Natriuretic Peptides and Metabolic Risk in Obesity

NCT02642523 | Withdrawn Early Phase 1 DMC

• 1 other identifier: 151768
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The investigators are examining:

1. 1.the relationships of insulin levels and natriuretic peptide hormone levels, and
2. 2.the effects of administering an infusion of natriuretic peptide hormone on the breakdown of fat

Conditions

Obesity; Hyperinsulinemia

Keywords

natriuretic peptide; insulin; lipolysis; hormones; metabolism

Outcome Measures

Primary Outcomes (2)

• Change in natriuretic peptide levels

  4 hours (during 2-hour study infusions and for 2 hours after study infusions)

• Change in glycerol levels

  Change during 1-hour of low-dose BNP infusion, 1-hour of high-dose BNP infusion, and 1-hour of normal saline infusion

  1 hour

Secondary Outcomes (3)

• Change in free fatty acid levels

  1 hour

• Change in triglyceride levels

  1 hour

• Change in energy expenditure assessed by indirect calorimetry

  1 hour

Other Outcomes (2)

• Change in plasma renin activity

  4 hours (during 2-hour study infusions and for 2 hours after study infusions)

• Change in aldosterone

  4 hours (during 2-hour study infusions and for 2 hours after study infusions)

Study Arms (3)

Saline Infusion

PLACEBO COMPARATOR

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).

Other: Saline

Insulin Clamp

EXPERIMENTAL

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).

Drug: Insulin

BNP Infusion (Nesiritide)

EXPERIMENTAL

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).

Drug: Nesiritide

Interventions

Nesiritide DRUG

Subjects will receive an intravenous infusion of recombinant human b-type natriuretic peptide (BNP) (Nesiritide) over 2 hours at 2 doses: 0.003 ug/kg/min for 1 hour, followed by 0.01 ug/kg/min for 1 hour. Nesiritide (Johnson and Johnson) is FDA-approved for the treatment of heart failure. Study investigators received approval from the FDA for an IND exemption for nesiritide in this study. While receiving the BNP infusion, subjects will also receive an intravenous infusion of normal (0.9%) saline over 2 hours. Subjects will receive a standardized high-salt diet for at least 6 days prior to this study visit.

Also known as: Recombinant human BNP

BNP Infusion (Nesiritide)

Insulin DRUG

The hyperinsulinemic-euglycemic insulin clamp, which will last between 2-2.5 hours, involves continuous intravenous infusions of human regular insulin and of dextrose solution. Simultaneously, subjects receive an intravenous infusion of normal (0.9%) saline over 2 hours. Subjects will receive a standardized high-salt diet for at least 6 days prior to this study visit.

Also known as: Human Insulin

Insulin Clamp

Saline OTHER

Subjects will receive an intravenous infusion of normal (0.9%) saline over 2 hours at a rate of 0.25 ml/kg/min. Subjects will receive a standardized high-salt diet for at least 6 days prior to this study visit.

Also known as: Normal Saline

Saline Infusion

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

MeSH Terms

Conditions

Obesity; Hyperinsulinism; Insulin Resistance

Interventions

Natriuretic Peptide, Brain; Insulin; Sodium Chloride; Saline Solution

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Natriuretic Peptides; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins; Proinsulin; Insulins; Pancreatic Hormones; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Katherine N Bachmann, MD

  Vanderbilt Diabetes/Endocrinology

  STUDY DIRECTOR

• Thomas J Wang, MD

  Vanderbilt Cardiovascular Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 24, 2015
• First Posted: December 30, 2015
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2017
• Last Updated: November 6, 2017

Record last verified: 2017-10