Control of Cognition (Naltrexone, Methylphenidate, and ADHD Study (NMAS)) (NMAS)

Control of Cognition: Naltrexone, Methylphenidate, and ADHD Study

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.

Study Overview

• Status: Completed
• Conditions: Healthy; Attention Deficit Hyperactivity Disorder
• Intervention / Treatment: Drug: Methylphenidate; Drug: Naltrexone; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-2700
      • Rachel Upjohn Building, East Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Methylphenidate; One dose 40mgs of methylphenidate one hour before fMRI scanning.; Other Names: Ritalin; Drug: Naltrexone; One dose 40mgs of naltrexone one hour before fMRI scanning.; Other Names: ReVia; Drug: Placebo; One dose of placebo one hour before fMRI scanning.; Other Names: sugar pill
Experimental: 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.	Drug: Methylphenidate; One dose 40mgs of methylphenidate one hour before fMRI scanning.; Other Names: Ritalin; Drug: Naltrexone; One dose 40mgs of naltrexone one hour before fMRI scanning.; Other Names: ReVia; Drug: Placebo; One dose of placebo one hour before fMRI scanning.; Other Names: sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reaction Time on the Multi-Source Interference Task	Reaction time of the Multi-Source Interference Task is measured in seconds.	Two hours
Accuracy on the Multi-Source Interference Task	Accuracy is the calculated percentage of correct responses over total trials in the Multi-Source Interference Task.	Two hours
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.	Two hours

Collaborators and Investigators

• Sponsor: University of Michigan
• Investigators: Principal Investigator: Chandra Sekhar Sripada, MD, PhD, University of Michigan

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: November 13, 2013
• First Submitted That Met QC Criteria: November 20, 2013
• First Posted (Estimate): November 25, 2013

Study Record Updates

• Last Update Posted (Actual): June 18, 2018
• Last Update Submitted That Met QC Criteria: May 17, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Naltrexone; Neuroimaging; Motor Control; Placebo; Methylphenidate; Prefrontal Control Circuits; Attention Control; Appetitive Control
• Additional Relevant MeSH Terms: Mental Disorders; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Sensory System Agents; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Narcotic Antagonists; Alcohol Deterrents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Naltrexone; Methylphenidate
• Other Study ID Numbers: HUM00047129

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No