Attention Deficit Disorder With Hyperactivity, Conduct Disorder, Substance Abuse
Conditions
Keywords
ADHD, substance abuse risk, Adderall, fMRI, ADHD Treatment, Medication
Brief summary
Childhood ADHD and comorbid oppositional defiant disorder (ODD) and conduct disorder (CD) are considered risk factors for subsequent substance abuse, and youth with both ADHD and ODD/CD are at greatest risk. However, the effects of treatment of ADHD with stimulant medications such as methylphenidate (MPH) and mixed amphetamine salts (MAS) on risk for substance abuse are poorly understood. The study team propose to use fMRI to study the effects of extended release mixed amphetamine salts (MAS-XR) in drug-naïve youth 7-12 years at low risk (i.e., ADHD only) and high risk (i.e., ADHD + ODD/CD) for substance abuse on the brain reward system, to better understand the potential impact of these medications on an aspect of brain functioning which is thought to underlie vulnerability to substance abuse.
Interventions
DRUGAdderall
3 weeks of Adderall
Sponsors
National Institute on Drug Abuse (NIDA)
Jeffrey Newcorn
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
3-week intervention with Adderall as treatment for ADHD among youth with ADHD + Conduct problems. Pre and post fMRI performed as the outcome measures
Eligibility
Sex/Gender
ALL
Age
7 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* General: pre-pubertal (e.g. Tanner stage 1 or 2) * age 7-12 inclusive * signed consent/assent * parent communicates sufficiently in English * Has ADHD as determined by parent interview * ADHD-Rating Scale-5 total score (interview with parent) of 1.5 SD \> age/sex norms * Youth with CD or severe ODD: CD or ODD + 2 symptoms of CD
Exclusion criteria
* major neurological/medical illness * history of head injury * fetal exposure to alcohol/drugs; * diagnosis of major psychiatric disorder (e.g., schizophrenia, bipolar disorder, major depression, generalized anxiety, social phobia, Tourette's Disorder, PTSD, autism spectrum disorder) current suicidal ideation or past history of suicide attempt * Wechsler Abbreviated Scale of Intelligence (WASI) score \<75; 7) * current treatment with stimulants (prior or current treatment with non-stimulants is permitted, but participants must be off medication for 2 weeks at baseline; youth who had a past, brief stimulant medication exposure of no more than about a month, and not within the past 6 months may be included .) * current or past alcohol/drug use (interview; urine toxicology) * psychological or medical condition which precludes being in the scanner (e.g., claustrophobia, morbid obesity) * metal in the body that cannot be removed * visual disturbances that may impair task performance * precocious puberty (e.g. Tanner stage \>2).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in fMRI Measure | baseline and 3 weeks post intervention | Bold activation change within the reward system. The contrasts in blood-oxygenation levels (BOLD) in regions of interest (ROIs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ADHD Rating Score (ADHD RS) | Pretreatment, baseline and Post-Treatment, average 2 weeks | Subscale for Inattention scores range from 0-27, Subscale scores for Hyper (H/I) range from 0-27. The total ADHD score sums to a score of 0-54. Higher indicates more severe ADHD symptomology, and there are norm ranges, with clinical thresholds set at 1.5 SD above the mean for sex and age. |
| Total Dose of MAS-XR | average 2 weeks | Open label trial of MAS XR with flexible dosing and a suggested target of at least 0.5mg/kg |
| Change in Clinical Global Impression - Improvement (CGI-I) | baseline and post treatment, average 2 weeks | The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. Change in CGi post treatment as compared to baseline. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High Risk Children with ADHD and ODD/CD | 11 |
| Low Risk Children with ADHD only | 7 |
| Total | 18 |
Baseline characteristics
| Characteristic | High Risk | Low Risk | Total |
|---|---|---|---|
| Age, Continuous | 9.00 years STANDARD_DEVIATION 1.483 | 10.14 years STANDARD_DEVIATION 1.345 | 9.44 years STANDARD_DEVIATION 1.5 |
| Full Scale IQ (FSIQ) | 102.45 units on a scale STANDARD_DEVIATION 12.003 | 107.29 units on a scale STANDARD_DEVIATION 11.041 | 104.9 units on a scale STANDARD_DEVIATION 11.5 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 7 |
| other Total, other adverse events | 0 / 11 | 0 / 7 |
| serious Total, serious adverse events | 0 / 11 | 0 / 7 |
Outcome results
Primary
Change in fMRI Measure
Bold activation change within the reward system. The contrasts in blood-oxygenation levels (BOLD) in regions of interest (ROIs).
Time frame: baseline and 3 weeks post intervention
Population: Participants who provided imaging data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High Risk | Change in fMRI Measure | Reward Outcome Post-Pre Low>High, Left Amygdala | -0.957100 BOLD signal | Standard Deviation 1.365781 |
| High Risk | Change in fMRI Measure | Reward Outcome Post-Pre Low>High, ACC | -0.139000 BOLD signal | Standard Deviation 1.28847 |
| High Risk | Change in fMRI Measure | Reward Outcome Post-Pre Low>High, Ventral Striatum | 0.853514 BOLD signal | Standard Deviation 0.475767 |
| High Risk | Change in fMRI Measure | Reward Outcome Post-Pre Low>High, Ventrolateral Pre-Frontal Cortex (VLPFC) | 0.712514 BOLD signal | Standard Deviation 0.944126 |
| Low Risk | Change in fMRI Measure | Reward Outcome Post-Pre Low>High, Ventrolateral Pre-Frontal Cortex (VLPFC) | 0.460432 BOLD signal | Standard Deviation 0.744686 |
| Low Risk | Change in fMRI Measure | Reward Outcome Post-Pre Low>High, Left Amygdala | 0.572517 BOLD signal | Standard Deviation 0.71241 |
| Low Risk | Change in fMRI Measure | Reward Outcome Post-Pre Low>High, Ventral Striatum | -0.321983 BOLD signal | Standard Deviation 1.075986504 |
| Low Risk | Change in fMRI Measure | Reward Outcome Post-Pre Low>High, ACC | 1.876717 BOLD signal | Standard Deviation 1.615755 |
Secondary
ADHD Rating Score (ADHD RS)
Subscale for Inattention scores range from 0-27, Subscale scores for Hyper (H/I) range from 0-27. The total ADHD score sums to a score of 0-54. Higher indicates more severe ADHD symptomology, and there are norm ranges, with clinical thresholds set at 1.5 SD above the mean for sex and age.
Time frame: Pretreatment, baseline and Post-Treatment, average 2 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| High Risk | ADHD Rating Score (ADHD RS) | ADHRS-total baseline | 43.18 score on a scale | Standard Deviation 7.264 |
| High Risk | ADHD Rating Score (ADHD RS) | ADHRS-total post Tx | 20.36 score on a scale | Standard Deviation 13.677 |
| High Risk | ADHD Rating Score (ADHD RS) | ADHRS-hyper baseline | 20.55 score on a scale | Standard Deviation 5.298 |
| High Risk | ADHD Rating Score (ADHD RS) | ADHRS-hyper post Tx | 10.09 score on a scale | Standard Deviation 7.355 |
| High Risk | ADHD Rating Score (ADHD RS) | ADHRS-InAtt baseline | 22.64 score on a scale | Standard Deviation 3.906 |
| High Risk | ADHD Rating Score (ADHD RS) | ADHRS- InAtt post Tx | 10.27 score on a scale | Standard Deviation 7.016 |
| Low Risk | ADHD Rating Score (ADHD RS) | ADHRS-InAtt baseline | 20.14 score on a scale | Standard Deviation 7.988 |
| Low Risk | ADHD Rating Score (ADHD RS) | ADHRS-total baseline | 39.86 score on a scale | Standard Deviation 13.057 |
| Low Risk | ADHD Rating Score (ADHD RS) | ADHRS-hyper post Tx | 8.86 score on a scale | Standard Deviation 3.805 |
| Low Risk | ADHD Rating Score (ADHD RS) | ADHRS-total post Tx | 12.71 score on a scale | Standard Deviation 5.314 |
| Low Risk | ADHD Rating Score (ADHD RS) | ADHRS- InAtt post Tx | 8.86 score on a scale | Standard Deviation 3.805 |
| Low Risk | ADHD Rating Score (ADHD RS) | ADHRS-hyper baseline | 19.71 score on a scale | Standard Deviation 6.651 |
Secondary
Change in Clinical Global Impression - Improvement (CGI-I)
The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. Change in CGi post treatment as compared to baseline.
Time frame: baseline and post treatment, average 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Risk | Change in Clinical Global Impression - Improvement (CGI-I) | 2.0 score on a scale | Standard Deviation 0.632 |
| Low Risk | Change in Clinical Global Impression - Improvement (CGI-I) | 2.00 score on a scale | Standard Deviation 0.577 |
Secondary
Total Dose of MAS-XR
Open label trial of MAS XR with flexible dosing and a suggested target of at least 0.5mg/kg
Time frame: average 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Risk | Total Dose of MAS-XR | 1487.09 mg | Standard Deviation 2108.303 |
| Low Risk | Total Dose of MAS-XR | 745.00 mg | Standard Deviation 594.636 |