Effect of Nesiritide Infusion on Insulin Sensitivity in Healthy Obese Insulin Resistant Subjects

NCT03234751 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: TRIMDFH 1081082
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to compare the effects of nesiritide to placebo administered by a continuous IV infusion over 48 hours for the treatment of insulin resistance in healthy, obese, insulin resistant individuals.

Conditions

Diabetes

Keywords

human B-type natriuretic peptide

Outcome Measures

Primary Outcomes (1)

• IV infusion of nesiritide at a 3pmol/kg rate

  Average changes in glucose disposal rates (GDR) and endogenous glucose production (EGP) from baseline corrected for body weight at steady state of the clamp during the high- and low-dose portions.

  48 hours

Study Arms (2)

Obese nondiabetic insulin resistant subjects- Panel A

ACTIVE COMPARATOR

IV nesiritide 3 pmol/kg/min or placebo for nesiritide

Drug: Continous IV infusion of Nesiritide; Drug: Hyperinsulinemic euglycemic clamp; Drug: Placebo

Obese nondiabetic insulin resistant subjects- Panel B

ACTIVE COMPARATOR

IV nesiritide 2 pmol/kg/min or placebo for nesiritide

Drug: Continous IV infusion of Nesiritide; Drug: Hyperinsulinemic euglycemic clamp; Drug: Placebo

Interventions

Continous IV infusion of Nesiritide DRUG

Nesiritide (fhBNP) administered by continuous IV infusion during 48 hours.

Obese nondiabetic insulin resistant subjects- Panel A; Obese nondiabetic insulin resistant subjects- Panel B

Hyperinsulinemic euglycemic clamp DRUG

48 hours IV infusion of nesiritide on insulin sensitivity (IS) measured by two-step hyperinsulinemic euglycemic clamp in obese nondiabetic insulin resistant subjects.

Obese nondiabetic insulin resistant subjects- Panel A; Obese nondiabetic insulin resistant subjects- Panel B

Placebo DRUG

48 hours of placebo.

Obese nondiabetic insulin resistant subjects- Panel A; Obese nondiabetic insulin resistant subjects- Panel B

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 40-65 years inclusive
• Men and women
• Able to provide written, informed consent
• Weight stable (± 3 kg) during the 3 months prior to enrollment
• BMI ≥ 30 kg/m2; body weight ≤ 106 kg
• Resting blood pressure ≥ 110/60 mmHg and ≤ 150/100 mmHg

You may not qualify if:

• Known coronary artery disease, angina or heart failure
• Type 1 or Type 2 Diabetes (A1c ≥ 6.5% and/or fasting plasma glucose \>125mg/dL)
• Bleeding disorders
• Hemoglobin level \< 12.5 g/dL for women; \< 13.0 g/dL for men
• Acute or chronic infections
• Hepatitis and/or cirrhosis (AST or Alanine Aminotransferase 2.5 times upper limit of normal)
• Severe asthma or chronic obstructive pulmonary disease
• Renal insufficiency (creatinine \> 1.6 mg/dL)
• Prior bariatric surgery
• Inflammatory bowel disease or malabsorption
• Cancer within the last 3 years (except non-melanoma skin cancer or treated cervical carcinoma in situ)
• Psychiatric or eating disorders
• Untreated or inadequately controlled thyroid (abnormal TSH) or other endocrine disorders
• Active rheumatoid arthritis or other inflammatory rheumatic disorder
• Pregnant or nursing women

Sponsors & Collaborators

• AdventHealth Translational Research Institute: lead

Study Sites (1)

Translational Research Institute for Metabolism and Diabetes

Orlando, Florida, 32804, United States

Location

Related Publications (23)

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MeSH Terms

Conditions

Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Richard Pratley, MD

  Translational Reseach institute for Metabolism and Diabetes

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: This study is prospective randomized, double masked, 2-period cross over design, proof of concept study of the effects of intravenously administered rhBNP (nesiritide) on insulin sensitivity in otherwise healthy obese nondiabetic insulin resistant subjects.

Study Record Dates

• First Submitted: July 18, 2017
• First Posted: July 31, 2017
• Study Start: July 13, 2017
• Primary Completion: September 24, 2018
• Study Completion: February 19, 2020
• Last Updated: March 10, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)