Clinical trial NCT02642523: Natriuretic Peptides and Metabolic Risk in Obesity
Official title: Natriuretic Peptides and Metabolic Risk in Obesity
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Obesity
Hyperinsulinemia
Keywords: natriuretic peptide
insulin
lipolysis
hormones
metabolism
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2015-12-30
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in natriuretic peptide levels
timeFrame: 4 hours (during 2-hour study infusions and for 2 hours after study infusions)
measure: Change in glycerol levels
timeFrame: 1 hour
Secondary outcomes:
measure: Change in free fatty acid levels
timeFrame: 1 hour
measure: Change in triglyceride levels
timeFrame: 1 hour
measure: Change in energy expenditure assessed by indirect calorimetry
timeFrame: 1 hour
Other outcomes:
measure: Change in plasma renin activity
timeFrame: 4 hours (during 2-hour study infusions and for 2 hours after study infusions)
measure: Change in aldosterone
timeFrame: 4 hours (during 2-hour study infusions and for 2 hours after study infusions)
Locations:
Study officials:
affiliation: Vanderbilt Diabetes/Endocrinology
name: Katherine N Bachmann, MD
role: STUDY_DIRECTOR
affiliation: Vanderbilt Cardiovascular Medicine
name: Thomas J Wang, MD
role: PRINCIPAL_INVESTIGATOR
References: