Regression of Myocardial Steatosis by Nebivolol - Full Text View

Purpose

Within large number of patients with obesity, it is crucial to determine who is at the greatest risk for development of chronic heart disease. The investigators previous studies suggest that an excessive accumulation of fat in heart cells precedes the development of obesity-related pathologies and may serve as a biomarker of heart disease in high-risk population. Until now, the evaluation of fat in the human heart was possible postmortem or by biopsy. The investigators novel magnetic resonance spectroscopy technique enables the quantification of intracellular lipid content non-invasively and repeatedly in humans in vivo. It could be used to better screen and treat obese patients at risk for the development of metabolic disease. The investigators hypothesize that in obese humans with elevated myocardial triglycerides, treatment with Nebivolol will reduce myocardial fat and will improve heart function.

Condition	Intervention
Cardiac Steatosis and Lipotoxicity	Drug: Nebivolol

Study Type:	Interventional
Study Design:	Endpoint Classification: Pharmacodynamics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment

Resource links provided by NLM:

MedlinePlus related topics: Obesity

Drug Information available for: Nebivolol Nebivolol Hydrochloride

U.S. FDA Resources

Further study details as provided by Cedars-Sinai Medical Center:

Primary Outcome Measures:

Myocardial triglyceride content [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Regression of myocadial triglycerides using MR spectroscopy at two time points, one prior to receiving Nebivolol and six months after continuous low dose Nebivolol treatment.

Secondary Outcome Measures:

Cardiac function [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Cardiac systolic and diastolic function will be assessed with cardiac MRI at two time points, one prior to receiving low dose Nebivolol treatment and once after six months of Nebivolol treatment.
Regression of concentric cardiac remodeling [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Cardiac concentric remodeling will be assessed with cardiac MRI at two time points, one prior to receiving low dose Nebivolol treatment and once after six months of Nebivolol treatment.
Regression of steatosis in other non-adipocyte tissue [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Regression of steatosis in other non-adipocyte tissue, including skeletal muscle, liver, and pancreas, will be assessed with MR spectroscopy at two time points, one prior to receiving low dose Nebivolol treatment and once after six months of Nebivolol treatment.
Regression of subcutaneous fat [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Regression of subcutaneous fat will be assessed with cardiac MRI at two time points, one prior to receiving low dose Nebivolol treatment and once after six months of Nebivolol treatment.

Estimated Enrollment:	30
Study Start Date:	June 2011
Estimated Study Completion Date:	June 2013
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Nebivolol Nebivolol (Bystolic® by Forest/Mylan) is a third-generation beta-blocker; it selectively blocks β1-adrenergic receptors and increases peripheral vasodilation.	Drug: Nebivolol Day 1 - Patients will start Nebivolol 5 mg PO daily; after one month, if the subject has tolerated 5 mg PO Nebivolol, the dose will be increased to 10 mg PO daily. If the patients is unable to tolerate 5 mg PO Nebivolol, he/she will be discontinued from the study. After six months, medication will be tapered to 5 mg PO daily for two weeks. Medication will then be tapered to 2.5 mg PO daily for two additional weeks. Other Name: Bystolic® by Forest/Mylan

Arms

Assigned Interventions

Experimental: Nebivolol

Nebivolol (Bystolic® by Forest/Mylan) is a third-generation beta-blocker; it selectively blocks β1-adrenergic receptors and increases peripheral vasodilation.

Drug: Nebivolol

Day 1 - Patients will start Nebivolol 5 mg PO daily; after one month, if the subject has tolerated 5 mg PO Nebivolol, the dose will be increased to 10 mg PO daily. If the patients is unable to tolerate 5 mg PO Nebivolol, he/she will be discontinued from the study. After six months, medication will be tapered to 5 mg PO daily for two weeks. Medication will then be tapered to 2.5 mg PO daily for two additional weeks.

Other Name: Bystolic® by Forest/Mylan

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 59 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Mexican American men and women
Age 18 - 59
Metabolic Syndrome*
Myocardial TG > or = to 0.5% by localized MR spectroscopy

*Metabolic syndrome in our study will follow the NCEP ATP III (National Cholesterol Education Program Adult Treatment Panel III) Guidelines which include > or = to 3 of the following:
Fasting blood glucose > or = to 100 mg/dL
Waist circumference: Men > 102 cm, Women > 88 cm
Triglycerides > or = to 150 mg/dL
BP > 130/85

Exclusion Criteria:

Current use of a beta-blocker
HR < 50 beats/min or BP < 130/85
Contraindication to beta-blocker therapy such as asthma, reactive airway disease, heart block, or depression
CHF (any NYHA class) by history, physical examination, or current use of CHF medication including beta-blockers, ACE inhibitors, angiotensin receptor blockers (ARBs), diuretics, calcium channel blockers, digitoxin, hydralazine, nitrates (including sublingual nitroglycerin), and inotropic agents
LVEF < 50% by cardiac MRI
Hepatic insufficiency or current use of another medication that is also metabolized by the CYP2D6 isozyme (paroxetine, fluoxetine, quinidine, propafenone).
Any contraindication to MRI, e.g. metallic implants, metallic tattoos, claustrophobia, weight > 350 pounds (the MRI weight limit)
Pregnancy at any time during the study
A recent weight loss (>10% of body weight within the past year) or plans to undergo significant weight reduction (>10% of body weight) during the experimental protocol.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01358409

Locations

United States, California
Cedars-Sinai Medical Center	Not yet recruiting
Los Angeles, California, United States, 90048
Contact: Gonzalez 310-248-8094 obesity.research@cshs.org
Contact: Szczepaniak lidia.szczepaniak@cshs.org

Sponsors and Collaborators

Cedars-Sinai Medical Center

Forest Laboratories

Investigators

Principal Investigator:

Lidia S Szczepaniak, PhD

Cedars-Sinai Heart Institute

More Information

No publications provided

Responsible Party:	Lidia Szczepaniak, principle investigator, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier:	NCT01358409 History of Changes
Other Study ID Numbers:	MTG_Neb01
Study First Received:	May 20, 2011
Last Updated:	May 20, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Cedars-Sinai Medical Center:

steatosis
MR spectroscopy
Nebivolol
cardiac MRI

Additional relevant MeSH terms:

Nebivolol
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Vasodilator Agents
Adrenergic beta-1 Receptor Antagonists

Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 19, 2013