VolunteerNCT00397748
PET Scanning of Adults With Attention Deficit Hyperactivity Disorder (ADHD)
An observational study of Volunteer and Attention Deficit Hyperactivity Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 55 years, men only
- Conditions the study is for
- Volunteer, Attention Deficit Hyperactivity Disorder
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Sep 2006to 27 Nov 2012
- 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 55 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- All subjects must have normal values on screening measures to be in the study. They must be male and between 18 and 55 years of age. Primary efforts will also be to recruit non-smokers, given nicotine s ability to release dopamine presynaptically, a confound for this study. Previous smokers who have been abstinent for greater than 1 year may be considered.
Who cannot join
- In addition to psychiatric criteria described above: past or current medical condition that would interfere with brain function - history of alcoholism, tobacco use (must have minimum of one year of full remission/complete abstinence from nicotine), 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; gastrointestinal disorders; abnormal renal, liver or pulmonary function; blood dyscrasias; malignancy; nonstimulant or stimulant pharmacotherapy within 1 month of the study, or any history of antipsychotic medication; neurodegenerative or neurodevelopmental disorder; stroke; epilepsy; sensitivity to flashing lights; subjects requiring regular medication; subjects demonstrated by drug screening to have taken a controlled substance; subjects with a history of hypersensitivity to lidocaine; subjects with IQ less than 80. Females, adolescents and children will be excluded.
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: PET Scanning of Brain Dopaminergic Signal Transduction Involving Arachidonic Acid in Adults With Attention Deficit Hyperactivity Disorder (ADHD)
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.
Read more
Participants undergo the following procedures:
"<TAB>Medical history and psychiatric and medical evaluation, including blood and urine tests.
"<TAB>MRI 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.
"<TAB>PET 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....
Read the detailed description
- 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 A(2) 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.
- 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).
- 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.
- Outcome Parameters
This study has four specific aims. First, regional cerebral blood flow will be quantified in response to an acute challenge with apomorphine s.c. and compared between study groups (ADHD/non-ADHD). Second, dopamine D(2)-like receptor signal transduction will be evaluated by PET in response to an acute challenge with apomorphine s.c. and compared between study groups (ADHD/non-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.
- Keywords
- Phospholipase A2, D2 Receptors, Apomorphine, Trimethobenzamide, Attention Deficit Hyperactivity Disorder, ADHD, Healthy Volunteer, HV
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2006 (estimated)
- Study start15 Sep 2006
- Study completion27 Nov 2012
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 VolunteerStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)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
- Time perspective
- Other
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Investigators
- Judith L Rapoport, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00397748
- Sponsor's protocol ID
- 060246
- Other IDs
- 06-M-0246
- Status last verified
- 27 Nov 2012
- First submitted
- 8 Nov 2006
- Last updated
- 16 Dec 2019
- Results posted
- No
Publications
Agid Y, Pollak P, Bonnet AM, Signoret JL, Lhermitte F. Bromocriptine associated with a peripheral dopamine blocking agent in treatment of Parkinson's disease. Lancet. 1979 Mar 17;1(8116):570-2. doi: 10.1016/s0140-6736(79)91003-1.
PubMed 85162Amenta F, Ricci A, Tayebati SK, Zaccheo D. The peripheral dopaminergic system: morphological analysis, functional and clinical applications. Ital J Anat Embryol. 2002 Jul-Sep;107(3):145-67.
PubMed 12437142Axelrod 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 7537411
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PET Scanning of Brain Dopaminergic Signal Transduction Involving Arachidonic Acid in Adults With Attention Deficit Hyperactivity Disorder (ADHD)
- ClinicalTrials.gov ID
- NCT00397748
- Acronym / sponsor ID
- 060246
- Keywords
- Phospholipase A2, D2 Receptors, Apomorphine, Trimethobenzamide, Attention Deficit Hyperactivity Disorder, ADHD, Healthy Volunteer, HV
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 15 Sep 2006
- Study completion
- 27 Nov 2012
- First posted
- 9 Nov 2006 (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 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:
"<TAB>Medical history and psychiatric and medical evaluation, including blood and urine tests.
"<TAB>MRI 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.
"<TAB>PET 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
- 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 A(2) 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.
- 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).
- 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.
- Outcome Parameters
This study has four specific aims. First, regional cerebral blood flow will be quantified in response to an acute challenge with apomorphine s.c. and compared between study groups (ADHD/non-ADHD). Second, dopamine D(2)-like receptor signal transduction will be evaluated by PET in response to an acute challenge with apomorphine s.c. and compared between study groups (ADHD/non-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 design
- Time perspective
- Other
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- All subjects must have normal values on screening measures to be in the study. They must be male and between 18 and 55 years of age. Primary efforts will also be to recruit non-smokers, given nicotine s ability to release dopamine presynaptically, a confound for this study. Previous smokers who have been abstinent for greater than 1 year may be considered.
Key exclusion criteria (1 listed)
- In addition to psychiatric criteria described above: past or current medical condition that would interfere with brain function - history of alcoholism, tobacco use (must have minimum of one year of full remission/complete abstinence from nicotine), 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; gastrointestinal disorders; abnormal renal, liver or pulmonary function; blood dyscrasias; malignancy; nonstimulant or stimulant pharmacotherapy within 1 month of the study, or any history of antipsychotic medication; neurodegenerative or neurodevelopmental disorder; stroke; epilepsy; sensitivity to flashing lights; subjects requiring regular medication; subjects demonstrated by drug screening to have taken a controlled substance; subjects with a history of hypersensitivity to lidocaine; subjects with IQ less than 80. Females, adolescents and children will be excluded.
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 16 Dec 2019.
- Background: PubMed 85162Agid Y, Pollak P, Bonnet AM, Signoret JL, Lhermitte F. Bromocriptine associated with a peripheral dopamine blocking agent in treatment of Parkinson's disease. Lancet. 1979 Mar 17;1(8116):570-2. doi: 10.1016/s0140-6736(79)91003-1.
- Background: PubMed 12437142Amenta F, Ricci A, Tayebati SK, Zaccheo D. The peripheral dopaminergic system: morphological analysis, functional and clinical applications. Ital J Anat Embryol. 2002 Jul-Sep;107(3):145-67.
- 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.
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Screening Protocol
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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.
Judith L Rapoport, M.D. principal investigator
National Institute of Mental Health (NIMH)
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 Volunteer and Attention Deficit Hyperactivity Disorder, run by National Institute of Mental Health (NIMH) 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 1 inclusion and 1 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 16 Dec 2019. 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 NCT00397748, 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 16 Dec 2019.