Attention Deficit Hyperactivity Disorder
Conditions
Keywords
ADHD, Vyvanse, stimulant medication, ADD
Brief summary
The aim of this study is to examine the mechanisms by which stimulant medications reduce symptoms in patients with Attention Deficit Hyperactivity Disorder (ADHD). Using Magnetic Resonance Imaging (MRI), the investigators have found that the volumes of certain brain regions are reduced in patients with ADHD. The reduced volumes were much less pronounced if patients had been treated with stimulant medications, suggesting that stimulants may reduce the symptoms of ADHD by reversing these volume reductions. In a second and related study, the investigators found that in patients with ADHD, emotional processing was normalized when patients were taking stimulant medications. Both studies point to possible mechanisms by which stimulants are effective; however, a significant limitation of these findings is that they were derived from cross-sectional studies. In this current study, the investigators hope to replicate these treatment effects of stimulants in a prospective, controlled manner. The investigators plan to measure ADHD symptom severity in patients before and after 12-weeks of controlled treatment with either a stimulant medication or placebo while utilizing structural and functional MRI. Combining imaging with a randomized controlled trial will allow us to better assess the effects of stimulants on brain function and structure.
Detailed description
A cohort of 100 patients with ADHD will be recruited for a 12 week, double-blind, parallel, randomized controlled trial of Lisdexamfetamine (Vyvanse) versus placebo, with 50 patients randomized to Lisdexamfetamine and the other 50 patients to placebo. The investigators will acquire high-resolution, anatomical and functional MRI images at baseline and after 12 weeks of treatment. In addition, 75 age- and sex-matched healthy control subjects will be imaged at baseline.
Interventions
DRUGLisdexamfetamine
During the first 4 weeks of treatment, the dosage of Lisdexamfetamine will be adjusted based on the patient's response to the medication. The patient will then be maintained at the lowest effective dose for the remaining 8 weeks of treatment.
DRUGPlacebo
Placebo dosing will parallel that of Lisdexamfetamine.
Sponsors
Shire
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Two treatment arms plus sample of healthy controls, who were assessed at one time point
Eligibility
Sex/Gender
ALL
Age
6 Years to 25 Years
Healthy volunteers
Yes
Inclusion criteria
ADHD Participants: Meets Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria for a primary diagnosis of ADHD, any subtype. Healthy Control Participants: No current DSM-IV-TR Axis I psychiatric diagnosis. All Participants: 1. Male or female, 6 - 25 years of age, and in good physical health 2. English-speaking
Exclusion criteria
1. Current comorbid DSM-IV-TR Axis I psychiatric diagnosis or other symptomatic manifestations that, in the opinion of the examining physician, will contraindicate Lisdexamfetamine treatment or confound safety assessments 2. Meets DSM-IV-TR criteria for active substance abuse and/or dependence 3. Lifetime history of cocaine or stimulant abuse or dependence 4. Actively suicidal 5. Children and adolescents: Prior treatment with psychostimulants for longer than 1 month duration and/or treatment with psychostimulants within the past 4 months Adults: Treatment with psychostimulants within the past 12 months. 6. Documented allergy or intolerance to Lisdexamfetamine or other stimulant medications. 7. Taking other medications with central nervous system effects. 8. History of seizure (other than febrile seizure) 9. Diagnosis of hyperthyroidism, glaucoma, or other serious medical illness. 10. Personal or family history of medical conditions, such as cardiovascular disease, that may interfere with study participation, or for which treatment with Lisdexamfetamine may pose a risk 11. Pregnant or lactating 12. MRI contraindications such as pacemaker, braces, etc. 13. Full scale intelligence quotient (FSIQ) less than 70
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain Structure Volume | 12 weeks | Brain structure volume measured in mm\^3 |
Countries
United States
Participant flow
Recruitment details
Recruitment started in 2011 and ended in 2018. Participants were primarily recruited from the community through advertisements in local newspapers and flyers posted in local establishments. Participants were also recruited from other research studies and doctor's offices.
Pre-assignment details
18 ADHD participants withdrew or were excluded from the study prior to randomization and thus are not included. Participants who withdrew were no longer interested in treatment or were lost to follow-up. Participants were excluded due to subthreshold ADHD symptoms, comorbid psychiatric conditions, & MRI contraindications.
Participants by arm
| Arm | Count |
|---|---|
| Healthy Control Baseline evaluation only | 37 |
| ADHD - Placebo ADHD participants randomized to receive placebo for 12 weeks of treatment | 28 |
| ADHD - Vyvanse ADHD participants randomized to receive 12 weeks of medication treatment with Vyvanse | 27 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 2 |
| Overall Study | Physician Decision | 3 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Healthy Control | Total | ADHD - Vyvanse | ADHD - Placebo |
|---|---|---|---|---|
| Age, Continuous | 16.54 years STANDARD_DEVIATION 6.03 | 14.16 years STANDARD_DEVIATION 6.15 | 12.85 years STANDARD_DEVIATION 5.68 | 11.93 years STANDARD_DEVIATION 5.72 |
| Brain Structure Volume Left Amygdala Volume | 1504.81 mm^3 STANDARD_DEVIATION 217.54 | 1475.62 mm^3 STANDARD_DEVIATION 218.31 | 1489.02 mm^3 STANDARD_DEVIATION 235.93 | 1423.08 mm^3 STANDARD_DEVIATION 199.23 |
| Brain Structure Volume Left Hippocampal Volume | 4182.87 mm^3 STANDARD_DEVIATION 418.83 | 4090.25 mm^3 STANDARD_DEVIATION 424.92 | 4121.96 mm^3 STANDARD_DEVIATION 392.76 | 3933.96 mm^3 STANDARD_DEVIATION 433.45 |
| Brain Structure Volume Right Amygdala Volume | 1695.09 mm^3 STANDARD_DEVIATION 187.81 | 1651.16 mm^3 STANDARD_DEVIATION 210.79 | 1665.87 mm^3 STANDARD_DEVIATION 234.17 | 1577.34 mm^3 STANDARD_DEVIATION 204.15 |
| Brain Structure Volume Right Hippocampal Volume | 4288.01 mm^3 STANDARD_DEVIATION 358.26 | 4174.96 mm^3 STANDARD_DEVIATION 395.07 | 4185.40 mm^3 STANDARD_DEVIATION 379.97 | 4011.48 mm^3 STANDARD_DEVIATION 413.65 |
| Race/Ethnicity, Customized Race/Ethnicity American Indian/Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Asian or Pacific Islander | 1 Participants | 6 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Black or African American | 6 Participants | 21 Participants | 4 Participants | 11 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Hispanic | 7 Participants | 24 Participants | 10 Participants | 7 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Other or Unknown | 2 Participants | 5 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Race/Ethnicity White | 21 Participants | 36 Participants | 9 Participants | 6 Participants |
| Sex: Female, Male Female | 15 Participants | 33 Participants | 9 Participants | 9 Participants |
| Sex: Female, Male Male | 22 Participants | 59 Participants | 18 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 29 | 0 / 29 |
| other Total, other adverse events | 0 / 41 | 0 / 29 | 0 / 29 |
| serious Total, serious adverse events | 0 / 41 | 0 / 29 | 0 / 29 |
Outcome results
Primary
Brain Structure Volume
Brain structure volume measured in mm\^3
Time frame: 12 weeks
Population: ADHD participants who completed 12 weeks of treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ADHD - Placebo | Brain Structure Volume | Left Hippocampal Volume | 3909.85 mm^3 | Standard Deviation 535.35 |
| ADHD - Placebo | Brain Structure Volume | Left Amygdala Volume | 1431.31 mm^3 | Standard Deviation 245.4 |
| ADHD - Placebo | Brain Structure Volume | Right Hippocampal Volume | 4048.10 mm^3 | Standard Deviation 454.37 |
| ADHD - Placebo | Brain Structure Volume | Right Amygdala Volume | 1573.57 mm^3 | Standard Deviation 240.03 |
| ADHD - Vyvanse | Brain Structure Volume | Right Amygdala Volume | 1641.88 mm^3 | Standard Deviation 207.45 |
| ADHD - Vyvanse | Brain Structure Volume | Left Hippocampal Volume | 4069.72 mm^3 | Standard Deviation 426.46 |
| ADHD - Vyvanse | Brain Structure Volume | Right Hippocampal Volume | 4206.41 mm^3 | Standard Deviation 413.38 |
| ADHD - Vyvanse | Brain Structure Volume | Left Amygdala Volume | 1485.05 mm^3 | Standard Deviation 235.17 |