Role of Prostaglandins in the Regulation of Brain Blood Flow
Information source: National Institutes of Health Clinical Center (CC)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy; Hypercapnia
Sponsored by: National Institutes of Health Clinical Center (CC)
This study will use magnetic resonance imaging (MRI) to examine the role of prostaglandins-a
type of fatty acid with hormone-like actions-in the regulation of brain blood flow. The
results will provide information on how to better use this technique to study brain function,
which, in turn, may lead to a better understanding of certain illnesses and more effective
Healthy normal volunteers 18 years of age and older may be eligible for this study.
Participants will fill out a health questionnaire and undergo a history, physical examination
and MRI studies. MRI is a diagnostic tool that uses a strong magnetic field and radio waves
instead of X-rays to show structural and chemical changes in tissues. During the scanning,
the subject lies on a table in a narrow cylinder containing a magnetic field. An intercom
system allows the subject to speak with the staff member performing the study at all times
during the procedure. Four separate studies will be done-two carbon dioxide inhalation
studies and two functional activation studies-as follows:
Carbon dioxide inhalation (indomethacin): This study is done in two parts. In both parts, an
MRI brain scan is done. During the scan, the subject inhales an air mixture containing 6%
carbon dioxide through a facemask or mouthpiece. Blood pressure and heart rate are monitored
during inhalation of the mixture. For the second part of the study, indomethacin-a
non-steroidal anti-inflammatory drug-is injected through a catheter (thin flexible tube) in
an arm vein. Indomethacin inhibits prostaglandin production. Total scan time averages
between 45 and 90 minutes, with a maximum of 2 hours.
Carbon dioxide inhalation (rofecoxib and celecoxib): This study is identical to the one
above, except either rofecoxib or celecoxib is given instead of indomethacin. Both of these
drugs are also non-steroidal anti-inflammatory drugs that inhibit prostaglandin production.
Unlike indomethacin, rofecoxib and celecoxib are given orally instead of through a vein, so,
to allow time for the drug to be absorbed, the second scan is delayed for 2 hours.
Functional activation (indomethacin): This study is done in two parts. In both parts, a MRI
brain scan is done. During the study, the subject performs a simple motor task, such as
finger tapping. For the second part of the study, indomethacin is injected through a
catheter in an arm vein.
Functional activation (rofecoxib and celecoxib): This study is identical to the indomethacin
functional activation study, except either rofecoxib or celecoxib is given instead of
indomethacin. Because they are given orally instead of through a vein, the second scan is
delayed 2 hours to allow time for the drug to be absorbed.
Official title: Role of Prostaglandins in the Control of Cerebral Blood Flow During Hypercapnia and Functional Activation in Humans
Study design: N/A
Advances in MR perfusion imaging have provided clinical researchers with the opportunity to
quantify regional increases in cerebral blood flow. The purpose of this study is to
investigate in humans the role of prostaglandins in the regulation of cerebral blood flow
during hypercapnia and functional activation. For this investigation the increase in
cerebral blood flow associated with either hypercapnia or functional activation will be
measured before and after the administration of pharmacological agents that inhibit the
production of prostaglandins. In the hypercapnia study cerebral blood flow will be increased
by inhalation of an air mixture containing 6% CO2. For the functional activation study
cerebral blood flow will be increased by a sensory motor task.
Minimum age: N/A.
Maximum age: N/A.
Any healthy normal volunteer above the age of 18 who is capable of giving informed
Subjects will be excluded for the following reasons.
They have contraindications to MR scanning, such as the following: aneurysm clip, implanted
neural stimulator, implanted cardiac pacemaker or autodefibrillator, cochlear implant,
ocular foreign body (e. g., metal shavings), or insulin pump.
They have panic disorder or migraine (because of possible complications with CO2
They have cirrhosis, any renal dysfunction, or a chronic respiratory illness (such as
They have allergies to sulfonamide drugs or cyclo-oxygenase inhibitors (NSAIDS).
Locations and Contacts
Warren G. Magnuson Clinical Center (CC), Bethesda, Maryland 20892, United States
O'Banion MK. Cyclooxygenase-2: molecular biology, pharmacology, and neurobiology. Crit Rev Neurobiol. 1999;13(1):45-82. Review.
Kaufmann WE, Worley PF, Pegg J, Bremer M, Isakson P. COX-2, a synaptically induced enzyme, is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex. Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2317-21.
Yamagata K, Andreasson KI, Kaufmann WE, Barnes CA, Worley PF. Expression of a mitogen-inducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids. Neuron. 1993 Aug;11(2):371-86.
Starting date: September 2000
Ending date: December 2003
Last updated: March 3, 2008