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

32 Participants Needed

Trial Summary

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.

How does the drug epinephrine differ from other diabetes treatments?

Epinephrine (adrenaline) is unique in diabetes treatment because it can increase blood sugar levels by stimulating the liver to produce more glucose and inhibiting insulin's ability to lower blood sugar. This contrasts with typical diabetes treatments that aim to lower blood sugar levels. ^{1 2 3 4 5}

What is the purpose of this trial?

Epinephrine is the principal physiologic defense against hypoglycemia in type 1 and longer duration type 2 DM. Despite this, it is unknown how epinephrine regulates in-vivo endothelial function and atherothrombotic balance in humans. The specific aim of our study will be to determine the dose response effects of the key ANS counterregulatory hormone epinephrine on endothelial function, fibrinolytic balance and pro-atherogenic inflammatory mechanisms in healthy humans.

Research Team

Stephen N. Davis, MBBS

Principal Investigator

University of Maryland, Baltimore

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

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

Effect of epinephrine on glucose metabolism in humans: contribution of the liver. [2017]

2. Australia pubmed.ncbi.nlm.nih.gov

Potassium, glucose, insulin interrelationships during adrenaline infusion in normotensive and hypertensive humans. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

High urinary excretion of adrenaline in insulin dependent diabetic subjects. [2013]

4. Germany pubmed.ncbi.nlm.nih.gov

Transient insulin resistance following infusion of adrenaline in type 1 (insulin-dependent) diabetes mellitus. [2019]

5. Russia (Federation) 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]. [2016]