Attention Deficit Hyperactivity Disorder
Conditions
Keywords
Brookhaven, ADHD, Dopamine, methylphenidate, PET
Brief summary
The purpose of the study is to investigate the functional state of dopamine cells and the dopamine transporter in ADHD subjects and controls to assess the effects of chronic methylphenidate treatment on dopamine cell function and dopamine transporter levels in ADHD subjects.
Interventions
DRUGExperimental: methylphenidate treatment
subjects received mehtylphenidate treatment for 12 months
Sponsors
Icahn School of Medicine at Mount Sinai
Duke University
University of California, Irvine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Must give informed consent * Must be between the ages of 18 and 45 years old. * Must have a confirmed diagnosis of ADHD * Must have scored on a rating scale that indicate a significant level of symptom severity. * Must have a childhood history of ADHD must be documented using established test criteria. * Must have had no previous medication treatment for ADHD except for a short term treatment period of less than three months, which should have occurred at least six months prior to the study. * Must have an interest in receiving long-term medication treatment for ADHD.
Exclusion criteria
* Must not test positive for psychoactive drugs during a urine drug screen. * Must not be pregnant. * Must not be breastfeeding. * Must have no past or present history of dependence on alcohol or other drugs of abuse except nicotine or caffeine. * Must have no past or present history of a psychiatric disorder except ADHD. * Must have no medical illness that may affect brain function. * Must not have taken medication that may affect brain function. * Must not have had head trauma with loss of consciousness (\> 30 minutes). * Must not have significant anxiety or depression as determined by an established test. * Must have no history of a significant learning disability. * Must have no history of cardiovascular or endocrinological disease. * Must have no history of coagulation disorder. * Must have no history of sensitivity to lidocaine and/or prilocaine. * Must have no history of claustrophobia. * Contraindication to MRI environment (presence of any implanted metallic objects such as cardiac/neural pacemakers, defibrillators, aneurysm clips, certain heart valves, spinal nerve stimulators, artificial joints/limbs, shrapnel/bullets, metal fragments in their eyes, cochlear implants, hearing aids, dental implants). * Must have no history of glaucoma.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DAT Availability | 1 year | Striatal DAT availability as noted in PET scans post one year of methylphenidate treatment or no intervention. The unit listed as binding potential (BPND) was measured with a dynamic PET scan protocol, using carbon-11 labeled cocaine, a radioligand with specific binding to DAT (which is inhibited by drugs that block DAT but not by drugs that block the norephephrine or serotonin transporters). This radiotracer was utilized to quantify DAT availability as non-displaceable binding potential using a standard kinetic model for reversible ligands. The dynamic PET scans were started immediately after injection of \[11C\]cocaine (specific activity 0.5-1.5 Ci/uM at end of bombardment). Arterial blood was obtained to measure the concentration of unchanged \[11C\] cocaine in plasma for quantification of DAT availability. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited at 3 sites from 2004 - 2008. They were all consented to the protocol before any study procedures were done.Subjects were recruited through flyers and newspaper ads. They were seen at medical clinics and ADHD diagnosis was confirmed. All subjects were treatment naive for stimulant medications.
Pre-assignment details
Subjects were interviewed to determine mental health diagnosis of ADHD with symptoms existing since childhood. All other psychiatric diagnoses were exclusionary as was neurological or cerebral disease. Healthy controls were also recruited. All subjects were then scheduled for scans at Brookhaven and ADHD subjects then recieved one year of meds.
Participants by arm
| Arm | Count |
|---|---|
| Methylphenidate Treatment methylphenidate treatment
methylphenidate : Subjects (18) in this arm recieved methylphenidate for one year. | 55 |
| no Intervention no intervention for 12 months
no intervention : no treatment for 11 subjects for 12 months | 20 |
| Total | 75 |
Baseline characteristics
| Characteristic | Methylphenidate Treatment | no Intervention | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 55 Participants | 20 Participants | 75 Participants |
| Age, Continuous | 30.9 years STANDARD_DEVIATION 1.9 | 33.2 years STANDARD_DEVIATION 1.6 | 31.5 years STANDARD_DEVIATION 1.5 |
| PET scan of DAT availability | 55 participants | 20 participants | 75 participants |
| Region of Enrollment United States | 55 participants | 20 participants | 75 participants |
| Sex: Female, Male Female | 30 Participants | 12 Participants | 42 Participants |
| Sex: Female, Male Male | 25 Participants | 8 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 20 |
| other Total, other adverse events | 0 / 55 | 0 / 20 |
| serious Total, serious adverse events | 0 / 55 | 0 / 20 |
Outcome results
Primary
DAT Availability
Striatal DAT availability as noted in PET scans post one year of methylphenidate treatment or no intervention. The unit listed as binding potential (BPND) was measured with a dynamic PET scan protocol, using carbon-11 labeled cocaine, a radioligand with specific binding to DAT (which is inhibited by drugs that block DAT but not by drugs that block the norephephrine or serotonin transporters). This radiotracer was utilized to quantify DAT availability as non-displaceable binding potential using a standard kinetic model for reversible ligands. The dynamic PET scans were started immediately after injection of \[11C\]cocaine (specific activity 0.5-1.5 Ci/uM at end of bombardment). Arterial blood was obtained to measure the concentration of unchanged \[11C\] cocaine in plasma for quantification of DAT availability.
Time frame: 1 year
Population: DAT availability was measured as ratio of distribution volume in striatum to cerebellum -1 (BPND-1), which represents number of transporters free to bind radiotracer. Distribution volume ratio images were transformed into images by computing total distribution volume in each pixel and dividing by distribution volume in cerebellum. Regions of interest in striatum (caudate, putamen, ventral striatum) were drawn on an averaged emission image (10 to 60 minutes for \[11C\] cocaine).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methylphenidate Treatment | DAT Availability | 2.68 ratio | Standard Deviation 0.28 |
| no Intervention | DAT Availability | 2.85 ratio | Standard Deviation 0.31 |