Epinephrine for Diabetes
(Epineprhine Trial)
Recruiting in Palo Alto (17 mi)
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: Anticoagulants
Disqualifiers: Hypertension, Heart disease, Tobacco, others
Approved in 3 Jurisdictions
Trial Summary
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.
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?
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.
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Trial 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 (Adrenergic Agonist)
- Saline infusion (Other)
Trial OverviewThe 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
4Treatment groups
Experimental Treatment
Placebo Group
Group I: Epinephrine infusion-0.06 ug/kg/minExperimental Treatment1 Intervention
Hyperinsulinemic euglycemic glucose clamp with epinephrine infusion of 0.06 ug/kg/min
Group II: Epinephrine infusion-0.03 ug/kg/minExperimental Treatment1 Intervention
Hyperinsulinemic euglycemic glucose clamp with epinephrine infusion of 0.03 ug/kg/min
Group III: Epinephrine infusion-0.015ug/kg/minExperimental Treatment1 Intervention
Hyperinsulinemic euglycemic glucose clamp with epinephrine infusion of 0.015 ug/kg/min
Group IV: Saline infusionPlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Maryland, BaltimoreBaltimore, MD
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Who Is Running the Clinical Trial?
University of Maryland, BaltimoreLead Sponsor
Vanderbilt UniversityCollaborator
References
Effect of epinephrine on glucose metabolism in humans: contribution of the liver. [2017]Epinephrine causes a prompt increase in blood glucose concentration in the postabsorptive state. This effect is mediated by a transient increase in hepatic glucose production and an inhibition of glucose disposal by insulin-dependent tissues. Epinephrine augments hepatic glucose production by stimulating glycogenolysis and gluconeogenesis. Although its effect on glycogenolysis rapidly wanes, hyperglycemia continues because the effects of epinephrine on gluconeogenesis and glucose disposal persist. Epinephrine-induced hyperglycemia is markedly accentuated by concomitant elevations of glucagon and cortisol or in patients with diabetes. In both cases, the effect of epinephrine on hepatic glucose production is converted from a transient to a sustained response, thereby accounting for the exaggerated hyperglycemia. During glucose feeding, mild elevations of epinephrine that have little effect on fasting glucose levels cause marked glucose intolerance. This exquisite sensitivity to the diabetogenic effects of epinephrine is accounted for by its capacity to interfere with each of the components of the glucoregulatory response, i.e., stimulation of splanchnic and peripheral glucose uptake and suppression of hepatic glucose production. Our findings suggest that epinephrine is an important contributor to stress-induced hyperglycemia and the susceptibility of diabetics to the adverse metabolic effects of stress.
Potassium, glucose, insulin interrelationships during adrenaline infusion in normotensive and hypertensive humans. [2019]1. Significant increases in arterial noradrenaline (NA) of similar magnitude were seen in normotensive (NT) and hypertensive humans (HT) during adrenaline (ADR) infusion. 2. Significant falls in plasma potassium (K+) were observed in both NT and HT during ADR infusion, even at rates equivalent to minor stress. Levels achieved were significantly lower in HT than in NT. 3. Plasma glucose increased significantly in HT at all ADR infusion rates but only at higher rates of infusion in NT. 4. Basal insulin levels were significantly higher in NT than in HT. After cessation of infusion, insulin increased three-fold in HT and two-fold in NT. 5. Infusion of ADR to produce levels seen during mild to moderate stress resulted in significant increases in plasma NA, falls in plasma K+ and increases in plasma glucose. The expected large insulin response to rising glucose was not seen until after ADR was ceased, confirming the inhibitory effect of ADR on glucose stimulated insulin release.
High urinary excretion of adrenaline in insulin dependent diabetic subjects. [2013]In view of the hyperglycemic and ketogenic actions of catecholamines, studies on the adrenergic pattern in diabetic patients are relevant to the management of diabetes. We have studied urinary adrenaline and noradrenaline excretion in 4-hour collections in 16 type I diabetic male patients without signs of autonomic or peripheral neuropathy and 11 age-weight matched controls. In diabetic patients adrenaline levels were higher than control subjects (26.8 +/- 3.9 vs 10.7 +/- 3.0 nmol/4h; p
Transient insulin resistance following infusion of adrenaline in type 1 (insulin-dependent) diabetes mellitus. [2019]Insulin resistance was assessed after an intravenous infusion of adrenaline (50 ng.kg-1.min-1) or saline (control study) given between 08.00 and 08.30 hours in nine patients with Type 1 (insulin-dependent) diabetes mellitus. The blood glucose level during a somatostatin (100 micrograms/h)-insulin (0.4 mU.kg-1.min-1)-glucose (4.5 mg.kg-1.min-1)-infusion-test performed between 10.30 and 14.30 hours served as an indicator of the total body insulin resistance. Blood glucose was maintained around 7 mmol/l between 08.00 and 10.30 hours by a constant infusion of regular insulin (0.57 mU.kg-1.min-1) and a variable infusion of a 20% glucose solution. The infusion of adrenaline raised plasma adrenaline to 2.7 +/- 0.3 nmol/l (mean +/- SEM) at the end of the infusion; thereafter it returned to its basal level within 30 min. The plasma levels of free insulin, glucagon, cortisol and growth hormone were similar in the adrenaline and the control studies from 08.00 to 14.30 hours. In comparison with the control study the infusion of adrenaline decreased the need for intravenous glucose significantly over the initial 2 h. Furthermore, during the somatostatin-insulin-glucose infusion test the blood glucose rose significantly (p less than 0.05) over the initial 2 h; thereafter no significant differences between the two studies were seen. It is concluded that a short term infusion of adrenaline, resembling the adrenergic hormone response to hypoglycaemia, induces a diabetogenic effect which subsides within 6 h after omission of the adrenaline infusion.
[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]Glycemia, growth hormone level and urinary catecholamine excretion were studied in 182 patients suffering from insulin-dependent diabetes mellitus during insulin therapy alone, and in 33 during treatment with insulin plus alpha- and beta-adrenoblockers. Under the effect of alpha-adrenoblockers glycemia proved to fall in the insulin-dependent patients, without increasing the insulin dose. The STH level diminished in these patients under the effect of alpha-adrenoblockers, even when glycemia persisted at the same level. But beta-adrenoblockers aggravated decompensation and the STH level remained unchanged. alpha and beta-adrenoblockers decreased the urinary adrenaline excretion and elevated noradrenaline, dophamine and DOPA excretion, irrespective of blood glycemia. The authors recommend the use of alpha-adrenoblockers to prevent the necessity of a considerable elevation of insulin doses during compensation in patients with the insulin-resistant form of diabetes mellitus. beta-adrenoblockers are not recommended in diabetes mellitus.