HealthyNCT00044200
Positron Emission Tomography (PET) to Study Brain Signaling
An observational study of Healthy, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
This study uses positron emission tomography (PET) to examine brain function and signaling involving phospholipids, and to see how signaling is related to blood flow. Much of the brain is composed of fatty molecules called phospholipids. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Healthy
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jan 2000to 12 Jun 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- All subjects must have normal values on screening measures to be in the study.
- Age between 18 and 45 years.
Who cannot join
- Past or current medical condition that would interfere with brain function- history of alcoholism; psychiatric or neurological illness; head trauma with loss of consciousness; history of exposure to central nervous system toxin; history of central nervous system infection; metabolic, endocrine, connective tissue disease; hypertension or other cardiovascular disorder; abnormal renal, liver or pulmonary function; blood or coagulation disease; malignancy; psychopharmacological treatment; neurodegenerative or neurodevelopmental disorder; stroke; epilepsy; sensitivity to flashing lights. Subjects requiring regular medication.
- Subjects demonstrated by drug screening to have taken controlled substance.
- For female subjects, pregnancy or current breast-feeding (nursing).
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Positron Emission Tomography Imaging of Activation-Induced Signal Transduction in Human Brain
This study uses positron emission tomography (PET) to examine brain function and signaling involving phospholipids, and to see how signaling is related to blood flow. Much of the brain is composed of fatty molecules called phospholipids. These molecules are involved in the way brain cells signal each other to direct brain function. Brain disease may change phospholipids and disturb brain structure and signaling. Studies of brain phospholipid composition and metabolism may help clarify how the brain works in healthy people or stops working effectively in disease states.
Healthy volunteers between 18 and 45 years of age may be eligible for this study. Candidates are screened with a medical history, physical examination, and blood and urine tests. Participants undergo magnetic resonance imaging (MRI) and PET scanning as follows:
Read more
MRI
MRI uses a magnetic field and radio waves to produce images of body tissues and organs. For this procedure, the subject lies on a table that is moved into a metal cylinder (the scanner) and wears earplugs to muffle loud knocking and thumping sounds that occur during the scanning process. Scanning time varies from 20 minutes to 3 hours, with most scans lasting between 45 and 90 minutes. Subjects may be asked to lie still for up to 30 minutes at a time.
PET
For the PET scan, a catheter (thin plastic tube) is inserted into an artery in the subject's wrist or elbow crease to collect blood samples during the procedure, and a second catheter is placed in a vein in the opposite arm to inject radioactive tracers. The subject lies on the scanner bed, wearing a special facemask and goggles. The mask helps hold the head still during the scans, and the goggles either block all light or administer bright flashing lights. Radioactive water is injected into the vein, followed by a 1-minute PET scan to measure brain blood flow. This is repeated three more times. Then, a radioactive fatty acid is injected into the vein, followed by a 1-hour PET scan to measure brain phospholipid metabolism. This is repeated once. The images of blood flow and phospholipid metabolism in the different regions of the brain under the conditions of darkness and during visual stimulation provide information on how and where the brain responds to visual stimulation. The entire procedure takes about 3 hours.
Read the detailed description
Objective
The binding of neurotransmitters and certain drugs to neuroreceptors in the brain is considered to modify cognition and behavior by activating certain receptor-coupled effector enzymes and initiating signal transduction cascades. One of these effector enzymes is phospholipase A2 (PLA2), which when activated will release arachidonic acid (AA) from phospholipids and initiate the AA cascade (Fitzpatrick and Soberman, 2001). AA and its eicosanoid metabolites have multiple biological actions. We have developed an imaging method to quantify and localize brain signal transduction involving PLA2 and AA in unanesthetized rats and monkeys, using quantitative autoradiography or positron emission tomography (PET), and radiolabeled AA. The aim of this protocol is to extend this method to humans with PET, when brain imaging AA signaling in two experimental conditions (dark and visual flash stimulation at a frequency of 3 Hz or 8Hz) in the same subject in the same PET session. Radioactive [1-11C]AA will be injected intravenously in each condition, and PET will be used to measure its incorporation coefficient k* in individual brain regions. Animal studies and modeling have shown that the incorporation coefficient is proportion to PLA2 activation and the release of AA from brain phospholipids (Rapoport, 2003). In addition, [15O]H20 will be injected in each condition to measure regional cerebral blood flow (rCBF). Based on our prior studies in human subjects of rCBF during visual activation by flashing lights at different frequencies (Mentis et al., 1997; Mentis et al., 1998; Mentis et al., 1996), we hypothesize that statistically significant increments in rCBF and [11C]AA incorporation into brain will be increased during visual activation compared with the dark (unactivated) condition. These increments should be evident in primary visual cortex, association visual cortex, thalamus, and frontal cortex. If our hypothesis proves correct and our method to measure [11C]AA incorporation both during stimulation and in the dark proves feasible in the same subject in the PET session, we believe that the method could be applied generally in humans to examine brain PLA2-related signal transduction during physiological or pharmacological activation and in healthy aging (Giovacchini et al., In press) and disease, particularly Parkinson and Alzheimer disease (Hayakawa et al., 2001; Nariai et al., 1991).
Study population
We plan to study 30 normal volunteers, each of whom will be subjected two stimulation conditions in the same PET session, visual stimulation at a frequency of 3 or 8 Hz, or a dark condition (0 Hz).
Design
Each PET scan session will last approximately 3 hours. Each subject will receive a total of four [15O]H20 injections to measure regional cerebral blood flow (rCBF), and two [11C]AA infusions to measure incorporation k* for AA during a single PET scan session. He/she will have an arterial catheter and venous line inserted during the entire session, and one transmission scan at the beginning of the session. The order of the scans will be randomized. The order of 4 blood flow scans will be: Rest-Photic Activation-Photic Activation-Rest OR Photic Activation-Rest-Rest-Photic Activation. The order of two [C11]AA scans will be Rest-Photic Stimulation Or Photic Stimulation-Rest.
Stimulation will be conducted via LED goggles at a flash frequency of 3 Hz and 8 Hz, evenly divided among the 30 subjects, and at 0 Hz (dark condition). Statistical parametric mapping and other statistical procedures will be used to identify brain regions in which k* for AA and/or rCBF is elevated at 3 Hz compared with the dark condition; at 8 Hz compared with the dark condition; and at 8 Hz compared with 3 Hz condition.
- Conditions
- Healthy
- Keywords
- Phospholipase A2, Arachidonic Acid, Blood Flow, Coupling, Neurotransmission, PET, Signal Transduction, Activation, Brain, [15O]H20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2002 (estimated)
- Study start10 Jan 2000
- Study completion12 Jun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Stanley I Rapoport, M.D., Principal investigator, National Institute on Aging (NIA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00044200
- Sponsor's protocol ID
- 000057
- Other IDs
- 00-N-0057
- Status last verified
- 12 Jun 2015
- First submitted
- 21 Aug 2002
- Last updated
- 5 Jul 2018
- Results posted
- No
Publications
Arai T, Wakabayashi S, Channing MA, Dunn BB, Der MG, Bell JM, Herscovitch P, Eckelman WC, Rapoport SI, Chang MC. Incorporation of [1-carbon-11]palmitate in monkey brain using PET. J Nucl Med. 1995 Dec;36(12):2261-7.
PubMed 8523117Axelrod J. Phospholipase A2 and G proteins. Trends Neurosci. 1995 Feb;18(2):64-5. doi: 10.1016/0166-2236(95)93873-v. No abstract available.
PubMed 7537411Axelrod J. Receptor-mediated activation of phospholipase A2 and arachidonic acid release in signal transduction. Biochem Soc Trans. 1990 Aug;18(4):503-7. doi: 10.1042/bst0180503. No abstract available.
PubMed 2177403
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Positron Emission Tomography Imaging of Activation-Induced Signal Transduction in Human Brain
- ClinicalTrials.gov ID
- NCT00044200
- Acronym / sponsor ID
- 000057
- Conditions
- Healthy
- Keywords
- Phospholipase A2, Arachidonic Acid, Blood Flow, Coupling, Neurotransmission, PET, Signal Transduction, Activation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 10 Jan 2000
- Study completion
- 12 Jun 2015
- First posted
- 22 Aug 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study uses positron emission tomography (PET) to examine brain function and signaling involving phospholipids, and to see how signaling is related to blood flow. Much of the brain is composed of fatty molecules called phospholipids. These molecules are involved in the way brain cells signal each other to direct brain function. Brain disease may change phospholipids and disturb brain structure and signaling. Studies of brain phospholipid composition and metabolism may help clarify how the brain works in healthy people or stops working effectively in disease states.
Healthy volunteers between 18 and 45 years of age may be eligible for this study. Candidates are screened with a medical history, physical examination, and blood and urine tests. Participants undergo magnetic resonance imaging (MRI) and PET scanning as follows:
MRI
MRI uses a magnetic field and radio waves to produce images of body tissues and organs. For this procedure, the subject lies on a table that is moved into a metal cylinder (the scanner) and wears earplugs to muffle loud knocking and thumping sounds that occur during the scanning process. Scanning time varies from 20 minutes to 3 hours, with most scans lasting between 45 and 90 minutes. Subjects may be asked to lie still for up to 30 minutes at a time.
PET
For the PET scan, a catheter (thin plastic tube) is inserted into an artery in the subject's wrist or elbow crease to collect blood samples during the procedure, and a second catheter is placed in a vein in the opposite arm to inject radioactive tracers. The subject lies on the scanner bed, wearing a special facemask and goggles. The mask helps hold the head still during the scans, and the goggles either block all light or administer bright flashing lights. Radioactive water is injected into the vein, followed by a 1-minute PET scan to measure brain blood flow. This is repeated three more times. Then, a radioactive fatty acid is injected into the vein, followed by a 1-hour PET scan to measure brain phospholipid metabolism. This is repeated once. The images of blood flow and phospholipid metabolism in the different regions of the brain under the conditions of darkness and during visual stimulation provide information on how and where the brain responds to visual stimulation. The entire procedure takes about 3 hours.
Detailed description
Objective
The binding of neurotransmitters and certain drugs to neuroreceptors in the brain is considered to modify cognition and behavior by activating certain receptor-coupled effector enzymes and initiating signal transduction cascades. One of these effector enzymes is phospholipase A2 (PLA2), which when activated will release arachidonic acid (AA) from phospholipids and initiate the AA cascade (Fitzpatrick and Soberman, 2001). AA and its eicosanoid metabolites have multiple biological actions. We have developed an imaging method to quantify and localize brain signal transduction involving PLA2 and AA in unanesthetized rats and monkeys, using quantitative autoradiography or positron emission tomography (PET), and radiolabeled AA. The aim of this protocol is to extend this method to humans with PET, when brain imaging AA signaling in two experimental conditions (dark and visual flash stimulation at a frequency of 3 Hz or 8Hz) in the same subject in the same PET session. Radioactive [1-11C]AA will be injected intravenously in each condition, and PET will be used to measure its incorporation coefficient k* in individual brain regions. Animal studies and modeling have shown that the incorporation coefficient is proportion to PLA2 activation and the release of AA from brain phospholipids (Rapoport, 2003). In addition, [15O]H20 will be injected in each condition to measure regional cerebral blood flow (rCBF). Based on our prior studies in human subjects of rCBF during visual activation by flashing lights at different frequencies (Mentis et al., 1997; Mentis et al., 1998; Mentis et al., 1996), we hypothesize that statistically significant increments in rCBF and [11C]AA incorporation into brain will be increased during visual activation compared with the dark (unactivated) condition. These increments should be evident in primary visual cortex, association visual cortex, thalamus, and frontal cortex. If our hypothesis proves correct and our method to measure [11C]AA incorporation both during stimulation and in the dark proves feasible in the same subject in the PET session, we believe that the method could be applied generally in humans to examine brain PLA2-related signal transduction during physiological or pharmacological activation and in healthy aging (Giovacchini et al., In press) and disease, particularly Parkinson and Alzheimer disease (Hayakawa et al., 2001; Nariai et al., 1991).
Study population
We plan to study 30 normal volunteers, each of whom will be subjected two stimulation conditions in the same PET session, visual stimulation at a frequency of 3 or 8 Hz, or a dark condition (0 Hz).
Design
Each PET scan session will last approximately 3 hours. Each subject will receive a total of four [15O]H20 injections to measure regional cerebral blood flow (rCBF), and two [11C]AA infusions to measure incorporation k* for AA during a single PET scan session. He/she will have an arterial catheter and venous line inserted during the entire session, and one transmission scan at the beginning of the session. The order of the scans will be randomized. The order of 4 blood flow scans will be: Rest-Photic Activation-Photic Activation-Rest OR Photic Activation-Rest-Rest-Photic Activation. The order of two [C11]AA scans will be Rest-Photic Stimulation Or Photic Stimulation-Rest.
Stimulation will be conducted via LED goggles at a flash frequency of 3 Hz and 8 Hz, evenly divided among the 30 subjects, and at 0 Hz (dark condition). Statistical parametric mapping and other statistical procedures will be used to identify brain regions in which k* for AA and/or rCBF is elevated at 3 Hz compared with the dark condition; at 8 Hz compared with the dark condition; and at 8 Hz compared with 3 Hz condition.
Study design
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- All subjects must have normal values on screening measures to be in the study.
- Age between 18 and 45 years.
Key exclusion criteria (3 listed)
- Past or current medical condition that would interfere with brain function- history of alcoholism; psychiatric or neurological illness; head trauma with loss of consciousness; history of exposure to central nervous system toxin; history of central nervous system infection; metabolic, endocrine, connective tissue disease; hypertension or other cardiovascular disorder; abnormal renal, liver or pulmonary function; blood or coagulation disease; malignancy; psychopharmacological treatment; neurodegenerative or neurodevelopmental disorder; stroke; epilepsy; sensitivity to flashing lights. Subjects requiring regular medication.
- Subjects demonstrated by drug screening to have taken controlled substance.
- For female subjects, pregnancy or current breast-feeding (nursing).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2018.
- Background: PubMed 8523117Arai T, Wakabayashi S, Channing MA, Dunn BB, Der MG, Bell JM, Herscovitch P, Eckelman WC, Rapoport SI, Chang MC. Incorporation of [1-carbon-11]palmitate in monkey brain using PET. J Nucl Med. 1995 Dec;36(12):2261-7.
- Background: PubMed 7537411Axelrod J. Phospholipase A2 and G proteins. Trends Neurosci. 1995 Feb;18(2):64-5. doi: 10.1016/0166-2236(95)93873-v. No abstract available.
- Background: PubMed 2177403Axelrod J. Receptor-mediated activation of phospholipase A2 and arachidonic acid release in signal transduction. Biochem Soc Trans. 1990 Aug;18(4):503-7. doi: 10.1042/bst0180503. No abstract available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stanley I Rapoport, M.D. principal investigator
National Institute on Aging (NIA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Healthy, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00044200, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2018.