Attention Deficit Hyperactivity Disorder, Healthy
Conditions
Keywords
Methylphenidate, Naltrexone, Placebo, Neuroimaging, Prefrontal Control Circuits, Attention Control, Motor Control, Appetitive Control
Brief summary
The goal of this research is to understand the functioning of 'regulatory circuits' in the brain. We are also interested in how the medications methylphenidate and naltrexone affect these regulatory circuits. This research study will use a scanning technique known as functional magnetic resonance imaging (fMRI) which takes a special kind of picture of the brain that enables us to see the brain at work. Adult participants will be given a one-time dose of either methylphenidate, naltrexone,or placebo before each fMRI scan session. The main purpose for this research is to better understand the functioning of regulatory circuits in healthy individuals and individuals with psychiatric disorders. This research may one day help us develop better treatments for these disorders.
Detailed description
The goal of this research is to understand the functioning of 'regulatory circuits' in the brain. These are brain circuits which allow a person to regulate their attention, regulate their behavioral responses, and regulate their decision-making. We are also interested in how the medications methylphenidate and naltrexone affect these regulatory circuits. Methylphenidate is a widely-used, FDA approved medication used to treat Attention Deficit Hyperactivity Disorder (ADHD) and is also known as Ritalin. Naltrexone is an FDA approved medication used to help treat alcohol and substance abuse. This research study will use a scanning technique known as functional magnetic resonance imaging (fMRI)which takes a special kind of picture of the brain that enables us to see the brain at work. Adult participants will be given a one-time dose of either methylphenidate, naltrexone,or placebo before each fMRI scan session. There are three total fMRI scan sessions. Therefore, each participant will receive each possible medication/placebo only once. Using the fMRI technique, the main purpose of this research is to better understand the functioning of regulatory circuits in healthy individuals and individuals with psychiatric disorders. This research may one day help us develop better treatments for these disorders.
Interventions
DRUGMethylphenidate
One dose 40mgs of methylphenidate one hour before fMRI scanning.
DRUGNaltrexone
One dose 40mgs of naltrexone one hour before fMRI scanning.
DRUGPlacebo
One dose of placebo one hour before fMRI scanning.
Sponsors
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
for all study participants: * Right-Handedness
Exclusion criteria
for all study participants: * Any clinically significant history of cardiac problems * Any current Axis I psychiatric diagnosis as verified by the Structured Clinical Interview for DSM-IV (other than participants with ADHD or history of alcohol dependence) * A previous adequate trial with methylphenidate (Ritalin) or naltrexone (ReVia) * Currently taking any psychoactive medications * Any clinically significant medical condition * Any clinically significant neurological problem (seizures, tics, serious head injury) * Contraindications to MRI (metal objects in body or claustrophobia) * Currently pregnant or lactating * Alcohol or substance abuse (current or in the past 2 years) * Left-handedness or ambidextrous * Liver or kidney disease Inclusion Criteria for the participants with ADHD: * Currently un-medicated adults with ADHD * Has met full DSM-IV-R criteria (at least six of nine symptoms)for inattentive or hyperactive/impulsive subtypes (or both) by age 7 as well within the past month * Has described a chronic course of ADHD symptomatology from childhood to adulthood * Has endorsed a moderate or severe level of impairment attributed to the ADHD symptoms
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reaction Time Variability on the Multi-Source Interference Task | 2 hours | Multi-Source Interference Task is a psychological task that measures the psychological construct of cognitive control, the ability to suppress automatic response tendencies. Reaction time variability is the standard deviation of the trial to trial reaction time measured in seconds. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reaction Time on the Multi-Source Interference Task | Two hours | Reaction time of the Multi-Source Interference Task is measured in seconds. |
| Accuracy on the Multi-Source Interference Task | Two hours | Accuracy is the calculated percentage of correct responses over total trials in the Multi-Source Interference Task. |
| Characterize the Effects of Methylphenidate and Naltrexone on Neural Circuits in Prefrontal Cortex Associated With Top-down Control. | Two hours | The effects of methylphenidate, naltrexone, and placebo on the change in BOLD (Blood Oxygen Level Dependent) signal will be characterized in the incongruent condition (cognitive regulation condition) of the MSIT (multi-source interference task) relative to the congruent condition (no regulation condition). Specifically, the summed BOLD signal in three regions--dorsal lateral prefrontal cortex, anterior insula, anterior cingulate--are measured. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Controls Healthy individuals will receive a one-time, randomized dose of 40mgs of Methylphenidate, 40mgs of Naltrexone, and a placebo one hour before the fMRI scanning session.
Methylphenidate: One dose 40mgs of methylphenidate one hour before fMRI scanning.
Naltrexone: One dose 40mgs of naltrexone one hour before fMRI scanning.
Placebo: One dose of placebo one hour before fMRI scanning. | 11 |
| Adult Attention-Deficit/Hyperactivity Disorder ADHD individuals will receive a one-time, randomized dose of 40mgs of Methylphenidate, 40mgs of Naltrexone, and a placebo one hour before the fMRI scanning session.
Methylphenidate: One dose 40mgs of methylphenidate one hour before fMRI scanning.
Naltrexone: One dose 40mgs of naltrexone one hour before fMRI scanning.
Placebo: One dose of placebo one hour before fMRI scanning. | 12 |
| Total | 23 |
Baseline characteristics
| Characteristic | Adult Attention-Deficit/Hyperactivity Disorder | Total | Healthy Controls |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 23 Participants | 11 Participants |
| Age, Continuous | 22.08 years STANDARD_DEVIATION 3.4 | 23.4 years STANDARD_DEVIATION 4.4 | 24.9 years STANDARD_DEVIATION 5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 15 Participants | 7 Participants |
| Region of Enrollment United States | 12 Participants | 23 Participants | 11 Participants |
| Sex: Female, Male Female | 7 Participants | 15 Participants | 8 Participants |
| Sex: Female, Male Male | 5 Participants | 8 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 23 | 0 / 23 |
| other Total, other adverse events | 0 / 23 | 0 / 23 | 0 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 | 0 / 23 |
Outcome results
Primary
Reaction Time Variability on the Multi-Source Interference Task
Multi-Source Interference Task is a psychological task that measures the psychological construct of cognitive control, the ability to suppress automatic response tendencies. Reaction time variability is the standard deviation of the trial to trial reaction time measured in seconds.
Time frame: 2 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methlyphenidate in Healthy Controls | Reaction Time Variability on the Multi-Source Interference Task | .22 seconds | Standard Deviation 0.07 |
| Naltrexone in Healthy Controls | Reaction Time Variability on the Multi-Source Interference Task | .23 seconds | Standard Deviation 0.06 |
| Placebo in Healthy Controls | Reaction Time Variability on the Multi-Source Interference Task | .26 seconds | Standard Deviation 0.06 |
| Methlyphenidate in ADHD | Reaction Time Variability on the Multi-Source Interference Task | .20 seconds | Standard Deviation 0.06 |
| Naltrexone in ADHD | Reaction Time Variability on the Multi-Source Interference Task | .20 seconds | Standard Deviation 0.05 |
| Placebo in ADHD | Reaction Time Variability on the Multi-Source Interference Task | .21 seconds | Standard Deviation 0.06 |
p-value: 0.02t-test, 2 sided
p-value: 0.118t-test, 2 sided
p-value: 0.349t-test, 2 sided
p-value: 0.348t-test, 2 sided
Secondary
Accuracy on the Multi-Source Interference Task
Accuracy is the calculated percentage of correct responses over total trials in the Multi-Source Interference Task.
Time frame: Two hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methlyphenidate in Healthy Controls | Accuracy on the Multi-Source Interference Task | 96 percent of total trials | Standard Deviation 2 |
| Naltrexone in Healthy Controls | Accuracy on the Multi-Source Interference Task | 93 percent of total trials | Standard Deviation 7 |
| Placebo in Healthy Controls | Accuracy on the Multi-Source Interference Task | 91 percent of total trials | Standard Deviation 8 |
| Methlyphenidate in ADHD | Accuracy on the Multi-Source Interference Task | 93 percent of total trials | Standard Deviation 10 |
| Naltrexone in ADHD | Accuracy on the Multi-Source Interference Task | 93 percent of total trials | Standard Deviation 8 |
| Placebo in ADHD | Accuracy on the Multi-Source Interference Task | 92 percent of total trials | Standard Deviation 5 |
p-value: 0.049t-test, 2 sided
p-value: 0.497t-test, 2 sided
p-value: 0.814t-test, 2 sided
p-value: 0.593t-test, 2 sided
Secondary
Characterize the Effects of Methylphenidate and Naltrexone on Neural Circuits in Prefrontal Cortex Associated With Top-down Control.
The effects of methylphenidate, naltrexone, and placebo on the change in BOLD (Blood Oxygen Level Dependent) signal will be characterized in the incongruent condition (cognitive regulation condition) of the MSIT (multi-source interference task) relative to the congruent condition (no regulation condition). Specifically, the summed BOLD signal in three regions--dorsal lateral prefrontal cortex, anterior insula, anterior cingulate--are measured.
Time frame: Two hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methlyphenidate in Healthy Controls | Characterize the Effects of Methylphenidate and Naltrexone on Neural Circuits in Prefrontal Cortex Associated With Top-down Control. | .21 Mean percentage of BOLD signal change | Standard Deviation 0.51 |
| Naltrexone in Healthy Controls | Characterize the Effects of Methylphenidate and Naltrexone on Neural Circuits in Prefrontal Cortex Associated With Top-down Control. | .51 Mean percentage of BOLD signal change | Standard Deviation 0.58 |
| Placebo in Healthy Controls | Characterize the Effects of Methylphenidate and Naltrexone on Neural Circuits in Prefrontal Cortex Associated With Top-down Control. | .20 Mean percentage of BOLD signal change | Standard Deviation 0.45 |
| Methlyphenidate in ADHD | Characterize the Effects of Methylphenidate and Naltrexone on Neural Circuits in Prefrontal Cortex Associated With Top-down Control. | .43 Mean percentage of BOLD signal change | Standard Deviation 0.4 |
| Naltrexone in ADHD | Characterize the Effects of Methylphenidate and Naltrexone on Neural Circuits in Prefrontal Cortex Associated With Top-down Control. | .58 Mean percentage of BOLD signal change | Standard Deviation 0.59 |
| Placebo in ADHD | Characterize the Effects of Methylphenidate and Naltrexone on Neural Circuits in Prefrontal Cortex Associated With Top-down Control. | .47 Mean percentage of BOLD signal change | Standard Deviation 0.56 |
p-value: 0.926t-test, 2 sided
p-value: 0.126t-test, 2 sided
p-value: 0.852t-test, 2 sided
p-value: 0.552t-test, 2 sided
Secondary
Reaction Time on the Multi-Source Interference Task
Reaction time of the Multi-Source Interference Task is measured in seconds.
Time frame: Two hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methlyphenidate in Healthy Controls | Reaction Time on the Multi-Source Interference Task | .78 seconds | Standard Deviation 0.12 |
| Naltrexone in Healthy Controls | Reaction Time on the Multi-Source Interference Task | .83 seconds | Standard Deviation 0.1 |
| Placebo in Healthy Controls | Reaction Time on the Multi-Source Interference Task | .85 seconds | Standard Deviation 0.14 |
| Methlyphenidate in ADHD | Reaction Time on the Multi-Source Interference Task | .71 seconds | Standard Deviation 0.1 |
| Naltrexone in ADHD | Reaction Time on the Multi-Source Interference Task | .73 seconds | Standard Deviation 0.09 |
| Placebo in ADHD | Reaction Time on the Multi-Source Interference Task | .77 seconds | Standard Deviation 0.1 |
p-value: 0.019t-test, 2 sided
p-value: 0.24t-test, 2 sided
p-value: 0.081t-test, 2 sided
p-value: 0.247t-test, 2 sided