to glucose and membrane depolarisation, and both protein kinase A (PKA) and protein kinase C (PKC) secretory pathways were desensitised. Therefore, we conclude that this steroid hormone and synthetic glucocorticoid are not beneficial to pancreatic beta-cells in vitro.