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

Phase 1

Completed

• Conditions: Diabetes
• Interventions: Drug: Continous IV infusion of Nesiritide; Drug: Hyperinsulinemic euglycemic clamp; Drug: Placebo

• Registration Number: NCT03234751
• Lead Sponsor: AdventHealth Translational Research Institute

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-07-13
• Study First Submitted: 2017-07-18
• Study First Submitted QC: 2017-07-26
• Study First Posted: 2017-07-31
• Primary Completion: 2018-09-24
• Study Completion: 2020-02-19
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-09
• Last Update Posted: 2020-03-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

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

Exclusion Criteria

1. Known coronary artery disease, angina or heart failure
2. Type 1 or Type 2 Diabetes (A1c ≥ 6.5% and/or fasting plasma glucose >125mg/dL)
3. Bleeding disorders
4. Hemoglobin level < 12.5 g/dL for women; < 13.0 g/dL for men
5. Acute or chronic infections
6. Hepatitis and/or cirrhosis (AST or Alanine Aminotransferase 2.5 times upper limit of normal)
7. Severe asthma or chronic obstructive pulmonary disease
8. Renal insufficiency (creatinine > 1.6 mg/dL)
9. Prior bariatric surgery
10. Inflammatory bowel disease or malabsorption
11. Cancer within the last 3 years (except non-melanoma skin cancer or treated cervical carcinoma in situ)
12. Psychiatric or eating disorders
13. Untreated or inadequately controlled thyroid (abnormal TSH) or other endocrine disorders
14. Active rheumatoid arthritis or other inflammatory rheumatic disorder
15. Pregnant or nursing women
16. Presence of clinically significant abnormalities on electrocardiogram
17. Smoking (within the last 3 months)
18. Known hypersensitivity to nesiritide or any of its excipients
19. Poor intravenous access
20. 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 cyclooxygenase-2 inhibitors, g) other drugs known to affect immune or metabolic function and h) orlistat, phenteramine or other weight loss or anorectic agents.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Obese nondiabetic insulin resistant subjects- Panel A	Continous IV infusion of Nesiritide	IV nesiritide 3 pmol/kg/min or placebo for nesiritide
Obese nondiabetic insulin resistant subjects- Panel A	Hyperinsulinemic euglycemic clamp	IV nesiritide 3 pmol/kg/min or placebo for nesiritide
Obese nondiabetic insulin resistant subjects- Panel A	Placebo	IV nesiritide 3 pmol/kg/min or placebo for nesiritide
Obese nondiabetic insulin resistant subjects- Panel B	Continous IV infusion of Nesiritide	IV nesiritide 2 pmol/kg/min or placebo for nesiritide
Obese nondiabetic insulin resistant subjects- Panel B	Hyperinsulinemic euglycemic clamp	IV nesiritide 2 pmol/kg/min or placebo for nesiritide
Obese nondiabetic insulin resistant subjects- Panel B	Placebo	IV nesiritide 2 pmol/kg/min or placebo for nesiritide

Primary Outcome Measures

Name	Time	Method
IV infusion of nesiritide at a 3pmol/kg rate	48 hours	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.

Trial Locations

Locations (1)

Translational Research Institute for Metabolism and Diabetes; 🇺🇸 Orlando, Florida, United States