Epinephrine for Diabetes

(Epineprhine Trial)

Overseen By Maka Siamashvili, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Maryland, Baltimore

Must not be taking: Anticoagulants

Disqualifiers: Hypertension, Heart disease, Tobacco, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how epinephrine (also known as adrenaline), a hormone that combats low blood sugar, affects blood vessels and inflammation in healthy individuals. Researchers study various doses of epinephrine to determine its impact on the body's balance between clotting and breaking down clots, as well as inflammation that can lead to artery issues. Healthy participants with a body mass index above 21 might be suitable for this study. As an Early Phase 1 trial, this research seeks to understand how epinephrine functions in people, providing participants an opportunity to contribute to foundational medical knowledge.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on anticoagulant drugs.

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

Research shows that epinephrine is generally safe when used in controlled amounts, though it can have some side effects. Studies have found that common side effects include anxiety, headaches, and a fast heartbeat. These effects are usually mild and resolve on their own.

However, more serious risks exist, especially if epinephrine is given in large amounts or to individuals with certain health issues. For example, it can cause heart rhythm problems, particularly in those with heart conditions or those taking certain medications. It can also lead to breathing problems if not monitored properly.

This trial is in a very early stage, meaning the safety information is not yet complete. Early stages primarily focus on understanding how well participants can tolerate the treatment.

Prospective participants should discuss any health concerns with the trial team to understand the possible risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using epinephrine for diabetes because it offers a novel approach to managing blood sugar levels. Unlike standard treatments that primarily focus on insulin regulation, epinephrine works by influencing the body's response to glucose, potentially offering a new way to stabilize blood sugar. This treatment uses varying doses of epinephrine infusion, allowing researchers to explore the optimal level needed to achieve the best results. By targeting the body's natural adrenaline response, this approach could offer quicker and more flexible management of blood sugar spikes.

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

Research has shown that epinephrine plays a crucial role in controlling blood sugar levels. In individuals with diabetes, it raises blood sugar by altering glucose metabolism. This trial will examine different doses of epinephrine, with some participants receiving an infusion of 0.015, 0.03, or 0.06 ug/kg/min. Studies also indicate that epinephrine aids in breaking down fat, particularly in those with type 1 diabetes, by releasing stored fats into the bloodstream. This hormone affects blood pressure differently in healthy individuals compared to those with diabetes. Overall, even small increases in epinephrine can significantly influence glucose processing and handling in the body. ^{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 healthy individuals aged 18-55 with a BMI over 21. Participants should not have any severe illnesses, infections, or heart problems. They must not be pregnant, breastfeeding, using tobacco, or have allergies to study medications. Volunteers need to agree to use contraception and cannot be on anticoagulants.

Inclusion Criteria

People who are healthy and between 18 and 55 years old.

Your body mass index is higher than 21 kg/m2.

Exclusion Criteria

You have a fever higher than 38.0 degrees Celsius.

Your hematocrit level is lower than 32%.

Your white blood cell count is below 3,000 or above 14,000.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo hyperinsulinemic euglycemic glucose clamp with varying doses of epinephrine or saline infusion

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Epinephrine
• Saline infusion

Trial Overview

The trial studies how different doses of epinephrine affect blood vessel function and the balance between clotting and bleeding in healthy people. It aims to understand epinephrine's role in preventing low blood sugar levels in diabetes by comparing it with saline infusions.

How Is the Trial Designed?

Group I: Epinephrine infusion-0.06 ug/kg/min Experimental Treatment 1 Intervention

Hyperinsulinemic euglycemic glucose clamp with epinephrine infusion of 0.06 ug/kg/min

Group II: Epinephrine infusion-0.03 ug/kg/min Experimental Treatment 1 Intervention

Hyperinsulinemic euglycemic glucose clamp with epinephrine infusion of 0.03 ug/kg/min

Group III: Epinephrine infusion-0.015ug/kg/min Experimental Treatment 1 Intervention

Hyperinsulinemic euglycemic glucose clamp with epinephrine infusion of 0.015 ug/kg/min

Group IV: Saline infusion Placebo Group 1 Intervention

Hyperinsulinemic euglycemic glucose clamp with saline infusion

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

Approved in European Union as Epinephrine for:

• Anaphylaxis
• Cardiac arrest
• Severe allergic reactions

Approved in United States as Epinephrine for:

• Anaphylaxis
• Cardiac arrest
• Severe allergic reactions

Approved in Canada as Epinephrine for:

• Anaphylaxis
• Cardiac arrest
• Severe allergic reactions

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Vanderbilt University

Collaborator

Trials

714

Recruited

6,143,000+

Published Research Related to This Trial

In a study involving nine patients with Type 1 diabetes, a short-term infusion of adrenaline significantly decreased the need for intravenous glucose during the first two hours, indicating a temporary effect on insulin resistance.

The infusion of adrenaline led to a rise in blood glucose levels during a subsequent insulin-glucose test, demonstrating a diabetogenic effect that lasted for about six hours after stopping the adrenaline infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transient insulin resistance following infusion of adrenaline in type 1 (insulin-dependent) diabetes mellitus. Kollind, M., Adamson, U., Lins, PE., et al.[2019]

In a study of 215 patients with insulin-dependent diabetes, the use of alpha-adrenoblockers led to a reduction in blood sugar levels without needing to increase insulin doses, suggesting they can help manage diabetes more effectively.

In contrast, beta-adrenoblockers worsened diabetes control and did not change growth hormone levels, indicating they are not recommended for patients with diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of alpha and beta receptor blockaders on the degree of glycemia, growth hormone content of blood and catecholamine excretion in insulin-dependent diabetes mellitus]. Alekseeva, GG., Iukhlova, NA.[2016]

Epinephrine causes a rapid increase in blood glucose levels by boosting liver glucose production and inhibiting insulin's ability to help cells take up glucose, which can lead to sustained hyperglycemia, especially in individuals with diabetes.

The study highlights that even mild increases in epinephrine during glucose feeding can lead to significant glucose intolerance, indicating that epinephrine plays a crucial role in stress-induced hyperglycemia and affects glucose regulation in diabetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of epinephrine on glucose metabolism in humans: contribution of the liver. Sherwin, RS., Saccà, L.[2017]

During adrenaline infusion, both normotensive (NT) and hypertensive (HT) individuals experienced significant increases in arterial noradrenaline levels, indicating a similar physiological response to stress in both groups.

Adrenaline infusion led to notable decreases in plasma potassium and increases in plasma glucose, with HT individuals showing more pronounced changes, suggesting that hypertension may affect the body's response to stress and glucose regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potassium, glucose, insulin interrelationships during adrenaline infusion in normotensive and hypertensive humans. Gordon, RD., Bachmann, AW., Ballantine, DM., et al.[2019]

In a study of 16 type I diabetic male patients, urinary adrenaline levels were significantly higher compared to 11 matched control subjects, indicating adrenal medulla hyperactivity in diabetics without complications.

Despite the increased adrenaline, noradrenaline levels remained similar between the two groups, suggesting that the heightened adrenaline response may influence insulin requirements and metabolic processes like lipolysis and glycogenolysis in type I diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High urinary excretion of adrenaline in insulin dependent diabetic subjects. Del Rio, G., Marrama, P., Della Casa, L.[2013]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38427076/

Metabolic effect of adrenaline infusion in people with type 1 ...

Individuals with type 1 diabetes respond with increased lipolysis to adrenaline compared with healthy participants by mobilising the abundant NEFAs in plasma.

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/7001181/

Epinephrine and the regulation of glucose metabolism - PubMed

In diabetes, the hyperglycemic effect of epinephrine is markedly accentuated. The enhanced rise in plasma glucose is due to an alternation in response of the ...

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sciencedirect.com

sciencedirect.com/science/article/pii/0735675794902348

Outcome of insulin-treated diabetics receiving epinephrine ...

In DM treated with standard-dose epinephrine (SDE), there were trends toward improved ROSC, BP, EDA, and HA compared with ND. DC was not different. With high- ...

4.

journals.physiology.org

journals.physiology.org/doi/abs/10.1152/ajpendo.00310.2004

Differing physiological effects of epinephrine in type 1 ...

Increases in systolic blood pressure were greater in healthy subjects, but reductions of diastolic blood pressure were greater in T1DM patients with Epi.

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diabetesjournals.org

diabetesjournals.org/diabetes/article/42/2/307/9963/Effects-of-Epinephrine-on-Insulin-Secretion-and

Effects of Epinephrine on Insulin Secretion and Action in ...

We conclude that small increases of plasma EPI can significantly affect determinants of glucose tolerance in both young and old people.

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americanregent.com

americanregent.com/media/3349/epinephrine_sds_12dec2022.pdf

Epinephrine Injection, USP

Safety Data Sheet. According To Federal Register / Vol. 77, No. 58 ... Workers with cardiovascular and pulmonary disorders, hypertension, diabetes ...

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mayoclinic.org/drugs-supplements/epinephrine-injection-route/description/drg-20072429

Epinephrine (injection route) - Side effects & dosage

However, safety and efficacy have not been established in children weighing less than 15 kilograms (kg) using Symjepi™, in children weighing ...

8.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2021/205029s006lbl.pdf

epinephrine injection usp - accessdata.fda.gov

When Epinephrine Injection is administered intravenously, there is risk of pulmonary edema because of the peripheral constriction and cardiac stimulation ...

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go.drugbank.com

go.drugbank.com/drugs/DB00668

Epinephrine: Uses, Interactions, Mechanism of Action

Common and generalized adverse effects: Transient and minor side effects of anxiety, headache, fear, and palpitations may occur with therapeutic doses of ...

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medsafe.govt.nz

medsafe.govt.nz/profs/datasheet/e/EpiPeninj.pdf

Data Sheet – EpiPen – 7-Apr-2025

The risk of cardiac arrhythmias is higher when adrenaline is given to patients receiving digoxin or quinidine. General anaesthetics. Halothane and other ...