Role of Nitric Oxide in the Impact of Aging on Myocardial Remodeling

NCT00603720 | Completed Results

• 5 other identifiers: AG00865R01AG015466-0805-0810RDRC# 482FGCRC# 1002
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine, with Positron Emission Tomography (PET), the role of nitric oxide in the age-associated effect on fatty acid and glucose delivery on myocardial substrate metabolism.

Conditions

Cardiovascular Diseases

Keywords

PET; Heart metabolism; Nitric oxide; Myocardial remodeling

Outcome Measures

Primary Outcomes (1)

• Effect of NO Inhibition on Myocardial Substrate Metabolism in Humans

  Determine in young healthy volunteers the extent to which acute inhibition of nitric oxide production will effect a shift in myocardial substrate utilization characterized as a decline in myocardial fatty acid oxidation, and perhaps myocardial fatty acid utilization, and increase in myocardial glucose uptake, and whether these changes are associated with a decline in LV function.

  1-3 months

Study Arms (5)

L-Name in Young

ACTIVE COMPARATOR

20 individuals age 18-35 will be getting an infusion of L-NAME (a nitric oxide inhibitor) during 3 separate PET study days, then a 10-minute infusion of L-arginine to reverse effects of L-NAME.

Drug: L-NAME

Phenylephrine

ACTIVE COMPARATOR

25 individuals age 18-35 will be getting an infusion of phenylephrine (primarily an alpha agonist) during 3 separate PET study days

Drug: Phenylephrine

L-arginine in Young

ACTIVE COMPARATOR

20 individuals age 18-35 will be getting an infusion of L-arginine 125 mcg/kg/min for 120 to 140 minutes during 3 separate PET study days

Drug: L-Arginine

L-arginine in Old

ACTIVE COMPARATOR

20 individuals age 60-75 will be getting an infusion of L-arginine 125 mcg/kg/min for 120 to 140 minutes during 3 separate PET study days

Drug: L-Arginine

L-NAME in Old

EXPERIMENTAL

20 individuals age 60-75 will be getting an infusion of L-NAME (a nitric oxide inhibitor) during 3 separate PET study days, then a 10-minute infusion of L-arginine to reverse effects of L-NAME

Drug: L-NAME

Interventions

L-NAME DRUG

nitric oxide synthase inhibitor 4mg/kg infusion over 30-60 minutes prior to PET imaging

Also known as: N (G)-nitro-L- arginine methyl ester

L-NAME in Old; L-Name in Young

L-Arginine DRUG

aids in nitric oxide production

Also known as: 2-Amino-5-guanidinopentanoic acid

L-arginine in Old; L-arginine in Young

Phenylephrine DRUG

alpha agonist; 10 μg/kg/min infusion during PET study

Also known as: (R)-3-[-1-hydroxy-2-(methylamino)ethyl]phenol

Phenylephrine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between the ages of 18-35 or 60-75
• Normal glucose tolerance test
• Normal plasma fasting lipid panel (fasting total cholesterol less than 220 mg/dL)
• Normal rest/stress echocardiogram
• BMI (Body Mass Index) less than 30 kg/m2

You may not qualify if:

• Coronary artery disease
• High blood pressure
• Current smoker
• Diabetes mellitus
• Cardiovascular disease (signs and symptoms of any kind)
• History of stroke, peripheral vascular disease, or arrhythmia
• Pregnant or breastfeeding

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (4)

• Ogawa T, Spina RJ, Martin WH 3rd, Kohrt WM, Schechtman KB, Holloszy JO, Ehsani AA. Effects of aging, sex, and physical training on cardiovascular responses to exercise. Circulation. 1992 Aug;86(2):494-503. doi: 10.1161/01.cir.86.2.494.

  PMID: 1638717 BACKGROUND

• Olivetti G, Melissari M, Capasso JM, Anversa P. Cardiomyopathy of the aging human heart. Myocyte loss and reactive cellular hypertrophy. Circ Res. 1991 Jun;68(6):1560-8. doi: 10.1161/01.res.68.6.1560.

  PMID: 2036710 BACKGROUND

• Coughlin SS, Neaton JD, Sengupta A, Kuller LH. Predictors of mortality from idiopathic dilated cardiomyopathy in 356,222 men screened for the Multiple Risk Factor Intervention Trial. Am J Epidemiol. 1994 Jan 15;139(2):166-72. doi: 10.1093/oxfordjournals.aje.a116978.

  PMID: 8296783 BACKGROUND

• Haldeman GA, Croft JB, Giles WH, Rashidee A. Hospitalization of patients with heart failure: National Hospital Discharge Survey, 1985 to 1995. Am Heart J. 1999 Feb;137(2):352-60. doi: 10.1053/hj.1999.v137.95495.

  PMID: 9924171 BACKGROUND

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

NG-Nitroarginine Methyl Ester; Arginine; Phenylephrine

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Limitations and Caveats

There were no limitations or caveats

Results Point of Contact

• Title: Robert Gropler, MD, Chief of Cardiovascular Imaging Laboratory
• Organization: Washington University School of Medicine

groplerr@mir.wustl.edu

314-747-3877

Study Officials

• Robert Gropler, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2008
• First Posted: January 29, 2008
• Study Start: September 1, 2005
• Primary Completion: June 1, 2008
• Study Completion: June 1, 2008
• Last Updated: September 12, 2018
• Results First Posted: September 12, 2018

Record last verified: 2018-09

Locations

US (1)