Natriuretic Peptides and Metabolic Risk in Obesity

Early Phase 1

Withdrawn

• Conditions: Obesity; Hyperinsulinemia
• Interventions: Other: Saline; Drug: Insulin; Drug: Nesiritide

• Registration Number: NCT02642523
• Lead Sponsor: Vanderbilt University Medical Center

Brief Summary

The investigators are examining:

1. the relationships of insulin levels and natriuretic peptide hormone levels, and

2. the effects of administering an infusion of natriuretic peptide hormone on the breakdown of fat

in healthy lean and otherwise healthy obese individuals.

Detailed Description

The cardiac natriuretic peptide hormonal system may protect against the development of cardiometabolic risk. Epidemiologic studies have shown that in relatively healthy individuals without heart failure, low natriuretic peptide levels are associated with unfavorable cardiometabolic phenotypes, including higher blood pressure, obesity, higher insulin levels, and diabetes mellitus. Understanding the mechanisms behind the "natriuretic peptide deficiency" of obesity would illuminate an important way in which obesity interacts with the cardiovascular system.

The investigators propose a prospective cross-over design in 40 healthy lean and otherwise healthy obese individuals. The investigators propose the following specific aims and hypotheses:

Aim 1: To study the effect of hyperinsulinemia on the response of the natriuretic peptide system to salt loading.

Hypothesis 1: Hyperinsulinemia will suppress natriuretic peptide levels in both obese and lean individuals.

Aim 2: To examine the effect of an intravenous infusion of natriuretic peptide on acute markers of lipolysis.

Hypothesis 2: An intravenous infusion of natriuretic peptide will raise acute markers of lipolysis in both obese and lean individuals.

Study Timeline

• Study First Submitted: 2015-11-24
• Study First Submitted QC: 2015-12-24
• Study First Posted: 2015-12-30
• Primary Completion: 2017-02
• Study Completion: 2017-02
• Status Verified: 2017-10
• Last Update Submitted: 2017-10-31
• Last Update Posted: 2017-11-06

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Men and women ages 18-50 years
• BMI 18 to <25 kg/m2 (lean group, N=20) or BMI 30 to <40 kg/m2 (obese group, N=20)

Exclusion Criteria

• Current use of antihypertensive medications
• Current use of glucocorticoids, metformin, or any antidiabetes medications
• Prior or current cardiovascular disease, renal disease, or liver disease
• Diabetes mellitus (taking insulin, other anti-diabetic agents, or diet-controlled)
• Atrial fibrillation
• Bleeding disorder or anemia
• Elevated LFTs
• estimuated GFR < 60 ml/min
• Abnormal sodium or potassium level
• Positive pregnancy test, women of child-bearing age not practicing birth control, women who are breastfeeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Saline Infusion	Saline	All subjects will undergo 3 interventions, performed at 3 separate outpatient study visits. The order of the 3 interventions will be randomly assigned. The interventions are: Saline Infusion, Insulin Clamp, and BNP Infusion (Nesiritide).
Insulin Clamp	Insulin	All subjects will undergo 3 interventions, performed at 3 separate outpatient study visits. The order of the 3 interventions will be randomly assigned. The interventions are: Saline Infusion, Insulin Clamp, and BNP Infusion (Nesiritide).
BNP Infusion (Nesiritide)	Nesiritide	All subjects will undergo 3 interventions, performed at 3 separate outpatient study visits. The order of the 3 interventions will be randomly assigned. The interventions are: Saline Infusion, Insulin Clamp, and BNP Infusion (Nesiritide).

Primary Outcome Measures

Name	Time	Method
Change in glycerol levels	1 hour	Change during 1-hour of low-dose BNP infusion, 1-hour of high-dose BNP infusion, and 1-hour of normal saline infusion
Change in natriuretic peptide levels	4 hours (during 2-hour study infusions and for 2 hours after study infusions)

Secondary Outcome Measures

Name	Time	Method
Change in energy expenditure assessed by indirect calorimetry	1 hour	Change during 1-hour of low-dose BNP infusion, 1-hour of high-dose BNP infusion, and 1-hour of normal saline infusion
Change in triglyceride levels	1 hour	Change during 1-hour of low-dose BNP infusion, 1-hour of high-dose BNP infusion, and 1-hour of normal saline infusion
Change in free fatty acid levels	1 hour	Change during 1-hour of low-dose BNP infusion, 1-hour of high-dose BNP infusion, and 1-hour of normal saline infusion