Craniofacial Microsomia: Longitudinal Outcomes in Children Pre-Kindergarten (CLOCK) (CLOCK)

This study is a multi-center, longitudinal cohort study of 125 infants with craniofacial microsomia (CFM) and 100 infants without craniofacial anomalies. Participants will undergo a series of evaluations between 0-3 years of age to comprehensively evaluate the developmental status of infants and toddlers with CFM. This research design will also explore specific pathways by which CFM may lead to certain outcomes. Specifically, the study explores (1) the longitudinal relations between facial asymmetry and emotion-related facial movements and socialization; and (2) associations among ear malformations, hearing and speech deficits and cognitive outcomes. Results of this research will ultimately lead to future investigations that assess new interventions and corresponding changes in current standards of care for children with CFM.

Study Overview

• Status: Completed
• Conditions: Craniofacial Microsomia; Goldenhar Syndrome; Microtia; Hemifacial Microsomia; Oculo-Auriculo-Vertebral-Syndrome

• Study Type: Observational
• Enrollment (Actual): 417

Contacts and Locations

• Study Contact: Name: Amber Sand; Phone Number: 206-884-1844; Email: amber.sand@seattlechildrens.org
• Study Contact Backup: Name: Sharman Conner; Phone Number: 206-887-4924; Email: sharman.conner@seattlechildrens.org

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
  • Illinois
    • Chicago, Illinois, United States, 60607
      • University of Illinois at Chicago
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 90027
      • Children's Hospital of Philadelphia
  • Washington
    • Seattle, Washington, United States, 98101
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 2 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Children with and without craniofacial microsomia will be drawn from outpatient clinics, medical centers, and local pediatric practices near performance sites and local pediatric practices. Cases will be approached in their first 24 months by either a member of their craniofacial team, a member of the CLOCK study team, or one of their treating providers. Cases may find out about the study through ClinicalTrials.gov. Controls will initially be approached through a treating provider, a member of the CLOCK team, or through an announcement about the study.

Description

We are currently looking to enroll children with craniofacial microsomia through ClinicalTrials.gov

Inclusion Criteria:

Children with Craniofacial Microsomia:

1. Male or female infant participant is between 12 months and 24 months of age, or corrected age (for some infants born prior to their due date).

2. Infant participant has diagnosis of at least one of the following conditions:

   • Microtia
   • Anotia
   • Facial asymmetry AND Preauricular tag(s)
   • Facial asymmetry AND Facial tag(s)
   • Facial asymmetry AND Epibulbar dermoid
   • Facial asymmetry AND Macrostomia (i.e., lateral cleft)
   • Preauricular tag AND Epibulbar dermoid
   • Preauricular tag AND Macrostomia
   • Facial tag AND Epibulbar dermoid
   • Macrostomia AND Epibulbar dermoid
3. Infant participant has been diagnosed by a regional craniofacial team.
4. Legal guardian will provide written parental permission and informed consent prior to participation in study.
5. Legal guardian is willing to comply with all study procedures and be available for the duration of the study through Time 3.

Parents of Children with Craniofacial Microsomia:

• able to provide written consent for study participation,
• willing to comply with all study procedures and
• interested in participating in the entire study through Time 3.

Exclusion Criteria:

Children with Craniofacial Microsomia:

1. Subject is diagnosed with a known syndrome that involves microtia and/or underdevelopment of the jaw (Townes-Brocks, Treacher Collins, branchiootorenal, Nager, or Miller syndromes).
2. Subject has abnormal chromosome studies (karyotype)
3. Subject has a major medical or neurological condition that prevents participation in the study (e.g., cancer, cerebral palsy) at time of recruitment
4. Subject was born before 34 weeks estimated gestational age
5. Anything that would place the subject at increased risk or preclude the subject's full compliance with or completion of the study.
6. Sibling already participating in the CLOCK study
7. Subject's consenting parent does not speak English or Spanish

Parents of Children with Craniofacial Microsomia

1. Anything that would preclude the subject's full compliance with or completion of the study.
2. Subject does not speak English or Spanish

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
Children with Craniofacial Microsomia; 125 children with craniofacial microsomia will be asked to come in for two study visits - when they are about 12 months old and again when they are about 36 months old. Procedures for children at the first visit include: assessment of development, video, photographs, and a hearing evaluation. Procedures for the final study visit include: assessment of development, photographs (2D & 3D), video, saliva sample, hearing evaluation, speech assessment.
Children without Craniofacial Microsomia; Please note: we are not recruiting this group through ClinicalTrials.gov 100 children without craniofacial microsomia will be asked to come in for two study visits - when they are about 12 months old and again when they are about 36 months old. Procedures for the first visit include: assessment of development, video, and photographs. Procedures for the final study visit include: assessment of development, photographs (2D & 3D), video, and speech assessment.
Parents of Children with Craniofacial Microsomia; 125-250 parents of children with craniofacial microsomia will be asked to complete three visits - when their child is about 12 months old, 24 months old, and 36 months old. Parents will be asked to complete an interview at the first visit. The second visit consists of a telephone interview where parents will be asked about their child's hearing and health history. At the final study visit, parents will be asked to complete more questionnaires, have their picture taken, and donate saliva.
Parents of Children without Craniofacial Microsomia; Please note: we are not recruiting this group through ClinicalTrials.gov 100 parents of children without craniofacial microsomia will be asked to complete three visits - when their child is about 12 months old, 24 months old, and 36 months old. Parents will be asked to complete an interview at the first visit. The second visit consists of a telephone interview where parents will be asked about their child's hearing and health history. At the final study visit, parents will be asked to complete questionnaires and an interview.
Teacher/Day Care Provider; When the children participants are around 36 months old, we will ask parents for permission to contact their child's teacher/day care provider. We would like the teacher/day care provider to fill out a questionnaire.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurodevelopmental Outcome Measures	BSID-III Cognitive Index	T1 study visit (12-14 months of age)
Phenotypic Assessments	2D photographs and video	T1 study visit (12-14 months of age)
Phenotypic Assessments	Medical and Surgical History	T2 study visit (~24 months)
Neurodevelopmental Outcome Measures	BSID-III Cognitive Index	T3 study visit (~36 months)
Neurodevelopmental Outcome Measures	BSID-III Fine & Gross Motor	T1 study visit (12-14 months of age)
Neurodevelopmental Outcome Measures	PLS-V Auditory Comprehension	T1 study visit (12-14 months of age)
Neurodevelopmental Outcome Measures	PLS-V Expressive Language	T1 study visit (12-14 months of age)
Phenotypic Assessments Phenotypic Assessments Phenotypic Assessments	3D photographs,	T1 study visit (12-14 months of age)
Phenotypic Assessments	Medical and Surgical History	T1 study visit (12-14 months of age)
Phenotypic Assessments	Medical/dental chart abstraction	T1 study visit (12-14 months of age)
Phenotypic Assessments	IT-MAIS: Auditory Assessment	T1 study visit (12-14 months of age)
Phenotypic Assessments	OMENS rating from 2D images	T1 study visit (12-14 months of age)
Phenotypic Assessments	Baby FACS observational protocol	T1 study visit (12-14 months of age)
Phenotypic Assessments	Clinical Hearing Test	T1 study visit (12-14 months of age)
Phenotypic Assessments	IT-MAIS: Auditory Assessment	T2 study visit (~24 months)
Neurodevelopmental Outcome Measures	BSID-III Fine & Gross Motor	T3 study visit (~36 months)
Neurodevelopmental Outcome Measures	Leiter-R Brief IQ	T3 study visit (~36 months)
Neurodevelopmental Outcome Measures	Leiter-R Forward Memory	T3 study visit (~36 months)
Neurodevelopmental Outcome Measures	Leiter-R Sustained Attention	T3 study visit (~36 months)
Neurodevelopmental Outcome Measures	Leiter-R Associated Pairs	T3 study visit (~36 months)
Neurodevelopmental Outcome Measures	Leiter-R Matching	T3 study visit (~36 months)
Neurodevelopmental Outcome Measures	Leiter-R Picture Context	T3 study visit (~36 months)
Neurodevelopmental Outcome Measures	PLS-V Auditory Comprehension	T3 study visit (~36 months)
Neurodevelopmental Outcome Measures	PLS-V Expressive Language	T3 study visit (~36 months)
Neurodevelopmental Outcome Measures	NEPSY-II Phonological Processing	T3 study visit (~36 months)
Neurodevelopmental Outcome Measures	ITSEA Parent	T3 study visit (~36 months)
Neurodevelopmental Outcome Measures	ITSEA Teacher	T3 study visit (~36 months)
Neurodevelopmental Outcome Measures	Goldman-Fristoe Test of Articulation (GFTA-2)	T3 study visit (~36 months)
Phenotypic Assessments	2D photographs and video	T3 study visit (~36 months)
Phenotypic Assessments	3D photographs	T3 study visit (~36 months)
Phenotypic Assessments	Medical and Surgical History	T3 study visit (~36 months)
Phenotypic Assessments	Medical/dental chart abstraction	T3 study visit (~36 months)
Phenotypic Assessments	IT-MAIS: Auditory Assessment	T3 study visit (~36 months)
Phenotypic Assessments	OMENS rating from 2D images	T3 study visit (~36 months)
Phenotypic Assessments	Hearing Evaluation	T3 study visit (~36 months)
Phenotypic Assessments	Interview on willingness for future study	T3 study visit (~36 months)
Phenotypic Assessments	DNA collection (DNA)	T3 study visit (~36 months)

Collaborators and Investigators

• Sponsor: Seattle Children's Hospital
• Collaborators: Children's Hospital of Philadelphia; Northwestern University; New York University; University of Pittsburgh; University of Illinois at Chicago; National Institute of Dental and Craniofacial Research (NIDCR); University of Washington; Children's Hospital Los Angeles; University of North Carolina
• Investigators: Principal Investigator: Carrie L Heike, MD, MS, Seattle Children's Hospital; Principal Investigator: Matthew L Speltz, PhD, Seattle Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2013
• Primary Completion (Actual): August 31, 2019
• Study Completion (Actual): August 31, 2019

Study Registration Dates

• First Submitted: August 19, 2014
• First Submitted That Met QC Criteria: August 21, 2014
• First Posted (Estimated): August 25, 2014

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: cognition; toddler; infant; baby; neurodevelopment; CFM; facial asymmetry; skin tag; facial tag; missing ear; small ear; anotia; microtia; epibulbar dermoid; coloboma; macrostomia; lateral cleft; socialization
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Congenital Abnormalities; Musculoskeletal Diseases; Otorhinolaryngologic Diseases; Ear Diseases; Bone Diseases; Fetal Diseases; Pregnancy Complications; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Growth Disorders; Bone Diseases, Developmental; Mandibulofacial Dysostosis; Craniofacial Dysostosis; Dysostoses; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Syndrome; Fetal Growth Retardation; Goldenhar Syndrome; Congenital Microtia
• Other Study ID Numbers: NIDCR: 13-002-E; R01DE022438-01 (U.S. NIH Grant/Contract)