Clinical trial NCT03781765: Stimulant vs. Non-stimulant Treatments and Reward Processing in Drug-naive Youth at SUD Risk
Official title: Stimulant vs. Non-stimulant Treatments and Reward Processing in Drug-naive Youth at SUD Risk
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: ADHD
Attention Deficit Hyperactivity Disorder
Keywords: fMRI Study
MPH
Methylphenidate
ATX
Atomoxetine
Reward System
Substance Abuse Risk
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2018-12-20
Enrollment: 44
Sex: ALL
Minimum age (years): 7
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: This is a pilot study with no control group. All youth will be treated with MPH or ATX and receive pre and post fMRI.
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: fMRI Measure
timeFrame: 3 Weeks
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Jeffrey Newcorn, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Iliyan Ivanov, MD
role: PRINCIPAL_INVESTIGATOR
References: