Impact of Dopamine Infusion on Insulin Secretion in Healthy Subjects
Condition: Hyperglycemia; Sepsis
MeSH terms: Hyperglycemia
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

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.
    

Intervention name(s): Dopamine
Intervention type(s): Drug
Intervention description(s): 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.
Intervention MeSH terms: Dopamine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Dopamine; hyperglycemic clamp; sepsis; hyperglycemia; insulin secretion