Metabolic Effects of Natriuretic Peptide Hormones

NCT03397966 | Terminated Phase 4 Results DMC FDA Drug

• 2 other identifiers: ENDA-025-17SCX001678
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

Accumulating evidence suggests that the natriuretic peptide (NP) hormonal system has important effects on metabolism. However, more information is needed to better understand the effects of NPs on metabolism in humans. Therefore, the investigators propose a study to determine the effects of b-type natriuretic peptide (BNP) on energy and fat metabolism in humans. The investigators' primary hypothesis is that the administration of BNP will increase energy expenditure in humans. The investigators' secondary hypothesis is that BNP administration will promote changes in gene expression in fat tissue suggestive of fat "beiging" in humans. Interventions that safely increase energy expenditure and promote fat "beiging" represent potential strategies for treating metabolic dysfunction due to obesity.

Conditions

Obesity; Cardiovascular Physiological Phenomena; Metabolism

Keywords

obesity; Cardiovascular Physiological Phenomena; metabolism; Energy Metabolism

Outcome Measures

Primary Outcomes (1)

• Change in Resting Energy Expenditure (EE)

  At each visit (Study Visits 1 and 2), resting energy expenditure (EE) will be determined by indirect calorimetry, using a metabolic cart. Energy expenditure will be measured at baseline (just prior to the infusion) and during the 240-minute intravenous infusion at Study Visits 1 and 2. The primary endpoint will be change in resting energy expenditure, calculated as final resting energy expenditure (at end of 240-minute infusion) adjusted for baseline value.

  At baseline and at end of 240-minute IV infusion (at each study visit). (At Study Visit 1 and 2, EE will be assessed at baseline and at end of 240-minute intravenous infusion. Visits will be separated by at least 14 days.)

Secondary Outcomes (1)

• Adipose Tissue Gene Expression of Uncoupling Protein 1 (UCP1)

  A subcutaneous biopsy will be collected after the end of 240-minute IV infusion, at both Study Visits 1 and 2 (Visits will be separated by at least 14 days.)

Study Arms (2)

BNP, then placebo

EXPERIMENTAL

At Study Visit 1, subjects will receive an IV infusion of recombinant human b-type natriuretic peptide (BNP (1-32), nesiritide) for 240 minutes. After a washout period of at least 2 weeks, subjects then present for Study Visit 2, where they will receive an IV infusion of placebo (control, normal saline) for 240 minutes.

Drug: recombinant human BNP(1-32); Drug: placebo (control, normal saline)

Placebo, then BNP

EXPERIMENTAL

At Study Visit 1, subjects will receive an IV infusion of placebo (control, normal saline) for 240 minutes. After a washout period of at least 2 weeks, subjects then present for Study Visit 2, where they will receive an IV infusion of recombinant human b-type natriuretic peptide (BNP (1-32), nesiritide) for 240 minutes.

Drug: recombinant human BNP(1-32); Drug: placebo (control, normal saline)

Interventions

recombinant human BNP(1-32) DRUG

Subjects will receive an IV infusion of recombinant human BNP(1-32) for 240 minutes at a rate of 10 ng/kg/minute for 240 minutes, preceded by an IV bolus of 100 ng/kg.

Also known as: nesiritide, Natrecor

BNP, then placebo; Placebo, then BNP

placebo (control, normal saline) DRUG

Subjects will receive an IV infusion of placebo (normal saline) at a rate of 10 ng/kg/minute for 240 minutes, preceded by an IV bolus of 100 ng/kg.

BNP, then placebo; Placebo, then BNP

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women ages 18-40 years
• Body Mass Index (BMI): 18.5 BMI\<25 kg/m2 (lean) or BMI \> or = 30 kg/m2 (obese)

You may not qualify if:

• Significant cardiovascular disease (including heart failure and atrial fibrillation)
• Significant pulmonary, liver, or renal disease
• Diabetes Mellitus
• Significant Hypertension
• Hypotension
• Thyroid dysfunction
• Active malignancy
• Current or recent use of glucocorticoids
• Current use of antihypertensive medications, including diuretics
• Current use of medications affecting glucose metabolism, including metformin
• Current use of amphetamines or other medications known to affect energy homeostasis
• Currently pregnant or breastfeeding, or unwilling to avoid becoming pregnant or breastfeeding during study duration
• Significant claustrophobia that would prevent the use of the metabolic cart as part of the study protocol
• Currently abnormal serum or plasma sodium or potassium level
• Known hypersensitivity to recombinant human b-type natriuretic peptide, BNP(1-32) (nesiritide), or phenylephrine

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (2)

Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

Nashville, Tennessee, 37212-2637, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Obesity

Interventions

Natriuretic Peptide, Brain; Saline Solution

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Natriuretic Peptides; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

Sample size is limited due to discontinuation of study drug (recombinant human BNP(1-32), nesiritide, Natrecor) by the drug manufacturer (Scios, LLC) after 5/2019. Results are posted for the 5 participants who were able to complete the study procedures prior to the discontinuation of study drug.

Results Point of Contact

• Title: Alp Ikizler, Catherine McLaughlin Hakim Chair in Vascular Biology, Professor of Medicine
• Organization: Vanderbilt University Medical Center

alp.ikizler@vumc.org

615-343-7592

Study Officials

• Talat A Ikizler, MD

  Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The participant and study investigators will be blinded as to which infusion the participant is receiving at which visit. Also, the individuals analyzing the energy expenditure and fat gene expression will be blinded.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: In this cross-over study, each subject will receive BNP infusion at one visit and placebo (control) at the other visit, in random order. The sequence of the treatments will be randomized. There will be a washout period (at least 14 days) between visits.

Study Record Dates

• First Submitted: December 20, 2017
• First Posted: January 12, 2018
• Study Start: July 1, 2018
• Primary Completion: May 1, 2019
• Study Completion: May 1, 2019
• Last Updated: November 25, 2024
• Results First Posted: December 15, 2023

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Relevant IPA underlying a publication will be available within 6 months after publication date
• Access Criteria: Data requests will be evaluated for appropriateness and relevance.

Locations

US (2)