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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2012 by Washington University School of Medicine.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Robert Gropler, Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00603720
First received: January 16, 2008
Last updated: March 7, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention
Cardiovascular Diseases
Procedure: Positron Emission Tomography (PET)
Drug: L-NAME
Drug: L-Arginine
Drug: Phenylephrine

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: PET Detection of the Effects of Aging on the Human Heart. Aim#1-Impact of Aging on Myocardial Remodeling: Role of Nitric Oxide

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Changes in the level of cardiac fat and glucose metabolism and function before and during L-NAME and L-arginine infusions [ Time Frame: with each of 3 PET scans ] [ Designated as safety issue: No ]

Estimated Enrollment: 105
Study Start Date: September 2005
Estimated Study Completion Date: September 2012
Estimated Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: B
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.
Procedure: Positron Emission Tomography (PET)
3 PET scans of about 1 hour each for each study day
Drug: L-NAME
nitric oxide synthase inhibitor 4mg/kg infusion over 30-60 minutes prior to PET imaging
Other Name: N (G)-nitro-L- arginine methyl ester
Drug: L-Arginine
aids in nitric oxide production
Active Comparator: C
25 individuals age 18-35 will be getting an infusion of phenylephrine (primarily an alpha agonist) during 3 separate PET study days
Procedure: Positron Emission Tomography (PET)
3 PET scans of about 1 hour each for each study day
Drug: Phenylephrine
alpha agonist; 10 μg/kg/min infusion during PET study
Active Comparator: D
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
Procedure: Positron Emission Tomography (PET)
3 PET scans of about 1 hour each for each study day
Drug: L-Arginine
aids in nitric oxide production
Experimental: E
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
Procedure: Positron Emission Tomography (PET)
3 PET scans of about 1 hour each for each study day
Drug: L-Arginine
aids in nitric oxide production
Experimental: F
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
Procedure: Positron Emission Tomography (PET)
3 PET scans of about 1 hour each for each study day
Drug: L-NAME
nitric oxide synthase inhibitor 4mg/kg infusion over 30-60 minutes prior to PET imaging
Other Name: N (G)-nitro-L- arginine methyl ester
Drug: L-Arginine
aids in nitric oxide production

Detailed Description:

Aging is associated with an increased incidence and severity of various cardiovascular disorders. Previously, our laboratory has demonstrated an age-related shift in the substrates used by the heart for metabolism from primarily fatty acids to primarily glucose. Furthermore, other institutions have demonstrated that a similar shift can be induced, in animal models, with specific nitric oxide synthase inhibitors, such as L-NAME (N-Nitro-L-Arginine Methyl Ester). Our hypothesis is that a reduction in nitric oxide (NO) synthesis is responsible for the age-related shift in heart function. Accordingly, we aim to demonstrate, in young patients, an acute, transient shift in substrate use from fatty acids to glucose with L-NMMA (citrate) in association with depressed heart function. Also, we aim to demonstrate in the elderly an acute, transient shift in substrate use from glucose to fatty acids with L-arginine, in association with improved cardiac function. These results will demonstrate a portion of the mechanism for the age-related shift in substrate utilization.

Each participant will undergo a screening visit which will include a Glucose Tolerance Test, an echocardiogram in conjunction with a treadmill stress test to exclude cardiac disease, and baseline blood work. Then each patient will have 3 PET study days, each lasting about 5-6 hours. During this time, the patient will have two IVs (one in each arm). They will have 4 injections of different radioactive isotopes (015 Water, C11 Acetate, C11 Glucose, and C11 Palmitate). After each injection, about 8-10 blood samples will be drawn over the course of about ½ to 1 hour of time. In between each injection, there will be about an hour break for the patient to rest and move around. During one of the breaks, the patient will have another echocardiogram. On the day 2 and 3 PET, the patient will have a 30-60 minute infusion of L-NAME. Then the PET study will commence. After the study is over the participant will have a 10-minute infusion of L-arginine to reverse the effects of L-NAME.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00603720

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Robert Gropler, MD Washington University School of Medicine
  More Information

Publications:
Responsible Party: Robert Gropler, Professor of Radiology, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00603720     History of Changes
Other Study ID Numbers: AG0086, 5R01AG015466-08, 05-0810, RDRC# 482F, GCRC# 1002
Study First Received: January 16, 2008
Last Updated: March 7, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Washington University School of Medicine:
PET
Heart metabolism
Nitric oxide
Myocardial remodeling

Additional relevant MeSH terms:
Cardiovascular Diseases
Nitric Oxide
Phenylephrine
Oxymetazoline
NG-Nitroarginine Methyl Ester
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Cardiovascular Agents
Protective Agents
Adrenergic alpha-1 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Cardiotonic Agents
Mydriatics
Sympathomimetics
Vasoconstrictor Agents
Nasal Decongestants

ClinicalTrials.gov processed this record on April 15, 2014