TIDES 2.0: Prevalence and Longitudinal Course of Depression, Anxiety, and Behavior Problems in Children With Cystic Fibrosis Under 12 Years of Age (TIDES 2)

This is a longitudinal, observational epidemiological study designed to estimate the prevalence of depression, anxiety, and behavior problems in children ages 18 months through 11 years with cystic fibrosis (CF).

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis (CF)

Detailed Description

Integration of mental health (MH) screening and treatment into cystic fibrosis (CF) care represents over 10 years of research and clinical progress, driven by elevated rates of depression and anxiety in the International Depression Epidemiological Study, MH guidelines, and CF Foundation implementation support to screen adolescents and adults in all CF Centers. Benefits of screening include earlier identification, greater access to care, reduced stigma, and positive uptake from the CF community.

However, TIDES did not include children with CF under 12 years. Depression and anxiety have increased dramatically in young children, with new guidelines for MH screening of children in primary care. Given the pediatric MH crisis and the widespread adoption of cystic fibrosis fibrosis transmembrane conductance regulator (CFTR) modulator therapy, which have been associated with adverse events, there is an urgent need to gather MH data in children with CF <12 years. Thus, the goals of this study are to evaluate the national, longitudinal prevalence of depression, anxiety, and behavior problems in children with CF 18 months through 11 years, evaluate and compare the performance of two widely used brief screeners (criterion validity, sensitivity, specificity) to identify the optimal measures for this population, and characterize neuropsychiatric adverse events (AEs) associated with CFTR modulator therapy in this age group. Purposive randomized sampling will be used to recruit 600 children (half 18 mos.-5 yrs. and half 6-11 yrs.) at 16 CF Centers across the US. This study will estimate the prevalence of children above the clinical cut-score on each symptom domain (depression, anxiety, behavior problems) and evaluate their longitudinal course and predictors. Rigorous mixed methods will be used to describe any potential AEs perceived by parents or children to be associated with CFTR modulator therapy. This study will provide the groundwork to extend mental health screening and care to younger children with CF.

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

• Study Contact: Name: Beth A Smith, MD; Phone Number: 716-898-5940; Email: balucas@buffalo.edu
• Study Contact Backup: Name: Minu Mohan, MPH; Email: minuponn@buffalo.edu

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • Children's Hospital of Orange County
      • Contact: Adrianne Alpern, PhD; Phone Number: 657-767-2730; Email: aalpern@choc.org
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Children's Hospital Colorado
      • Contact: Emily Muther, PhD; Phone Number: 720- 777-3257; Email: Emily.Muther@childrenscolorado.org
  • Florida
    • Hollywood, Florida, United States, 33021
      • Recruiting
      • Joe DiMaggio
      • Contact: Alexandra L Quittner, PhD; Phone Number: 305-992-2411; Email: aquittner@mhs.net
    • Orlando, Florida, United States, 32827
      • Recruiting
      • Nemours Foundation
      • Contact: David Fedele, PhD; Phone Number: 352-294-5765; Email: David.Fedele@nemours.org
  • Indiana
    • Bloomington, Indiana, United States, 47405
      • Recruiting
      • Indiana University
      • Contact: Emma M Tillman, PhD, PharmD; Phone Number: (317) 274-2797; Email: emtillma@iu.edu
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Anna M Georgiopoulos, MD; Phone Number: 617-724 -6300; Email: AGEORGIOPOULOS@mgh.harvard.edu
  • New York
    • Buffalo, New York, United States, 14215
      • Recruiting
      • University at Buffalo
      • Contact: Danielle M Goetz, MD; Phone Number: 716-323-0110; Email: dgoetz@upa.chob.edu
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • University of North Carolina School of Medicine
      • Contact: Mary Beth Prieur, PhD; Phone Number: 919-843-3209; Email: mary_grimley@med.unc.edu
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital Medical Center
      • Contact: Stephanie Filigno, PhD; Phone Number: 513-636-7793; Email: stephanie.filigno@cchmc.org
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Active, not recruiting
      • Brown University Health
  • Texas
    • Plano, Texas, United States, 75235
      • Recruiting
      • Ut Southwestern
      • Contact: Meghna Sathe, MD; Phone Number: 214-456-8000; Email: meghna.sathe@utsouthwestern.edu
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Recruiting
      • Children's Hospital of Richmond at Virginia Commonwealth University
      • Contact: Michael S Schechter, MD, MPH; Phone Number: 410- 550-7755; Email: michael.schechter@vcuhealth.org
  • Washington
    • Seattle, Washington, United States, 98105
      • Recruiting
      • Seattle Children's Hospital
      • Contact: Freda Liu, PhD; Phone Number: 206-987-3295; Email: freda.liu@seattlechildrens.org

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Children with Cystic Fibrosis between 18 months and 11 years

Description

Inclusion Criteria:

1. Child with a diagnosis of Cystic fibrosis (CF) actively followed by the CF care team at a participating site
2. Child is age 18 months thru 11 years
3. English and/or Spanish speaking
4. Parent/legal guardian willing and able to give informed consent, and for minor participants ages 7 thru 11 years able to give assent.

Exclusion Criteria:

• Unable or unwilling to participate in study procedures, or at Site PI discretion.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Preschool / Early Childhood Group (18 mos - 5 years); 300 children with CF and their parents will be recruited. This cohort will help identify early signs of internalizing and externalizing behaviors, attention-related concerns, and the impact of CF treatments on psychosocial health. Children in this cohort may also be identified for participation in Aim 3 if they are on or eligible for modulator therapy.
School-Age Group (6 - 11 years); 300 children with CF and their parents will be recruited. Includes school-aged children who can self-report their emotional and behavioral health, beginning at age 8 years. This group will be assessed for emerging mental health symptoms, cognitive development, and procedural anxiety related to CF treatments. Children in this cohort may also be identified for participation in Aim 3 if they are on or eligible for modulator therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of depression, anxiety, and behavioral problems in children with cystic fibrosis	Estimate the national prevalence of depression, anxiety, and behavioral problems among children with cystic fibrosis aged 18 months through 11 years using the Behavior Assessment System for Children, Third Edition (BASC-3). At the baseline assessment (Time 1), parents complete the age-appropriate BASC-3 Parent Rating Scale, and children aged 8-11 years complete the BASC-3 Self-Report of Personality. BASC-3 classifications of emotional and behavioral symptoms will be used to estimate the prevalence of clinically significant symptoms.	07/01/2024 - 06/30/2028

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic performance of brief behavioral and mental health screening instruments	Evaluate the diagnostic accuracy and clinical utility of the Pediatric Symptom Checklist (PSC-Preschool, PSC-17, and PSC-Y-17) and PROMIS short forms for anxiety, depressive symptoms, anger/irritability, sleep disturbance, cognitive functioning, flexibility, and persistence by comparing their performance with BASC-3 at baseline.	07/01/2024 - 06/30/2028
Longitudinal changes in child mental health symptoms	Assess changes in parent-reported and child self-reported mental health symptoms over three study assessments using PSC and PROMIS measures. BASC-3 is administered only at the first assessment.	07/01/2024 - 06/30/2028
Cystic fibrosis-specific health-related quality of life	Assess CF-specific health-related quality of life using age-appropriate versions of the Cystic Fibrosis Questionnaire-Revised (CFQ-R). Parent-proxy and child self-report versions are administered according to participant age, with the Preschool Pictorial CFQ-R administered once for eligible children.	07/01/2024 - 06/30/2028
Parent symptoms of depression and anxiety	Assess parent mental health using the Patient Health Questionnaire-8 (PHQ-8) and Generalized Anxiety Disorder-7 (GAD-7) at each assessment.	07/01/2024 - 06/30/2028
Neuropsychiatric symptoms associated with CFTR modulator therapy	Evaluate parent-reported new or worsening neuropsychiatric symptoms following initiation of elexacaftor/tezacaftor/ivacaftor (ETI) or vanzacaftor/tezacaftor/deutivacaftor (VTD) using the CFTR Modulator Survey. Symptoms include anxiety, depression, attention problems, behavioral dysregulation, irritability, and sleep disturbance. The Modified Naranjo Scale will be used to assess the likelihood that reported symptoms are related to CFTR modulator therapy.	07/01/2024 - 06/30/2028
Qualitative experiences related to CFTR modulator-associated neuropsychiatric symptoms	Conduct semi-structured qualitative interviews with a purposive sample of parents reporting worsening neuropsychiatric symptoms following CFTR modulator initiation or non-initiation because of mental health concerns. Eligible school-aged children may also participate. Interview transcripts will undergo thematic analysis.	07/01/2024 - 06/30/2028

Collaborators and Investigators

• Sponsor: State University of New York at Buffalo
• Collaborators: Brown University; Cystic Fibrosis Foundation

Publications and helpful links

General Publications

• Quittner AL, Goldbeck L, Abbott J, Duff A, Lambrecht P, Sole A, Tibosch MM, Bergsten Brucefors A, Yuksel H, Catastini P, Blackwell L, Barker D. Prevalence of depression and anxiety in patients with cystic fibrosis and parent caregivers: results of The International Depression Epidemiological Study across nine countries. Thorax. 2014 Dec;69(12):1090-7. doi: 10.1136/thoraxjnl-2014-205983. Epub 2014 Sep 21.

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2025
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: June 8, 2025
• First Submitted That Met QC Criteria: June 29, 2025
• First Posted (Actual): July 2, 2025

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: July 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Depression; Anxiety; Children; Cystic Fibrosis; CFTR modulators; Mental health screening; Neuropsychiatric adverse events
• Additional Relevant MeSH Terms: Mental Disorders; Genetic Diseases, Inborn; Behavioral Symptoms; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Behavior; Anxiety Disorders; Depression; Cystic Fibrosis
• Other Study ID Numbers: STUDY00008868; SMITH 24A0 (Other Grant/Funding Number: Cystic Fibrosis Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

An application process will be established for external data requests. Initially, data access will be granted upon request by Brown University Health (BUH), with full public access only after a defined period following study completion.

Beyond academic publications, BUH will contribute to the creation of publicly available study summaries, ensuring that key findings are accessible to the CF community, healthcare providers, and patient advocacy groups.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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