BNP Pharmacodynamics and Effects on Metabolism in Lean and Obese Subjects

NCT01977859 | Completed Phase 1 DMC

• 1 other identifier: TRIMDFH 472930
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to collect data to help researchers better understand the various causes of obesity, which may lead to the development of new obesity treatment options.

Conditions

Obesity; Cardiovascular Disease; Hypertension; Diabetes

Keywords

B-type Natriuretic Peptide; Metabolism; Insulin infusion

Outcome Measures

Primary Outcomes (1)

• Difference in level of B-type Natriuretic Peptide (BNP)

  Blood samples will be obtained at baseline, during the infusion and after the termination of the infusion for measurement of levels of recombinant human BNP (rhBNP) and N-terminal pro-brain natriuretic peptide (NTpro-BNP).

  Days -2, 7, 14

Secondary Outcomes (4)

• Differences in the expression of NPRC

  Day 7

• Determine whether short term infusion of rhBNP increases metabolic rate and/or fat oxidation

  Day 7

• determine whether short term infusion of rhBNP alters gene expression in subcutaneous adipose tissue and skeletal muscle in a pattern consistent with activation of thermogenic pathways

  Day 7

• Difference in responses of lean and obese subjects

  Days -2, 7, 14

Study Arms (5)

Saline

PLACEBO COMPARATOR

Saline infusion

Drug: Saline

Nesiritide 1.0

ACTIVE COMPARATOR

Nesiritide infused for 90 minute, initially at 0.5 pmol/kg/min and doubled every 15 minutes to achieve a target infusion rate of 1.0 pmol/kg/min, followed by a steady state infusion at the target rate for an additional 150 minutes (4 hours total).

Drug: Nesiritide

Nesiritide 2.0

ACTIVE COMPARATOR

Nesiritide infused for 90 minute, initially at 0.5 pmol/kg/min and doubled every 15 minutes to achieve a target infusion rate of 2.0 pmol/kg/min, followed by a steady state infusion at the target rate for an additional 150 minutes (4 hours total).

Drug: Nesiritide

Nesiritide 4.0

ACTIVE COMPARATOR

Nesiritide infused for 90 minute, initially at 0.5 pmol/kg/min and doubled every 15 minutes to achieve a target infusion rate of 4.0 pmol/kg/min, followed by a steady state infusion at the target rate for an additional 150 minutes (4 hours total).

Drug: Nesiritide

Nesiritide 8.0

ACTIVE COMPARATOR

Nesiritide infused for 90 minute, initially at 0.5 pmol/kg/min and doubled every 15 minutes to achieve a target infusion rate of 8.0 pmol/kg/min, followed by a steady state infusion at the target rate for an additional 150 minutes (4 hours total).

Drug: Nesiritide

Interventions

Nesiritide DRUG

Nesiritide 1.0; Nesiritide 2.0; Nesiritide 4.0; Nesiritide 8.0

Saline DRUG

Saline

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65 years, inclusive
• Men and women
• Able to provide written, informed consent
• Weight stable (± 3 kg) during the 3 months prior to enrollment
• BMI ≤ 25 kg/m2 for lean subjects or ≥ 30 kg/m2 for obese subjects

You may not qualify if:

• \) Diagnosed with any of the following co-morbidities: a) coronary artery disease, angina or heart failure, b) diabetes, c) bleeding disorders, d) infections, e) hepatitis and/or cirrhosis, f) severe asthma or Chronic obstructive pulmonary disease (COPD), g) renal insufficiency, h) bariatric surgery, i) inflammatory bowel disease or malabsorption, j) cancer within the last 3 years (except non-melanoma skin cancer or treated cervical carcinoma in situ), k) psychiatric or eating disorders, l) untreated or inadequately controlled thyroid or other endocrine disorders, m) active rheumatoid arthritis or other inflammatory rheumatic disorder
• Pregnant or nursing women
• Presence of clinically significant abnormalities on electrocardiogram;
• Smoking
• Known hypersensitivity to nesiritide or any of its excipients
• Poor intravenous access
• Use of medications: a) nitrates, b) beta-blockers, c) digoxin, d) anti-diabetic agents, e) oral, injected or chronic topical steroids (inhaled steroids for mild asthma are acceptable), f) chronic use of aspirin or other non-steroidal anti-inflammatory drugs, including COX-2 inhibitors, g) other drugs known to affect immune or metabolic function and h) orlistat, phentermine or other weight loss or anorectic agents.
• Your blood pressure at your screening visit is less than or equal to 100/60 or greater than or equal to 160/100.

Sponsors & Collaborators

• AdventHealth Translational Research Institute: lead
• Sanford-Burnham Medical Research Institute: collaborator

Study Sites (1)

Translational Research Institute for Metabolism and Diabetes

Orlando, Florida, 32804, United States

Location

Related Publications (18)

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Related Links

• Translational Research Institute for Metabolism and Diabetes

MeSH Terms

Conditions

Obesity; Cardiovascular Diseases; Hypertension; Diabetes Mellitus

Interventions

Natriuretic Peptide, Brain; Sodium Chloride

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System 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; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Richard E. Pratley, MD

  AdventHealth

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2013
• First Posted: November 7, 2013
• Study Start: November 1, 2013
• Primary Completion: February 15, 2016
• Study Completion: February 28, 2017
• Last Updated: February 14, 2018

Record last verified: 2018-02

Locations

US (1)