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

Attention Deficit Hyperactivity Disorder Clinical Trial

— MPH-ATX  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03781765
• Other study ID #: GCO 17-0423
• Secondary ID: 1R21DA045218-01A
• Status: Recruiting
• Phase: Phase 4
• Start date: June 4, 2019
• Est. completion date: November 2024

Study information

• Verified date: April 2023
• Source: Icahn School of Medicine at Mount Sinai
• Contact: Beth Krone, PhD
• Phone: 212-241-8012
• Email: beth.krone[@]mssm.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: November 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years to 12 Years

Eligibility

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

Related Conditions & MeSH terms

• ADHD
• Attention Deficit Disorder with Hyperactivity
• Attention Deficit Hyperactivity Disorder

Intervention

Drug:
• Methylphenidate
stimulant medication
• Atomoxetine
non-stimulant medication

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	fMRI Measure	Bold activation change within the reward system (e.g., ventral striatum, insula and orbitofrontal cortex)	3 Weeks