ADHD
Conditions
Keywords
HMRS Scanning, ADHD, Child, Adolescent, HMRS Scans
Brief summary
This will be an open label study using daily does of up to 126mg/day of Concerta in the treatment of children and adolescents, ages 12-17, who meet DSM-IV criteria for ADHD. Specific hypotheses are as follows: Hypothesis 1: Children and adolescents with ADHD will have significantly higher ACC and DLPFC Glutamate/myo-Inositol containing compounds (Glu/Ino) and Glutamate/creatine + phosphocreatine (Glu/Cr) than matched HCS. Hypothesis 2: After six weeks of treatment, OROS methylphenidate will lower ACC and DLPFC Glu/Ino and Glu/Cr levels in children with ADHD who are methylphenidate responders.
Detailed description
The primary objective of this study is to use 1H MRS to assess Glutamate (Glu), myo-Inositol (Ino), and creatine + phosphocreatine (Cr) levels in brain regions of interest in 20 children with ADHD between the ages of 12-17 years old, before and after a six-week open treatment trial with OROS methylphenidate. For comparison, 1H MRS will also be obtained from 20 controls matched by age and gender. We also will scan 20 children with ADHD between the ages of 12-17 years old that are currently enrolled in the protocol entitled Prevention of Cigarette Smoking in ADHD Youth with Concerta (2003-P-001313) and on a stable dose of Concerta. These 20 children will be scanned once while on medication and once while off medication
Interventions
Concerta is given in capsule form with a minimum dose of 18 mg/day and a max of 126 mg/day. Subjects take Concerta once per day for 6 weeks.
OTHERNo intervention
No intervention
Sponsors
Massachusetts General Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 18 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or female subjects, 12-17 years of age. 2. ADHD subjects must meet study criteria for the Prevention of Cigarette Smoking in ADHD Youth with CONCERTA Protocol; #2003-P-001313. 3. Control subjects must not meet full DSM-IV criteria for Attention Deficit Hyperactivity Disorder, or any other current major psychiatric disorder. 4. Each subject and his/her authorized legal representative must understand the nature of this proposed study, and must sign informed consent and informed assent documents. 5. Subject and parent must have a level of understanding sufficient to communicate intelligently with the investigator and study coordinator, and to cooperate with study procedures.
Exclusion criteria
1. Clinically significant chronic medical condition including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease. 2. Organic brain disorders or mental retardation (I.Q. \<75). 3. Contraindication to MRI including presence of metal or surgical devices (plates, implants, braces or other items). 4. Pregnancy; women of child bearing potential must be using a medically approved method of birth control. Women of child bearing potential will receive a urinary pregnancy test prior to each MR scanning session. 5. Severe phobia of being in small, enclosed spaces. 6. Investigator and his/her immediate family; defined as the investigator's spouse, parent, child, grandparent, or grandchild will not be eligible to participate in the treatment arm of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proton Magnetic Resonance Spectroscopy (H MRS) Scan Results - Glutamate(Glu)/Myo-inositol-containing Compounds (Ino) | after 6 weeks Concerta treatment | Comparison of treated ADHD participants (6 weeks on Concerta) and Healthy Control Subjects (HCS) This measure is a ratio of Glutamate (excitatory neurotransmitter) to myo-inositol (cyclic sugar alcohol) containing compounds in the anterior cingulate. |
| H MRS Scan Results - Glutamine (Gln)/Ino | after 6 weeks Concerta treatment | Comparison of treated ADHD participants (6 weeks on Concerta) and Healthy Control Subjects (HCS) This measure is a ratio of Glutamine (amino acid precursor to Glu) to myo-inositol (cyclic sugar alcohol) containing compounds in the anterior cingulate. |
| H MRS Scan Results - Glutamate & Glutamine (Glx)/Ino | after 6 weeks Concerta treatment | Comparison of treated ADHD participants (6 weeks on Concerta) and Healthy Control Subjects (HCS) This measure is a ratio of Glutamate and it's precursor, Glutamine, to myo-inositol (cyclic sugar alcohol) containing compounds in the anterior cingulate. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| OROS Methylphenidate OROS = Osmotic-controlled Release Oral delivery System | 27 |
| Control Healthy Volunteer Control group | 12 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal Scan | 1 | 0 |
| Overall Study | Scan Anxiety | 3 | 0 |
| Overall Study | Unreadable Scan | 1 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 0 |
Baseline characteristics
| Characteristic | OROS Methylphenidate | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 27 Participants | 12 Participants | 39 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 27 participants | 12 participants | 39 participants |
| Sex: Female, Male Female | 9 Participants | 5 Participants | 14 Participants |
| Sex: Female, Male Male | 18 Participants | 7 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 27 | 0 / 12 |
| serious Total, serious adverse events | 0 / 27 | 0 / 12 |
Outcome results
Primary
H MRS Scan Results - Glutamate & Glutamine (Glx)/Ino
Comparison of treated ADHD participants (6 weeks on Concerta) and Healthy Control Subjects (HCS) This measure is a ratio of Glutamate and it's precursor, Glutamine, to myo-inositol (cyclic sugar alcohol) containing compounds in the anterior cingulate.
Time frame: after 6 weeks Concerta treatment
Population: Seven subjects who completed the protocol were not included due to a lack of baseline comparison.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OROS Methylphenidate | H MRS Scan Results - Glutamate & Glutamine (Glx)/Ino | 2.58 MRS Ratio | Standard Deviation 0.73 |
| Control | H MRS Scan Results - Glutamate & Glutamine (Glx)/Ino | 2.59 MRS Ratio | Standard Deviation 0.87 |
Primary
H MRS Scan Results - Glutamine (Gln)/Ino
Comparison of treated ADHD participants (6 weeks on Concerta) and Healthy Control Subjects (HCS) This measure is a ratio of Glutamine (amino acid precursor to Glu) to myo-inositol (cyclic sugar alcohol) containing compounds in the anterior cingulate.
Time frame: after 6 weeks Concerta treatment
Population: Seven subjects who completed the protocol were not included due to a lack of baseline comparison.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OROS Methylphenidate | H MRS Scan Results - Glutamine (Gln)/Ino | 1.08 MRS Ratios | Standard Deviation 0.43 |
| Control | H MRS Scan Results - Glutamine (Gln)/Ino | 1.02 MRS Ratios | Standard Deviation 0.6 |
Primary
Proton Magnetic Resonance Spectroscopy (H MRS) Scan Results - Glutamate(Glu)/Myo-inositol-containing Compounds (Ino)
Comparison of treated ADHD participants (6 weeks on Concerta) and Healthy Control Subjects (HCS) This measure is a ratio of Glutamate (excitatory neurotransmitter) to myo-inositol (cyclic sugar alcohol) containing compounds in the anterior cingulate.
Time frame: after 6 weeks Concerta treatment
Population: Seven subjects who completed the protocol were not included due to a lack of baseline comparison.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OROS Methylphenidate | Proton Magnetic Resonance Spectroscopy (H MRS) Scan Results - Glutamate(Glu)/Myo-inositol-containing Compounds (Ino) | 1.50 MRS Ratio | Standard Deviation 0.45 |
| Control | Proton Magnetic Resonance Spectroscopy (H MRS) Scan Results - Glutamate(Glu)/Myo-inositol-containing Compounds (Ino) | 1.56 MRS Ratio | Standard Deviation 0.34 |