ADHD
Conditions
Keywords
Attention Deficit Hyperactivity Disorder, ADHD, fMRI, Imaging, Vyvanse, Stimulant Medication, Treatment, Clinical Trial, Adult
Brief summary
The purpose of this study is to determine the effects of Vyvanse, an FDA approved medication used in the treatment of Attention Deficit Hyperactivity Disorder (ADHD), on brain activity in adults with attention-deficit hyperactivity disorder (ADHD). Participants may qualify for participation in this study because they have ADHD and are willing to participate in two Functional Magnetic Resonance Imaging (fMRI) scans and receive Vyvanse for treatment of their symptoms. Another purpose of this study is to collect and bank samples of blood for research to examine how genes influence brain activation seen during the brain scans. The study also seeks to find out whether certain genes are related to ADHD. Participants' entire genetic makeup will not be determined from this sample.
Interventions
DRUGLisdexamfetamine
Escalating stepped dose titration: 30, 50 or 70mg
Sponsors
Jeffrey Newcorn
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Primary DSM-IV-TR diagnosis of adult ADHD (inattentive, hyperactive-impulsive or combined subtype), established via the ACDS v1.2. * Must be between 18-55 years, inclusive. * Provides written informed consent.
Exclusion criteria
* Lifetime or current diagnosis of bipolar disorder, schizophrenia or schizoaffective disorder. * Current diagnosis of comorbid major depressive disorder, anxiety disorder or dysthymia or any controlled (i.e. requires pharmacological treatment) comorbid diagnosis. Participants with uncontrolled depressive or anxiety disorders may participate if, in the opinion of the Principal Investigator, the disorder will not confound the results of efficacy or safety assessments, increase risk to the participant or lead to difficulty complying with the protocol. * Meets current DSM-IV-TR criteria for alcohol or any non-alcohol substance abuse or dependence disorder. * Have organic brain disease (such as dementia) or traumatic brain injury residua. Have a history of seizure disorder (other than febrile seizures) or participants who have taken (or are currently taking) anticonvulsants for seizure control. * Females who are currently pregnant or breast feeding, and women of child-bearing potential who are not currently using an adequate form of birth control. * Participants with clinically significant abnormalities in ECG results that are deemed exclusionary in the opinion of the Principal Investigator will not be allowed in the trial. * Participants who work the night shift or another schedule that would preclude beginning the daily dose of study medication in the morning. * Participants with a positive urine drug result at Screening. * Medical conditions limiting participation in the study. * Documented history of intolerance or non-responsivity to methylphenidate or amphetamines. * Have a medical condition that would, in the opinion of the study physician, make participation medically hazardous. * ADHD, Not Otherwise Specified * History of surgery involving metal implants, metal fragments in the eyes, braces, or a pacemaker.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Go/No-Go Task Percentage Assessed by fMRI | 8 weeks | Performance Measures on the Go/No-Go Task assessed by fMRI as a Function of Trial Type, Face Emotion, and Drug Condition in Adults with Attention-Deficit/Hyperactivity Disorder. The Go/No-Go Task is a neuropsychological test that provides a direct measure of number of responses made that are correct or incorrect. It is not a scale. Reported are the percentage of correct responses on that direct performance measure. 0% correct is worse than 100% correct. |
| fMRI Reaction Time | up to 6 weeks | Reaction-time, as measured by the reaction time test Go/No-Go Task as a Function of Trial Type, Face Emotion, and Drug Condition in Adults with Attention-Deficit/Hyperactivity Disorder |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| WRAADS | Baseline | The Wender-Reimherr adult attention deficit disorder scale (WRAADS): Symptom measure for emotional functioning/lability, generally reported as Sum of Responses (0-2 per item, higher = more impaired). For this outcome measure, Average scores for particular questions were taken - specifically question 3, question 4, and question 5. |
| ADHD-RS-IV Combined Sum | Baseline | ADHD symptoms and severity. Norm referenced interview to assess severity and frequency of ADHD symptoms. 18 Items are scored 0-3 to reflect severity and frequency of ADHD symptoms, and a sum is taken. Full range from 0 to 54, with higher number indicating more symptoms and severity. |
| BRIEF-A | Baseline | Behavior Rating Inventory of Executive Function®-Adult Version (BRIEF-A): Norm Referenced Measure of Impaired Executive Functioning, reported in T-Scores (0 to 100, with 50 +/-1 SD = 'Normal', higher is worse, more impaired) |
| CGI-I | Baseline | Clinical Global Impressions - CGI-I: Clinical response was the Clinical Global Impression-Improvement scale (CGI-I). Lower CGI-I scores indicate greater improvement (1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse). |
| CGI-S | baseline | CGI-S: Severity of impairment due to ADHD was measured by the Clinical Global Impressions-Severity scale (CGI-S). Lower scores indicate less severe impairment from symptoms, with a CGI-I=1 indicating the person is normal with no impairment. (1= normal, not ill, 2= minimally ill, 3= mildly ill, 4= moderately ill, 5=markedly ill, 6=severely ill, 7= very severely ill) |
| ADHD-Inattentive | 4 weeks and 8 weeks | ADHD symptoms and severity - subscale for Inattentiveness. 9-item scale, each scored 0-3, with total from 0 to 27. Higher score indicates higher level of inattentiveness. |
| ASRS - Expanded | Baseline | ADHD and Related Symptoms Measure (ASRS): self report, reported as Sum of Responses (0-4 per item, higher = more impaired) 0-26 (normal range) and \>27 (clinically significant symptoms). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| On Drug, Then Off Drug fMRI #1 on drug, #2 off drug | 17 |
| Off Drug, Then on Drug fMRI #1 off drug, #2 on drug | 13 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout Period (2 Weeks) | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | On Drug, Then Off Drug | Off Drug, Then on Drug | Total |
|---|---|---|---|
| Age, Continuous | 35.46 years STANDARD_DEVIATION 11.82 | 37.27 years STANDARD_DEVIATION 11.81 | 35.84 years STANDARD_DEVIATION 10.25 |
| Sex: Female, Male Female | 8 Participants | 5 Participants | 13 Participants |
| Sex: Female, Male Male | 9 Participants | 8 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 11 |
| other Total, other adverse events | 14 / 14 | 11 / 11 |
| serious Total, serious adverse events | 0 / 14 | 0 / 11 |
Outcome results
Primary
fMRI Reaction Time
Reaction-time, as measured by the reaction time test Go/No-Go Task as a Function of Trial Type, Face Emotion, and Drug Condition in Adults with Attention-Deficit/Hyperactivity Disorder
Time frame: up to 6 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | fMRI Reaction Time | Happy | 532 ms | Standard Error 99 |
| Placebo | fMRI Reaction Time | Sad | 533 ms | Standard Error 110 |
| Placebo | fMRI Reaction Time | Neutral | 553 ms | Standard Error 109 |
| Lisdexamfetamine | fMRI Reaction Time | Neutral | 533 ms | Standard Error 104 |
| Lisdexamfetamine | fMRI Reaction Time | Happy | 519 ms | Standard Error 114 |
| Lisdexamfetamine | fMRI Reaction Time | Sad | 509 ms | Standard Error 96 |
Primary
The Go/No-Go Task Percentage Assessed by fMRI
Performance Measures on the Go/No-Go Task assessed by fMRI as a Function of Trial Type, Face Emotion, and Drug Condition in Adults with Attention-Deficit/Hyperactivity Disorder. The Go/No-Go Task is a neuropsychological test that provides a direct measure of number of responses made that are correct or incorrect. It is not a scale. Reported are the percentage of correct responses on that direct performance measure. 0% correct is worse than 100% correct.
Time frame: 8 weeks
Population: Performance measures are done while participants are off drug and while on drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | The Go/No-Go Task Percentage Assessed by fMRI | Happy Correct Responses | 91.7 percentage correct responses/inhibitions | Standard Error 2.8 |
| Placebo | The Go/No-Go Task Percentage Assessed by fMRI | Happy Correct Inhibitions | 88.7 percentage correct responses/inhibitions | Standard Error 9.4 |
| Placebo | The Go/No-Go Task Percentage Assessed by fMRI | Sad Correct Responses | 90.3 percentage correct responses/inhibitions | Standard Error 7.7 |
| Placebo | The Go/No-Go Task Percentage Assessed by fMRI | Sad Correct Inhibitions | 84.4 percentage correct responses/inhibitions | Standard Error 12.5 |
| Placebo | The Go/No-Go Task Percentage Assessed by fMRI | Neutral Correct Responses | 93.2 percentage correct responses/inhibitions | Standard Error 12.2 |
| Placebo | The Go/No-Go Task Percentage Assessed by fMRI | Neutral Correct Inhibitions | 77.5 percentage correct responses/inhibitions | Standard Error 12.3 |
| Lisdexamfetamine | The Go/No-Go Task Percentage Assessed by fMRI | Neutral Correct Responses | 95.6 percentage correct responses/inhibitions | Standard Error 5.8 |
| Lisdexamfetamine | The Go/No-Go Task Percentage Assessed by fMRI | Happy Correct Responses | 97.0 percentage correct responses/inhibitions | Standard Error 3.8 |
| Lisdexamfetamine | The Go/No-Go Task Percentage Assessed by fMRI | Sad Correct Inhibitions | 86.7 percentage correct responses/inhibitions | Standard Error 11.3 |
| Lisdexamfetamine | The Go/No-Go Task Percentage Assessed by fMRI | Happy Correct Inhibitions | 87.9 percentage correct responses/inhibitions | Standard Error 11.5 |
| Lisdexamfetamine | The Go/No-Go Task Percentage Assessed by fMRI | Neutral Correct Inhibitions | 79.6 percentage correct responses/inhibitions | Standard Error 11.6 |
| Lisdexamfetamine | The Go/No-Go Task Percentage Assessed by fMRI | Sad Correct Responses | 88.5 percentage correct responses/inhibitions | Standard Error 10.6 |
Secondary
ADHD-Inattentive
ADHD symptoms and severity - subscale for Inattentiveness. 9-item scale, each scored 0-3, with total from 0 to 27. Higher score indicates higher level of inattentiveness.
Time frame: 4 weeks and 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | ADHD-Inattentive | On drug | 7.36 units on a scale | Standard Deviation 4.53 |
| Placebo | ADHD-Inattentive | Placebo | 18.94 units on a scale | Standard Deviation 6.21 |
| Lisdexamfetamine | ADHD-Inattentive | On drug | 8.83 units on a scale | Standard Deviation 7.63 |
| Lisdexamfetamine | ADHD-Inattentive | Placebo | 19.2 units on a scale | Standard Deviation 5.07 |
Secondary
ADHD-RS-IV Combined Sum
ADHD symptoms and severity. Norm referenced interview to assess severity and frequency of ADHD symptoms. 18 Items are scored 0-3 to reflect severity and frequency of ADHD symptoms, and a sum is taken. Full range from 0 to 54, with higher number indicating more symptoms and severity.
Time frame: Baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | ADHD-RS-IV Combined Sum | On Drug | 11.00 units on a scale | Standard Deviation 6.98 |
| Placebo | ADHD-RS-IV Combined Sum | Placebo | 25.65 units on a scale | Standard Deviation 8.53 |
| Lisdexamfetamine | ADHD-RS-IV Combined Sum | On Drug | 13.67 units on a scale | Standard Deviation 11.64 |
| Lisdexamfetamine | ADHD-RS-IV Combined Sum | Placebo | 31.00 units on a scale | Standard Deviation 14.8 |
Secondary
ASRS - Expanded
ADHD and Related Symptoms Measure (ASRS): self report, reported as Sum of Responses (0-4 per item, higher = more impaired) 0-26 (normal range) and \>27 (clinically significant symptoms).
Time frame: at one week
Population: not collected
Secondary
ASRS - Expanded
ADHD and Related Symptoms Measure (ASRS): self report, reported as Sum of Responses (0-4 per item, higher = more impaired) 0-26 (normal range) and \>27 (clinically significant symptoms).
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | ASRS - Expanded | 83.7 units on a scale | Standard Deviation 25.59 |
| Lisdexamfetamine | ASRS - Expanded | 86 units on a scale | Standard Deviation 4.24 |
Secondary
ASRS - Expanded
ADHD and Related Symptoms Measure (ASRS): self report, reported as Sum of Responses (0-4 per item, higher = more impaired) 0-26 (normal range) and \>27 (clinically significant symptoms).
Time frame: at 4 weeks
Population: not collected
Secondary
BRIEF-A
Behavior Rating Inventory of Executive Function®-Adult Version (BRIEF-A): Norm Referenced Measure of Impaired Executive Functioning, reported in T-Scores (higher is worse)
Time frame: at one week
Population: not collected
Secondary
BRIEF-A
Behavior Rating Inventory of Executive Function®-Adult Version (BRIEF-A): Norm Referenced Measure of Impaired Executive Functioning, reported in T-Scores (0 to 100, with 50 +/-1 SD = 'Normal', higher is worse, more impaired)
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | BRIEF-A | 66.64 t-score | Standard Deviation 11.89 |
| Lisdexamfetamine | BRIEF-A | 73.5 t-score | Standard Deviation 14.75 |
Secondary
BRIEF-A
Behavior Rating Inventory of Executive Function®-Adult Version (BRIEF-A): Norm Referenced Measure of Impaired Executive Functioning, reported in T-Scores (higher is worse)
Time frame: at 4 weeks
Population: not collected
Secondary
CGI-I
Clinical Global Impressions - CGI-I: Clinical response was the Clinical Global Impression-Improvement scale (CGI-I). Lower CGI-I scores indicate greater improvement (1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse).
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | CGI-I | 1.88 units on a scale | Standard Deviation 1.13 |
| Lisdexamfetamine | CGI-I | 2.00 units on a scale | Standard Deviation 1.41 |
Secondary
CGI-S
CGI-S: Severity of impairment due to ADHD was measured by the Clinical Global Impressions-Severity scale (CGI-S). Lower scores indicate less severe impairment from symptoms, with a CGI-I=1 indicating the person is normal with no impairment. (1= normal, not ill, 2= minimally ill, 3= mildly ill, 4= moderately ill, 5=markedly ill, 6=severely ill, 7= very severely ill)
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | CGI-S | 4.9 units on a scale | Standard Deviation 1 |
| Lisdexamfetamine | CGI-S | 4.95 units on a scale | Standard Deviation 0.9 |
Secondary
WRAADS
The Wender-Reimherr adult attention deficit disorder scale (WRAADS): Symptom measure for emotional functioning/lability, generally reported as Sum of Responses (0-2 per item, higher = more impaired). For this outcome measure, Average scores for particular questions were taken - specifically question 3, question 4, and question 5.
Time frame: Baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | WRAADS | Question 3 | 0.80 units on a scale | Standard Deviation 0.86 |
| Placebo | WRAADS | Question 4 | 1.27 units on a scale | Standard Deviation 1.22 |
| Placebo | WRAADS | Question 5 | 1.13 units on a scale | Standard Deviation 1.35 |
| Lisdexamfetamine | WRAADS | Question 3 | 0.94 units on a scale | Standard Deviation 0.745 |
| Lisdexamfetamine | WRAADS | Question 4 | 1.47 units on a scale | Standard Deviation 1.23 |
| Lisdexamfetamine | WRAADS | Question 5 | 1.82 units on a scale | Standard Deviation 1.19 |