Back to resultsNeurobiological Basis of Response to Vyvanse in Adults With ADHD: an fMRI Study of Brain Activation
Primary Purpose
ADHD
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Lisdexamfetamine
Sponsored by
About this trial
This is an interventional basic science trial for ADHD focused on measuring Attention Deficit Hyperactivity Disorder, ADHD, fMRI, Imaging, Vyvanse, Stimulant Medication, Treatment, Clinical Trial, Adult
Eligibility Criteria
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.
Sites / Locations
- Icahn School of Medicine at Mount Sinai
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
On Drug then off Drug
Off drug then on drug
Arm Description
Participants receive fMRI #1 on drug, #2 off drug Escalating stepped titration: 30, 50 or 70mg
Participants receive fMRI #1 off drug, #2 on drug Escalating stepped dose titration: 30, 50, 70mg
Outcomes
Primary Outcome Measures
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.
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
Secondary Outcome Measures
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)
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)
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)
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).
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).
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).
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.
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.
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.
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).
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)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01924429
Brief Title
Neurobiological Basis of Response to Vyvanse in Adults With ADHD: an fMRI Study of Brain Activation
Official Title
Neurobiological Basis of Response to Vyvanse in Adults With ADHD: an fMRI Study of Brain Activation
Study Type
Interventional
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
March 2013 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jeffrey Newcorn
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ADHD
Keywords
Attention Deficit Hyperactivity Disorder, ADHD, fMRI, Imaging, Vyvanse, Stimulant Medication, Treatment, Clinical Trial, Adult
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
On Drug then off Drug
Arm Type
Experimental
Arm Description
Participants receive fMRI #1 on drug, #2 off drug Escalating stepped titration: 30, 50 or 70mg
Arm Title
Off drug then on drug
Arm Type
Experimental
Arm Description
Participants receive fMRI #1 off drug, #2 on drug Escalating stepped dose titration: 30, 50, 70mg
Intervention Type
Drug
Intervention Name(s)
Lisdexamfetamine
Other Intervention Name(s)
Vyvanse
Intervention Description
Escalating stepped dose titration: 30, 50 or 70mg
Primary Outcome Measure Information:
Title
The Go/No-Go Task Percentage Assessed by fMRI
Description
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
Title
fMRI Reaction Time
Description
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
Secondary Outcome Measure Information:
Title
BRIEF-A
Description
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
Title
BRIEF-A
Description
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
Title
BRIEF-A
Description
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
Title
ASRS - Expanded
Description
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
Title
ASRS - Expanded
Description
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
Title
ASRS - Expanded
Description
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
Title
WRAADS
Description
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
Title
ADHD-RS-IV Combined Sum
Description
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
Title
ADHD-Inattentive
Description
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
Title
CGI-I
Description
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
Title
CGI-S
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey Newcorn, MD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
29661516
Citation
Schulz KP, Krone B, Adler LA, Bedard AV, Duhoux S, Pedraza J, Mahagabin S, Newcorn JH. Lisdexamfetamine Targets Amygdala Mechanisms That Bias Cognitive Control in Attention-Deficit/Hyperactivity Disorder. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018 Aug;3(8):686-693. doi: 10.1016/j.bpsc.2018.03.004. Epub 2018 Mar 19.
Results Reference
derived
Learn more about this trial
Neurobiological Basis of Response to Vyvanse in Adults With ADHD: an fMRI Study of Brain Activation
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