Brain Indices of Stimulant Treatment in Drug-Naive Youth at Risk for Substance Use Disorder

Childhood ADHD and comorbid oppositional defiant disorder (ODD) and conduct disorder (CD) are considered risk factors for subsequent substance abuse, and youth with both ADHD and ODD/CD are at greatest risk.

However, the effects of treatment of ADHD with stimulant medications such as methylphenidate (MPH) and mixed amphetamine salts (MAS) on risk for substance abuse are poorly understood. The study team propose to use fMRI to study the effects of extended release mixed amphetamine salts (MAS-XR) in drug-naïve youth 7-12 years at low risk (i.e., ADHD only) and high risk (i.e., ADHD + ODD/CD) for substance abuse on the brain reward system, to better understand the potential impact of these medications on an aspect of brain functioning which is thought to underlie vulnerability to substance abuse.

Study Overview

• Status: Completed
• Conditions: Conduct Disorder; Substance Abuse; Attention Deficit Disorder With Hyperactivity
• Intervention / Treatment: Drug: Adderall

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School Of Medicine At Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 12 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• General: pre-pubertal (e.g. Tanner stage 1 or 2)
• age 7-12 inclusive
• signed consent/assent
• parent communicates sufficiently in English
• Has ADHD as determined by parent interview
• ADHD-Rating Scale-5 total score (interview with parent) of 1.5 SD > age/sex norms
• Youth with CD or severe ODD: CD or ODD + 2 symptoms of CD

Exclusion Criteria:

• major neurological/medical illness
• history of head injury
• fetal exposure to alcohol/drugs;
• diagnosis of major psychiatric disorder (e.g., schizophrenia, bipolar disorder, major depression, generalized anxiety, social phobia, Tourette's Disorder, PTSD, autism spectrum disorder) current suicidal ideation or past history of suicide attempt
• Wechsler Abbreviated Scale of Intelligence (WASI) score <75; 7)
• current treatment with stimulants (prior or current treatment with non-stimulants is permitted, but participants must be off medication for 2 weeks at baseline; youth who had a past, brief stimulant medication exposure of no more than about a month, and not within the past 6 months may be included .)
• current or past alcohol/drug use (interview; urine toxicology)
• psychological or medical condition which precludes being in the scanner (e.g., claustrophobia, morbid obesity)
• metal in the body that cannot be removed
• visual disturbances that may impair task performance
• precocious puberty (e.g. Tanner stage >2).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adderall; dosage = start at 0.25-0.50mg/kg, adjusted as necessary pills by mouth	Drug: Adderall; 3 weeks of Adderall; Other Names: Dextroamphetamine-Amphetamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in fMRI Measure	Bold activation change within the reward system. The contrasts in blood-oxygenation levels (BOLD) in regions of interest (ROIs).	baseline and 3 weeks post intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ADHD Rating Score (ADHD RS)	Subscale for Inattention scores range from 0-27, Subscale scores for Hyper (H/I) range from 0-27. The total ADHD score sums to a score of 0-54. Higher indicates more severe ADHD symptomology, and there are norm ranges, with clinical thresholds set at 1.5 SD above the mean for sex and age.	Pretreatment, baseline and Post-Treatment, average 2 weeks
Total Dose of MAS-XR	Open label trial of MAS XR with flexible dosing and a suggested target of at least 0.5mg/kg	average 2 weeks
Change in Clinical Global Impression - Improvement (CGI-I)	The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. Change in CGi post treatment as compared to baseline.	baseline and post treatment, average 2 weeks

Collaborators and Investigators

• Sponsor: Jeffrey Newcorn
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Iliyan Ivanov, MD, Icahn School Of Medicine At Mount Sinai; Principal Investigator: Jeffrey Newcorn, MD, Icahn School Of Medicine At Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2019
• Primary Completion (Actual): August 8, 2023
• Study Completion (Actual): August 8, 2023

Study Registration Dates

• First Submitted: November 18, 2019
• First Submitted That Met QC Criteria: November 18, 2019
• First Posted (Actual): November 20, 2019

Study Record Updates

• Last Update Posted (Actual): August 29, 2024
• Last Update Submitted That Met QC Criteria: August 7, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: ADHD; fMRI; Medication; Adderall; substance abuse risk; ADHD Treatment
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Substance-Related Disorders; Attention Deficit Disorder with Hyperactivity; Conduct Disorder; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Sympathomimetics; Adrenergic Uptake Inhibitors; Amphetamine; Dextroamphetamine; Adderall
• Other Study ID Numbers: GCO 17-1321; 1R21DA046029-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).

Drug and device information, study documents

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