Stimulant vs. Non-stimulant Treatments and Reward Processing in Drug-naive Youth at SUD Risk

NCT ID: NCT03781765

Last Updated: 2024-08-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-04
• Study Completion Date: 2025-09-25

Brief Summary

The study team will examine the effects of FDA approved stimulant and non-stimulant medications for ADHD, among youth with ADHD and with and without Oppositional Defiant Disorder (ODD) or Conduct Disorder (CD), on reward systems of the brain using fMRI.

Detailed Description

Longitudinal studies have shown that childhood Attention Deficit/Hyperactivity Disorder (ADHD) and child disruptive behavior disorders play an important role in the development of later Substance Use Disorders (SUD). Although available evidence suggests that abnormal reward processing is likely to mediate vulnerability for addiction, the functioning of the brain reward systems in at-risk individuals preceding the exposure to drugs remains largely unknown. Better understanding the baseline characteristics of reward processing in drug-naïve individuals at risk for later SUD is an important initial step in refining our knowledge of the neurobiological basis of addiction. Reward processing in at-risk individuals may be further influenced by exposure to first-line treatments (e.g. methylphenidate (MPH)) for ADHD that also happen to be controlled substances.

Findings from animal research have raised the possibility that stimulants such as methylphenidate (MPH) may have "sensitization" effects - which prime the brain reward system for enhanced responding to the rewarding effects of abusable substances, whereas non-stimulants such as atomoxetine (ATX) may diminish drug self-administration. However, no studies have examined the purported different effects of stimulants vs. non-stimulants on the brain reward system utilizing a targeted biomarker approach linked to an a priori model, which focuses on intermediate phenotypes. Such research could provide important knowledge regarding the biological basis of addiction vulnerability and aid in the development of preventive interventions.

This proposal will provide pilot data for the hypotheses that stimulant and non-stimulant medications have differential effects on activation in the brain reward system in High Risk (HR) youth, and that differences activation will be related to changes in measures of reward sensitivity on psychometric tests. The study team believes that this protocol is uniquely innovative in its approach to study drug-naïve children at the highest levels of risk for SUD, thus providing an opportunity to delineate differential effects of medication treatment in relation to SUD risk. This research is also significant since it will be the first neuroimaging study to assess the biological correlates of the effects of stimulants on reward sensitivity in HR children, and especially in relation to purported changes in reward processing.

Conditions

ADHD; Attention Deficit Hyperactivity Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Methylphenidate

0.5 mg/kg for 1 week and 1 mg/kg for 2 weeks

Group Type: ACTIVE_COMPARATOR

Methylphenidate

Intervention Type: DRUG

stimulant medication

Atomoxetine

0.5 mg/kg for 1 week and 1 mg/kg for 2 weeks

Group Type: ACTIVE_COMPARATOR

Atomoxetine

Intervention Type: DRUG

non-stimulant medication

Interventions

Methylphenidate

stimulant medication

Intervention Type: DRUG

Atomoxetine

non-stimulant medication

Intervention Type: DRUG

Other Intervention Names

MPH; ATX

Eligibility Criteria

Inclusion Criteria

• Pre-pubertal (e.g. Tanner stage 1 or 2)
• Age 7-12 inclusive
• Signed consent/assent
• Parent communicates sufficiently in English to provide informed consent and complete assessment instruments;
• ADHD as determined by computerized DISC (C-DISC) parent interview
• ADHD-Rating Scale-5 total score (interview with parent )
• SNAP ADHD total score (teacher) of 1.5 SD > age/sex norms
• CD or severe ODD: CD or ODD + 2 symptoms of CD on C-DISC
• SNAP ODD/CD subscale (parent and teacher) 1.5 SD > age/sex norms

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)75 score <75
• Prior or current treatment with stimulants (prior or current treatment with non-stimulants is permitted, but participants must be off medication for 2 weeks at baseline)
• Current or past alcohol/drug use (DISC 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 (e.g., braces, metal plate)
• Visual disturbances that may impair task performance
• Precocious puberty (e.g. Tanner stage >2) or pregnancy

Notes:

• History of SUD in a 1st degree relative is permitted, and is expected in ~1/2 of the subjects
• Ongoing psychosocial treatment is allowed but should not be initiated during the study

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: lead

Responsible Party

Jeffrey Newcorn

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeffrey Newcorn, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Iliyan Ivanov, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Beth Krone, PhD

Role: CONTACT

beth.krone@mssm.edu

212-241-8012

Jeffrey Newcorn, MD

Role: CONTACT

Facility Contacts

Beth Krone, PhD

Role: primary

beth.krone@mssm.edu

212-241-8012

Other Identifiers

1R21DA045218-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

GCO 17-0423

Identifier Type: -

Identifier Source: org_study_id