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Sponsored by: |
National Institute on Aging (NIA) |
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Information provided by: | National Institute on Aging (NIA) |
ClinicalTrials.gov Identifier: | NCT00603720 |
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 |
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Cardiovascular Diseases |
Procedure: Positron Emission Tomography (PET) Drug: L-NAME Drug: L-Arginine Drug: Phenylephrine |
Study Type: | Interventional |
Study Design: | Basic Science, Non-Randomized, Open Label, Parallel Assignment, Pharmacokinetics/Dynamics Study |
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 |
Estimated Enrollment: | 105 |
Study Start Date: | September 2005 |
Estimated Study Completion Date: | September 2009 |
Estimated Primary Completion Date: | September 2009 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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B: 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.
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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
Drug: L-Arginine
aids in nitric oxide production
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C: Active Comparator
25 individuals age 18-35 will be getting an infusion of phenylephrine (primarily an alpha agonist) during 3 separate PET study days
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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
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D: 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
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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
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E: Experimental
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
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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
|
F: 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
|
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
Drug: L-Arginine
aids in nitric oxide production
|
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.
Ages Eligible for Study: | 18 Years to 75 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
Contact: Jeff Baumstark, MS | 314-747-8860 | baumstarkj@mir.wustl.edu |
Contact: Amanda DeMoss | 314-362-7351 | demossa@mir.wustl.edu |
United States, Missouri | |
Washington University School of Medicine | Recruiting |
St. Louis, Missouri, United States, 63110 | |
Contact: Jeff Baumstark, MS 314-747-8860 baumstarkj@mir.wustl.edu | |
Contact: Amanda DeMoss, MS 314-362-7351 demossa@mir.wustl.edu | |
Principal Investigator: Robert Gropler, MD | |
Sub-Investigator: Pablo Soto, MD | |
Sub-Investigator: Linda Peterson, MD | |
Sub-Investigator: Pilar Herrero, MS |
Principal Investigator: | Robert Gropler, MD | Washington University School of Medicine |
Responsible Party: | Washington University in St Louis ( Robert Gropler, MD ) |
Study ID Numbers: | AG0086, 5R01AG01546608, RDRC# 482F, GCRC# 1002 |
Study First Received: | January 16, 2008 |
Last Updated: | October 30, 2008 |
ClinicalTrials.gov Identifier: | NCT00603720 |
Health Authority: | United States: Food and Drug Administration |
PET Heart metabolism Nitric oxide Myocardial remodeling |
Pseudoephedrine Nitric Oxide Naphazoline Oxymetazoline NG-Nitroarginine Methyl Ester |
Guaifenesin Phenylephrine Ephedrine Phenylpropanolamine |
Respiratory System Agents Neurotransmitter Agents Vasodilator Agents Antioxidants Molecular Mechanisms of Pharmacological Action Adrenergic Agents Cardiotonic Agents Physiological Effects of Drugs Adrenergic Agonists Nasal Decongestants Therapeutic Uses Free Radical Scavengers Vasoconstrictor Agents |
Endothelium-Dependent Relaxing Factors Cardiovascular Diseases Adrenergic alpha-Agonists Sympathomimetics Anti-Asthmatic Agents Enzyme Inhibitors Cardiovascular Agents Protective Agents Pharmacologic Actions Mydriatics Autonomic Agents Peripheral Nervous System Agents Bronchodilator Agents |