Impact of Dopamine Infusion on Insulin Secretion in Healthy Subjects

This is a clinical study of a drug named dopamine and how it affects our bodies ability to make and secrete insulin. Insulin is a hormone made in the pancreas that helps our body regulate sugar levels. We think that this drug decreases the amount of insulin our body makes and causes our sugar levels to be high. When you are critically ill there can be many adverse effects if you have sugar levels that are too high.

Study Overview

• Status: Completed
• Conditions: Hyperglycemia; Sepsis
• Intervention / Treatment: Drug: Dopamine

Detailed Description

Rationale Role of dopamine infusion on pancreatic beta cell function in health and disease remain undetermined in humans. Increasingly, hyperglycemia in the critical care arena bodes poorly on health outcomes.

This study for the first time investigates the role of dopamine infusion in health and has the potential to guide larger studies on impact of dopamine use in critical illness.

Study Design This project will be a prospective, single-center trial to determine the effect of dopamine in healthy subjects using the hyperglycemic clamp.

Study Procedures:

After signing informed consent subjects will undergo screening at the clinical research center after an overnight fast. At this visit, a complete history and physical exam including vital signs, height, weight, BMI, waist circumference will be obtained. Cardiac conditions will be screened using an EKG. Baseline labs will be drawn at this visit, including CBC, chemistry, liver function tests, hemoglobin AIC, thyroid function tests, lipids and cortisol. Females will have a urine beta HCG.

Subjects that meet study criteria will return within 30 days of screening to the clinical research after an overnight fast. One large bore (20 gauge) venous cannula will be inserted in the antecubital fossa for infusion of dopamine and dextrose 20% intravenous solution. Another cannula will be inserted in the contralateral arm for frequent blood sampling.

Insulin sensitivity will be determined using the gold standard hyperglycemic clamp as previously described (DeFronzo, 1979).13 Each subject will act as their own control and receive placebo infusion followed by dopamine infusions.

Subjects will have their blood pressure, heart rate, and glucose monitored every 10 minutes. Each subject will receive a priming dose of dextrose 20% to increase their glucose concentration by 125 mg/dl in the first 15 minutes. Then they will receive variable rates of dextrose 20% infusion to maintain glucose level at 180-220 mg/dl. C-peptide, insulin, glucagon and catecholamine levels will be drawn at 30 min and 60 min to determine baseline levels prior to dopamine infusion. Then, dopamine (200mg/250ml) will be titrated up to 5 mcg/kg/min with care not to increase blood pressure greater than 160 systolic. C-peptide, insulin level, glucagon, plasma catecholamines will be measured at 90 min and 120 min, 150min, 180min, 210min, 240min. At 120min, 180 min and 240 min glucagon and cortisol levels will also be measured. The total amount of blood withdrawn for entire study will be less than 100 ml. After all blood samples are drawn, dextrose and dopamine infusion will be down-titrated and stopped. The subject will be given lunch and glucose level will be checked. Venous cannulas will then be removed and subject will be sent home.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center of Albert Einstein College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy subjects
2. Age 18-35 years
3. Hemoglobin >12 g/dl
4. Euthyroid or on a stable dose of synthroid
5. Normal EKG, hemoglobin AIC, kidney and liver function

Exclusion Criteria:

1. Prior history of dopamine infusion
2. Past medical history of diabetes, hypertension, myocardial infarction, vaso-occlusive disease or arrhythmias
3. Chronic steroid therapy, oral contraceptive pills, monoamine oxidase inhibitors (MAO-I), anticonvulsants (phenytoin)
4. Pregnant women because dopamine is pregnancy category C
5. Clinical signs of polycystic ovarian syndrome
6. Past medical history of Cushing's disease or pheochromocytoma
7. Sulfa drug allergy
8. Use of any medications or illness determined by the investigators that may affect insulin secretion or insulin sensitivity.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

OTHER: Dopamine; All patients will receive the same intervention.

Drug: Dopamine; Each subject will receive a priming dose of dextrose 20% to increase their glucose concentration by 125 mg/dl in the first 15 minutes. Then they will receive variable rates of dextrose 20% infusion to maintain glucose level at 180-220 mg/dl. Then, dopamine (200mg/250ml) will be titrated up to 5 mcg/kg/min with care not to increase blood pressure greater than 160 systolic. Dopamine will be infused for 3 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
insulin secretion	Insulin secretion will be assessed via glucose infusion requirement during a hyperglycemic clamp. Insulin and c-peptide levels will be monitored. Insulin secretion will be attenuated by 30% from baseline in subjects receiving dopamine	4 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
counter-regulatory hormones	Counter-regulatory hormone concentrations before, during and after dopamine infusion	4 hours

Collaborators and Investigators

• Sponsor: Albert Einstein College of Medicine
• Investigators: Study Director: Erika Mark, DO, Albert Einstein College of Medicine

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (ACTUAL): January 1, 2016
• Study Completion (ACTUAL): January 1, 2016

Study Registration Dates

• First Submitted: February 3, 2014
• First Submitted That Met QC Criteria: February 3, 2014
• First Posted (ESTIMATE): February 4, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): August 9, 2016
• Last Update Submitted That Met QC Criteria: August 5, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: sepsis; Dopamine; hyperglycemia; insulin secretion; hyperglycemic clamp
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Cardiotonic Agents; Dopamine Agents; Sympathomimetics; Dopamine
• Other Study ID Numbers: 2013-286