Role of Prostaglandins in the Regulation of Brain Blood Flow

Tracking Information
First Submitted Date	September 30, 2000
First Posted Date	October 2, 2000
Last Update Posted Date	March 4, 2008
Study Start Date	September 2000
Primary Completion Date	Not Provided
Current Primary Outcome Measures	Not Provided
Original Primary Outcome Measures	Not Provided
Change History	Complete list of historical versions of study NCT00006318 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures	Not Provided
Original Secondary Outcome Measures	Not Provided
Current Other Outcome Measures	Not Provided
Original Other Outcome Measures	Not Provided
Descriptive Information
Brief Title	Role of Prostaglandins in the Regulation of Brain Blood Flow
Official Title	Role of Prostaglandins in the Control of Cerebral Blood Flow During Hypercapnia and Functional Activation in Humans
Brief Summary	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 treatments. 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.
Detailed Description	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.
Study Type	Observational
Study Design	Not Provided
Target Follow-Up Duration	Not Provided
Biospecimen	Not Provided
Sampling Method	Not Provided
Study Population	Not Provided
Condition	Healthy; Hypercapnia
Intervention	Not Provided
Study Groups/Cohorts	Not Provided
Publications *	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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status	Completed
Enrollment; (submitted: June 23, 2005)	125
Original Enrollment	Same as current
Study Completion Date	December 2003
Primary Completion Date	Not Provided
Eligibility Criteria	INCLUSION CRITERIA: Any healthy normal volunteer above the age of 18 who is capable of giving informed consent. EXCLUSION CRITERIA: 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 inhalation). They have cirrhosis, any renal dysfunction, or a chronic respiratory illness (such as asthma). They have allergies to sulfonamide drugs or cyclo-oxygenase inhibitors (NSAIDS).
Sex/Gender	Sexes Eligible for Study: All
Ages	Child, Adult, Senior
Accepts Healthy Volunteers	Yes
Contacts	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries	United States
Removed Location Countries
Administrative Information
NCT Number	NCT00006318
Other Study ID Numbers	000226; 00-CC-0226
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Not Provided
Study Sponsor	National Institutes of Health Clinical Center (CC)
Collaborators	Not Provided
Investigators	Not Provided
PRS Account	National Institutes of Health Clinical Center (CC)
Verification Date	December 2003