Development of Novel Psychological Assessment Tools and Anxiety Intervention for Phenylketonuria

Development of Novel Psychological Assessment Tools and Anxiety Intervention for PKU: Intervention Trial

While previous PKU intervention research has largely focused on pharmacological treatment of elevated Phe levels, the adaptation of evidence-based psychosocial therapy holds promise for addressing cognitive and psychological symptoms and significantly improving quality of life. Study goals include: (1) to demonstrate the efficacy and feasibility of a short-term skills-based intervention (Show Me FIRST) for anxiety and depression in adolescents with PKU, and (2) to further establish the psychometric validity of novel assessment measures recently developed by the Investigators that utilize ecological momentary assessment (EMA) to capture "in the moment" neurocognitive and psychological function. The Investigators propose to conduct a randomized controlled trial wherein 30 adolescents with PKU will be randomized to either an immediate intervention group or wait-list/delayed intervention group.

Study Overview

• Status: Recruiting
• Conditions: Phenylketonurias
• Intervention / Treatment: Behavioral: Show Me FIRST coping skills intervention

Detailed Description

A sample of 30 adolescents (age 10-17) with PKU and a history of elevated anxiety and/or depression symptomatology will be recruited to participate in a randomized control trial. Following screening and informed consent, participants will be randomized to an immediate intervention group (n=15) or wait-list/delayed intervention group (n=15). Participants will receive the 10-week Show Me First program for treatment of anxiety and depression. Participants will complete extensive psychological and neurocognitive evaluations at three timepoints: Weeks 0, 11, and 22. The assessments and intervention will all be administered remotely via secure videoconference and cell-phone based applications.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shawn Christ; Phone Number: 573-884-8140; Email: christse@missouri.edu

Study Locations

• United States
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Recruiting
      • University of Missouri
      • Contact: Shawn Christ; Phone Number: 573-884-8140; Email: christse@missouri.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Youth 10-17 years old and at least one parent/guardian
• Formal diagnosis of PKU (as confirmed/reported by caregiver): identified by newborn screening with PKU as evidenced by a blood Phe level ≥ 360μmol/L; received treatment within the first 30 days of life.
• Interest in receiving a brief, psychotherapeutic skills program to prevent and treat symptoms of anxiety and/or depression, according to parent- and youth-report
• Located in Missouri, Kansas, or Illinois.

Exclusion Criteria:

• Have significant intellectual disability (IQ<70) or significant expressive or receptive language that would interfere with psychotherapy, according to parent- or youth-report
• Plans to receive non-study psychotherapy during the course of study participation, according to parent- or youth-report
• Plans to change current psychoactive or PKU-related medication during the course of study participation, according to parent- or youth-report
• Have active suicidal ideation that would necessitate immediate treatment or require higher level of care than brief psychotherapy, according to parent- or youth-report

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Immediate Intervention Group	Behavioral: Show Me FIRST coping skills intervention; Show Me FIRST is a flexible, transdiagnostic intervention organized around well-tested principles of youth psychotherapeutic change.
Other: Wait List / Delayed Intervention Group	Behavioral: Show Me FIRST coping skills intervention; Show Me FIRST is a flexible, transdiagnostic intervention organized around well-tested principles of youth psychotherapeutic change.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PROMIS Anxiety & Depression scales	Patient-reported outcome (PRO) measure of anxiety & depression symptoms	Weeks 0, 11, & 22
Test My Brain phone-based EMA cognitive test	Performance-based measure of cognitive skill & attention	Weeks 0, 11, & 22

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Behavior Rating Inventory of Executive Function (BRIEF)	Patient-reported outcome (PRO) measure of everyday symptoms of executive problems	Weeks 0, 11, & 22
Blood Phenylalanine Levels		Weeks 0, 5, 11, 16, & 22
ADHD Rating Scale - 4th version (ADHD-RS-IV)	Patient-reported outcome (PRO) measure of ADHD symptoms	Weeks 0, 11, & 22
Executive Function, Attention, and Speed Symptom Inventory (EASSI) for PKU	Patient-reported outcome (PRO) measure of cognitive symptoms	Weeks 0, 11, & 22
Rey Auditory Verbal Learning Test (Rey AVLT)	Performance-based measure of memory & learning	Weeks 0, 11, & 22
Stop Signal Task (SST)	Performance-based measure of inhibitory ability	Weeks 0, 11, & 22
Revised Children's Anxiety and Depression Scale (RCADS)	Patient-reported outcome (PRO) measure of anxiety & depression symptoms	Weeks 0, 11, & 22
Behavior & Feelings Survey (BFS)	Patient-reported outcome (PRO) measure of internalizing & externalizing problems	Weeks 0, 11, & 22
Adolescent Insomnia Questionnaire (AIQ)	Patient-reported outcome (PRO) measure of sleep problems	Weeks 0, 11, & 22
Global Impression Scale	Patient-reported outcome (PRO) measure of overall symptom severity and improvement	Weeks 0, 11, & 22

Collaborators and Investigators

• Sponsor: University of Missouri-Columbia
• Collaborators: National PKU Alliance

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2024
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: April 30, 2024
• First Submitted That Met QC Criteria: August 16, 2024
• First Posted (Actual): August 19, 2024

Study Record Updates

• Last Update Posted (Actual): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Amino Acid Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Phenylketonurias
• Other Study ID Numbers: 2103266

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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