Ignite Creation Date:
2024-05-05 @ 5:09 PM
Last Modification Date:
2024-10-26 @ 9:28 AM
Study NCT ID:
NCT00397748
Status:
COMPLETED
Last Update Posted:
2019-12-16
First Post:
2006-11-08
Brief Title:
PET Scanning of Adults With Attention Deficit Hyperactivity Disorder ADHD
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
PET Scanning of Brain Dopaminergic Signal Transduction Involving Arachidonic Acid in Adults With Attention Deficit Hyperactivity Disorder ADHD
Status:
COMPLETED
Status Verified Date:
2012-11-27
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will explore the brain in men with and without attention deficit hyperactivity disorder ADHD It will use positron emission tomography PET and magnetic resonance imaging MRI to study brain function and nerve cell communication involving phospholipids fatty molecules that make up the covering of nerve cell fibers in the brain and are involved in communication between the cells It will also look at how nerve cell communication is related to blood flow In particular the study will explore communication through the dopamine system which is one of the main neurotransmitter systems in the brain involved in ADHD
Healthy men and men with ADHD between 18 and 55 years of age may be eligible for this study
Participants undergo the following procedures
TABMedical history and psychiatric and medical evaluation including blood and urine tests
TABMRI scan This test uses a strong magnetic field and radio waves to obtain images of the brain The subject lies still on a table that slides into the scanner a metal cylinder during the scanning
TABPET scanning The subject lies on the scanner bed with his head held still using a special facemask A catheter plastic tube or needle is placed in an artery to collect blood samples and in a vein to inject radioactive isotopes for measuring blood flow and phospholipid metabolism Scans are done after an injection of a saline solution and again after injection of apomorphine a medication that turns on dopamine receptors in the brain The injections are given under the skin of the abdomen about one and a half hours apart
Healthy men and men with ADHD between 18 and 55 years of age may be eligible for this study
Participants undergo the following procedures
TABMedical history and psychiatric and medical evaluation including blood and urine tests
TABMRI scan This test uses a strong magnetic field and radio waves to obtain images of the brain The subject lies still on a table that slides into the scanner a metal cylinder during the scanning
TABPET scanning The subject lies on the scanner bed with his head held still using a special facemask A catheter plastic tube or needle is placed in an artery to collect blood samples and in a vein to inject radioactive isotopes for measuring blood flow and phospholipid metabolism Scans are done after an injection of a saline solution and again after injection of apomorphine a medication that turns on dopamine receptors in the brain The injections are given under the skin of the abdomen about one and a half hours apart
Detailed Description:
A Objective
Attention deficit hyperactivity disorder ADHD is a heritable neurodevelopmental disorder with a reported male predominance that persists into adulthood and leads to significant morbidity in affected individuals ADHD is currently hypothesized to reflect central dopaminergic dysfunction Evaluation of human dopaminergic dysfunction using in vivo neuroimaging has been limited to studies of receptor localization and quantification and dopamine synthesis rather than direct measurement of the functional status of receptor signaling There exists a need to thoroughly elucidate mechanisms underlying aberrant dopaminergic neurotransmission downstream of receptor activation in signaling processes We have developed an in vivo method to measure neuroreceptor-initiated signal transduction involving activation of phospholipase A2 to release the second messenger arachidonic acid AA We propose to use positron emission tomography PET to quantitatively image dopamine-initiated signal transduction via AA in ADHD patients and healthy volunteers in subjects administered the dopaminergic agonist apomorphine and to measure regional cerebral blood flow rCBF as well We hypothesize that signaling and flow responses to apomorphine will be elevated demonstrating hypersensitivity of the dopamine signaling mechanism
B Study population
18 healthy male volunteers between the ages of 18 and 55 will be recruited for this study see justification for recruitment of males only in Study Design and Methods
C Design
All subjects will have up to four study-related visits to the Clinical Center in Bethesda over a one-year period including an overnight stay Participants will also be asked to complete an initial comprehensive telephone questionnaire to elicit whether they meet criteria for study participation followed by on-site visits to NIH to complete a modified battery of neuropsychiatric screening tests related to symptom presence and severity Questions relating to medical family psychiatric and developmental histories and lifestyle will be asked In addition visits will include a physical exam as well as blood and urine collection and structural magnetic resonance imaging MRI of the head Subject participation will culminate with sequential subcutaneous administration of a single dose of control vehicle solution control followed by the dopamine agonist apomorphine after appropriate pre-medication with the anti-emetic trimethobenzamide or two sequential injections of vehicle for PET scans with attendant radiolabeled compounds
D Outcome Parameters
This study has four specific aims First regional cerebral blood flow will be quantified in response to an acute challenge with apomorphine sc and compared between study groups ADHDnon-ADHD Second dopamine D2-like receptor signal transduction will be evaluated by PET in response to an acute challenge with apomorphine sc and compared between study groups ADHDnon-ADHD Third baseline esterified and unesterified serum fatty acids will be compared between patients and control subjects Lastly we will examine the acute effect of apomorphine in the stimulation of serum growth hormone in all subjects as confirmatory evidence for stimulation of central dopaminergic receptors
Attention deficit hyperactivity disorder ADHD is a heritable neurodevelopmental disorder with a reported male predominance that persists into adulthood and leads to significant morbidity in affected individuals ADHD is currently hypothesized to reflect central dopaminergic dysfunction Evaluation of human dopaminergic dysfunction using in vivo neuroimaging has been limited to studies of receptor localization and quantification and dopamine synthesis rather than direct measurement of the functional status of receptor signaling There exists a need to thoroughly elucidate mechanisms underlying aberrant dopaminergic neurotransmission downstream of receptor activation in signaling processes We have developed an in vivo method to measure neuroreceptor-initiated signal transduction involving activation of phospholipase A2 to release the second messenger arachidonic acid AA We propose to use positron emission tomography PET to quantitatively image dopamine-initiated signal transduction via AA in ADHD patients and healthy volunteers in subjects administered the dopaminergic agonist apomorphine and to measure regional cerebral blood flow rCBF as well We hypothesize that signaling and flow responses to apomorphine will be elevated demonstrating hypersensitivity of the dopamine signaling mechanism
B Study population
18 healthy male volunteers between the ages of 18 and 55 will be recruited for this study see justification for recruitment of males only in Study Design and Methods
C Design
All subjects will have up to four study-related visits to the Clinical Center in Bethesda over a one-year period including an overnight stay Participants will also be asked to complete an initial comprehensive telephone questionnaire to elicit whether they meet criteria for study participation followed by on-site visits to NIH to complete a modified battery of neuropsychiatric screening tests related to symptom presence and severity Questions relating to medical family psychiatric and developmental histories and lifestyle will be asked In addition visits will include a physical exam as well as blood and urine collection and structural magnetic resonance imaging MRI of the head Subject participation will culminate with sequential subcutaneous administration of a single dose of control vehicle solution control followed by the dopamine agonist apomorphine after appropriate pre-medication with the anti-emetic trimethobenzamide or two sequential injections of vehicle for PET scans with attendant radiolabeled compounds
D Outcome Parameters
This study has four specific aims First regional cerebral blood flow will be quantified in response to an acute challenge with apomorphine sc and compared between study groups ADHDnon-ADHD Second dopamine D2-like receptor signal transduction will be evaluated by PET in response to an acute challenge with apomorphine sc and compared between study groups ADHDnon-ADHD Third baseline esterified and unesterified serum fatty acids will be compared between patients and control subjects Lastly we will examine the acute effect of apomorphine in the stimulation of serum growth hormone in all subjects as confirmatory evidence for stimulation of central dopaminergic receptors
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 06-M-0246 | None | None | None |