Attention Deficit Hyperactivity Disorder
Conditions
Keywords
ADHD, Intuniv, Non-stimulant, Guanfacine extended-release, Vyvanse, Stimulant, Lisdexamfetamine
Brief summary
Children with Attention-Deficit/Hyperactivity Disorder (ADHD) are typically treated with two types of medications with differing mechanisms of action: stimulants and non-stimulants. The stimulant Vyvanse (lisdexamfetamine, LDX), and the non-stimulant Intuniv (extended-release guanfacine, GXR), are both FDA approved treatment for ADHD. Clinical trials have shown that both medications are effective in reducing ADHD symptoms, although the neurobiological mechanisms by which Vyvanse and Intuniv produce these effects remain unknown. The aim of this study is to examine the mechanisms by which LDX and GXR reduce symptoms in patients with ADHD. MRI scanning will be used to identify treatment-related changes in brain structure and function.
Detailed description
Children with ADHD and age and sex-matched healthy controls will be scanned at the beginning of the study. In this first part of the study, MRI findings will be compared between the two groups to see whether brain functioning of children with ADHD differs from that of healthy children. In the second part of the study, the children with ADHD will meet weekly with the study doctor and be administered either extended-release guanfacine (Intuniv) or lisdexamfetamine (Vyvanse) for 6 weeks. Selection into either treatment group will be randomly determined. At the end of the study, the children with ADHD treated with either medication will have a second MRI scan. The findings of that second MRI scan will be compared to the first MRI scan in order to examine brain changes due to the medication. These second MRI scans will also be compared to the scans of the healthy controls.
Interventions
DRUGGuanfacine
Participants will meet with the study doctor on a weekly basis during the treatment phase of the study. In the first few weeks, the daily dose of the medication will be individually adjusted by the study doctor according to participants' clinical response to and tolerability of the medication. The optimal dose will then be maintained for the remainder of the treatment period.
DRUGLisdexamfetamine
Participants will meet with the study doctor on a weekly basis during the treatment phase of the study. In the first few weeks, the daily dose of the medication will be individually adjusted by the study doctor according to participants' clinical response to and tolerability of the medication. The optimal dose will then be maintained for the remainder of the treatment period.
Sponsors
Columbia University
American Academy of Child Adolescent Psychiatry.
Shire
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
Yes
Inclusion criteria
ADHD Participants: * The participant satisfies Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for a primary diagnosis of ADHD, any subtype. Healthy Control Participants: * The participant must have no current DSM Axis I psychiatric disorder. All Participants: * Participants must provide assent and a legal guardian must provide consent. * The participant is male or female and between 6 - 17 years of age and in good physical health. * Girls of childbearing potential must have a negative urine pregnancy test and, if sexually active, must be using adequate contraception. * The participant is English speaking.
Exclusion criteria
ADHD Participants: * The participant has a current comorbid DSM Axis I psychiatric diagnosis or other symptomatic manifestations that, in the opinion of the study doctor, will contraindicate lisdexamfetamine or guanfacine treatment or confound safety assessments. * The participant meets DSM-5 criteria for current substance abuse and/or dependence. * The participant is currently taking or has taken within the past 4 months, a psychotropic medication. * The participant has a documented allergy or intolerance to lisdexamfetamine or guanfacine products. * The participant has a diagnosis or a history of cardiovascular disease or any other serious medical illness. * The participant is pregnant or lactating. * The participant is actively suicidal. * MRI contraindications (e.g., irremovable metal on the body, pacemaker, braces) * The participant has a full-scale intelligence quotient (IQ) less than 70. * The participant has a history of seizure (except febrile seizure). Healthy Controls: * The participant meets DSM criteria for current substance abuse and/or dependence. * The participant is currently taking a psychotropic medication. * The participant has a history of a serious medical illness. * The participant is pregnant or lactating. * MRI contraindications (e.g., irremovable metal on the body, pacemaker, braces) * The participant has a full-scale intelligence quotient (IQ) less than 70. * The participant has a history of seizure (except febrile seizure).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Brain Segmentation Volume Produced by Stimulant or Non-stimulant Medications in Patients With ADHD | Baseline and 6 weeks | Brain segmentation volume measured in mm\^3. We are reporting the mean difference in brain segmentation volume from baseline (pre-test) to 6 weeks (post-test). No statistical analysis information is being submitted for the affected outcome measure. No statistical analyses have been performed or would be considered scientifically appropriate because actual enrollment fell well below target enrollment. Enrollment terminated early as a result of the COVID-19 pandemic. |
Countries
United States
Participant flow
Recruitment details
Recruitment started in 2014 and ended in 2020. 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
5 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 |
|---|---|
| ADHD - Guanfacine ADHD participants who were randomized to receive guanfacine for 6 weeks of treatment | 5 |
| ADHD - Lisdexamfetamine ADHD participants who were randomized to receive lisdexamfetamine for 6 weeks of treatment | 4 |
| Healthy Controls Age- and sex- matched healthy control participants; baseline procedures only | 15 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Psychiatric diagnosis (e.g., ADHD, MDD) | 0 | 0 | 6 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 3 |
Baseline characteristics
| Characteristic | ADHD - Guanfacine | ADHD - Lisdexamfetamine | Healthy Controls | Total |
|---|---|---|---|---|
| Age, Continuous | 10 years STANDARD_DEVIATION 2.35 | 8.75 years STANDARD_DEVIATION 0.96 | 9.6 years STANDARD_DEVIATION 2.47 | 9.54 years STANDARD_DEVIATION 2.23 |
| Behavior Rating Inventory of Executive Function, 2nd Edition - Global Executive Composite | 65.33 T-score STANDARD_DEVIATION 7.77 | 62.5 T-score STANDARD_DEVIATION 9.33 | 44.57 T-score STANDARD_DEVIATION 12.38 | 52.22 T-score STANDARD_DEVIATION 14.47 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 5 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 9 Participants | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 8 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 8 Participants | 10 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 4 |
| other Total, other adverse events | 0 / 5 | 0 / 4 |
| serious Total, serious adverse events | 0 / 5 | 0 / 4 |
Outcome results
Primary
Changes in Brain Segmentation Volume Produced by Stimulant or Non-stimulant Medications in Patients With ADHD
Brain segmentation volume measured in mm\^3. We are reporting the mean difference in brain segmentation volume from baseline (pre-test) to 6 weeks (post-test). No statistical analysis information is being submitted for the affected outcome measure. No statistical analyses have been performed or would be considered scientifically appropriate because actual enrollment fell well below target enrollment. Enrollment terminated early as a result of the COVID-19 pandemic.
Time frame: Baseline and 6 weeks
Population: 4 subjects from the ADHD-Guanfacine group and 3 subjects from the ADHD-Lisdexamfetamine group had usable anatomical MRI data at baseline and follow-up. HCs did not complete follow-up.~No statistical analysis information is being submitted for the affected outcome measure. No statistical analyses have been performed or would be considered scientifically appropriate because actual enrollment fell well below target enrollment. Enrollment terminated early as a result of the COVID-19 pandemic.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ADHD - Guanfacine | Changes in Brain Segmentation Volume Produced by Stimulant or Non-stimulant Medications in Patients With ADHD | -6137 mm^3 | Standard Deviation 14393 |
| ADHD - Lisdexamfetamine | Changes in Brain Segmentation Volume Produced by Stimulant or Non-stimulant Medications in Patients With ADHD | 11833 mm^3 | Standard Deviation 39942 |