Adverse Adolescent Pathways to Substance Use

NCT06977178 | Recruiting

• 2 other identifiers: 23-15725R01DA057312-02
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

Purpose: This 5-year R01 study will elucidate the role of maturational change across adolescence in neural connectivity and physiological stress responses in the relationship between anxiety and adverse pathways to substance use (APSU). Participants: Children (N=200) aged 12-14 with symptoms of anxiety and their legal caregiver will be recruited from clinical and community sources. Procedures: Youth participants will complete several questionnaires and interviews, undergo neuroimaging while performing cognitive tasks, and have their heart rate and skin conductance monitored during a mildly stressful task. Caregivers will complete several questionnaires.

Conditions

Anxiety; Adolescent Development; Substance Use

Outcome Measures

Primary Outcomes (12)

• Reaction time during the functional magnetic resonance imaging (FMRI) Stop Signal Task

  The Stop Signal Task is a measure of inhibitory control. Participants are presented with a right or left arrow and instructed to press one of two buttons corresponding with each arrow after it is presented. However, on certain trials, there is an up facing arrow immediately following the presentation of a left or right arrow, and participants are instructed to not press any buttons if they see an up arrow. The task measures the mean go reaction time to evaluate the participant's ability to inhibit when the up arrow is presented, with faster reaction times (measured in milliseconds) meaning lower inhibition.

  baseline, 12-months, 24-months

• Percent signal change during the FMRI Stop Signal Task

  Neural activation during the Stop Signal Task is measured through determining the percent signal change from baseline FMRI resting state to neural activation during the Stop Signal Task, particularly in the front-striatal-thalamic regions. Higher percent signal change would indicate higher levels of activation during the task. Percent signal change ranges between 1% to 5%.

  baseline, 12-months, 24-months

• Percent signal change activation during the No-stimuli, Predictable-stimuli, and Unpredictable-stimuli (NPU) task

  In the NPU task, participants are presented with fearful and neutral faces, with the fearful face presentation being sometimes cued with another associated visual stimuli immediately beforehand, and sometimes uncued and therefore unpredicted. This task measures cued anticipation of threat. The regions of interest are the intra-limbic regions, bed nucleus of the stria terminalis (BNST), and the amygdala. Higher percent signal change in these regions would indicate higher levels of activation during the task. Percent signal change ranges between 1% to 5%.

  baseline, 12-months, 24-months

• Percent signal change during the Attentional Load Paradigm (ALP) task

  In the ALP task, participants complete a letter search task while being presented with peripheral distractor letters on top of both fearful and neutral faces to evaluate the impact of perceptual load on the neural response to fearful vs neutral face distractors. The percent signal change will be specifically analyzed in the parietal and frontal cortices. Higher percent signal change in these regions would indicate higher levels of activation during the task. In addition, the ability to shift from affective-limbic to cognitive-pre-frontal cortex to complete the task will be evaluated as a key indicator of neural maturity. Percent signal change ranges between 1% to 5%.

  baseline, 12-months, 24-months

• Percent signal change during Emotional Face N-Back (EFNBack)

  In the EFNBack task, participants are shown images of emotionally salient (happy and fearful) and neutral faces as well as images of neutral places. Participants are instructed to determine whether each picture presented is a "Match" or a "No match". In the 0-back, low load condition, the "match" occurs when the picture presented is the same as a fixed target picture presented at the beginning. In the 2-back, high load condition, the "match" occurs when the picture presented is the same as the one shown two pictures ago. This task evaluates working memory and emotional regulation, as well as the percent signal change of the prefrontal cortex (PFC), amygdala, and anterior cingulate cortex (ACC), with higher percent signal change in these regions indicating higher levels of activation during the task. Percent signal change ranges between 1% to 5%.

  baseline, 12-months, 24-months

• Sympathetic and Parasympathetic nervous system ECG activation or heart rate variability (HRV) during a psychosocial stressful task (Trier Social Stress Test - TSST)

  The Trier Social Stress Test for Children (TSST-C) -- a social stressor involving story telling in front of two neutral judges, preparation time and a cognitive stressor involving mental arithmetic-counting backward from 1023 by 13s -- is used to elicit physiological stress responses. The combination of stressors offers high levels of social-evaluative threat. The TSST-C will be administered in 4 parts: an anticipatory stress phase (5 min to prepare the speech); the speech task (5 min), the arithmetic task (5 min), and the recovery phase (up through 40 min post-task). For a five minute baseline period, and for the duration of the task, heart rate is measured to determine baseline resting state and HRV. HRV is the difference in the milliseconds between each heart beat. The higher the HRV, the more the nervous system is activated during the task. The level of HRV indicates the participant's nervous system response to stress.

  at baseline, 12-month and 24-month

• Endocrine (cortisol) measures during a psychosocial stressful task (Trier Social Stress Test - TSST)

  The Trier Social Stress Test for Children (TSST-C) -- a social stressor involving story telling in front of two neutral judges, preparation time and a cognitive stressor involving mental arithmetic-counting backward from 1023 by 13s-- is used to elicit physiological stress responses. The combination of these stressors offers elements of uncontrollability and high levels of social-evaluative threat. The TSST-C will be administered in 4 parts: an anticipatory stress phase (5 min to prepare the speech); the speech task (5 min), the arithmetic task (5 min), and the recovery phase (up through 40 min post-task). At rest, cortisol is collected through a saliva sample of passive drool. Then cortisol will be collected in 15 minute intervals for the duration of the task and recovery time. The higher the cortisol is found to be, the higher the stress response to the task.

  at baseline, 12-month and 24-month

• Assessment of Liability and Exposure to Substance Use and Antisocial Behavior, Revised (ALEXSA-R)

  The Assessment of Liability and Exposure to Substance use and Antisocial behavior, Revised (ALEXSA-R) is a system of youth-report measures of risks, resiliencies, risky health behavior. The youth-report Youth Risk Index (YRI) which is part of the ALEXSA-R will be used to screen for participants who are at high and low risk for early- to mid-adolescent problematic substance use. The YRI screening tool is designed for well-child visits to identify at-risk youths and refer them for prevention. The higher the YRI score (range 0-3) the higher the youth risk level.

  at baseline, 12-month and 24-month

• Neurocognitive testing and executive functioning through NIH Toolbox

  Neurodevelopmental maturity and cognitive functioning will be evaluated with NIH Cognitive Toolbox - Child Computerized performance tasks. These tasks test decision making, impulsivity, working memory, and attention. There is a memory task involving remembering the sequence of words, there is an inhibitory task involving pressing only certain buttons, and an attention task involving determining which pictures match and which do not. Each task produces a t score, with higher scores indicating higher performance on each task.

  at baseline, 12-month and 24-month

• Multidimensional Anxiety Scale for Children 2 (MASC2)

  The MASC2 is a comprehensive assessment of anxiety. It is a self-report scale for youth ages 8-19 with 50 items. It measures symptom severity, as well as range of symptoms across possible anxiety disorders and produces a t score which represents anxiety severity. This score can range from less than 40 (a low score) to above 70 (a high score).

  at baseline, 12-month and 24-month

• State-Trait Anxiety Inventory for Children (STAI-C)

  The STAI-C is a measure with two sub-surveys, with each one having 20 items each. The State measure assesses current anxiety at the moment of assessment, with a higher score meaning higher current anxiety. The Trait measure assesses level of anxiety severity in general as a trait of the participant, with a higher score meaning higher overall anxiety. The range in scores is between 20-80 for each sub-survey.

  at baseline, 12-month and 24-month

• Tobacco Alcohol and Drug Use Survey

  Self-report survey to assess the frequency of use of multiple drugs: e.g., tobacco, alcohol, marijuana, cocaine, methamphetamine, opioids, etc. as the primary initial tool to assess what substances have been used by participants. This measure produces the number of days in the past year that the participant has used a substance as well as how recently the participant has used a substance.

  12-month and 24-month

Secondary Outcomes (2)

• Age

  at baseline, 12-month and 24-month

• Adverse Life Experiences

  at baseline, 12-month and 24-month

Study Arms (1)

Trier Social Stress Test (TSST)

EXPERIMENTAL

The Trier Social Stress Test for Children (TSST-C) is a social stressor involving story telling in front of two neutral judges, preparation time and a cognitive stressor involving mental arithmetic-counting backward from 1023 by 13s. It is used to elicit physiological stress responses. The TSST-C is administered in 4 parts: an anticipatory stress phase (5 min to prepare the speech); the speech task (5 min), the arithmetic task (5 min), and the recovery phase (up through 40 min post-task).

Behavioral: Trier Social Stress Test

Interventions

Trier Social Stress Test BEHAVIORAL

Psychosocial stress procedure; 5 minutes of public speaking (preceded by 5 minutes of preparation) and 5 minutes of mental arithmetic.

Trier Social Stress Test (TSST)

Eligibility Criteria

• Age: 12 Years - 14 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Male or female
• years old,
• Report symptoms of anxiety
• Understand and sign an assent, and parents will sign a permission and a consent document in English
• Meets study hearing and vision requirements
• Substance use naïve

You may not qualify if:

• Has any foreign metal objects or implants as determined by the safety questionnaires (e.g., bone screws, shunts or body piercing that can't be removed, etc.)
• Has been diagnosed with psychosis or a severe emotional disturbance.
• Has used alcohol, tobacco, or marijuana more than 3 times.
• Is pregnant. Girls who self-report pregnancy may not participate in the stress evaluation or the MRI scan.
• Is taking any medications that directly alter cardiovascular function (e.g., propranolol or other beta blockers).
• Any current or lifetime treatment with antipsychotic medication.
• Has had a head injury that resulted in a loss of consciousness for more than 5 minutes.
• Is planning to get non-removable metal braces.
• Impaired intellectual functioning (full-scale intelligence quotient \<70).
• Past or current history of a clinically significant central nervous system that could confound brain imaging evaluations.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute on Drug Abuse (NIDA): collaborator
• RTI International: collaborator

Study Sites (1)

The University of North Carolina at Chapel Hill School of Medicine

Chapel Hill, North Carolina, 27599, United States

RECRUITING

MeSH Terms

Conditions

Anxiety Disorders; Substance-Related Disorders

Interventions

Psychological Tests

Condition Hierarchy (Ancestors)

Mental Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Behavioral Disciplines and Activities

Study Officials

• Aysenil Belger, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aysenil Belger, PhD

CONTACT

(919)-260-9822‬; aysenil.belger@unc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The Trier Social Stress Test for Children (TSST-C 61)-- a social stressor involving story telling in front of two neutral judges, preparation time and a cognitive stressor involving mental arithmetic-counting backward from 1023 by 13s--will be used to elicit physiological stress responses.

Study Record Dates

• First Submitted: May 8, 2025
• First Posted: May 18, 2025
• Study Start: February 20, 2024
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2030
• Last Updated: May 18, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: The data will become available by 18 months past the study completion date. After uploading, the data will be available in the NDA long term, but must be kept on the NDA for at least three years after the funding period ends.
• Access Criteria: De-identified data will be submitted to the National Institute of Mental Health Data Archive (NDA). To obtain access to the NDA, researchers follow the established procedures within NDA, and the NDA Data Access Committee will determine the approvals for these requests. Access will be given for any legitimate scientific purpose, as determined by NDA Access Committee.

Locations

US (1)