CraniosynostosesNCT04072783
Neurodevelopmental Outcomes in Craniosynostosis Repair
A study testing MRI,DTI, functional MRI in people with Craniosynostoses, run by University of Arkansas at 1 site in United States.
Trial summary
Context: Craniosynostosis is a common craniofacial abnormality which can be associated with various clinical syndromes. Though it has been established that children with craniosynostosis score lower on certain developmental tests, the effect of craniosynostosis and cranioplasty surgery on the neural circuitry and… Read more about this study
- Who is it for?
- Ages Up to 4 yearsHealthy volunteers can take part
- Conditions the study is for
- Craniosynostoses
- What is being tested?
- MRI,DTI, functional MRI
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jul 2021to 31 Dec 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 4 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Up to 500 children, for all subjects, age of initial study entry: one test group between 3-6 months old( endoscopic assisted) , and the other 6-24 months of age ( open CVR) ) once enrolled, children will be included until 4 years of age.
- Diagnosed with craniosynostosis, single or multiple suture
- Babies with craniosynostosis syndrome including but not limited to Pfieffers, Aperts, Crouzons,and Menkes.
- Approximately 60 age-matched controls (3 in each group) not diagnosed with craniosynostosis syndrome, stratified by age groups starting at 3 months, 5 months, 7 months, 9 month 11 months, 13 months, 15 months, 17 months, 19 months, then every 3 months, 22 months, 25 months, 28 months, 31 months, 34 months, 37 months,40 months,43 months,46 months,49 months.
Who cannot join
- Children not meeting the inclusion criteria
- Children with traumatic brain injury, brain cancer, or VP shunt that could affect development.
- Children who have already undergone CVR repair
- Developmentally Normal children who cannot undergo or cannot be still for an awake or asleep non-sedated MRI
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
About this study
Context: Craniosynostosis is a common craniofacial abnormality which can be associated with various clinical syndromes. Though it has been established that children with craniosynostosis score lower on certain developmental tests, the effect of craniosynostosis and cranioplasty surgery on the neural circuitry and brain development is less well known or understood.
Objectives: The purpose of this study is to describe the effect of cranial vault remodeling in children with craniosynostosis on white matter tracts with tractography and Diffusion tensor imaging (DTI), functional MRI, and neurodevelopmental tests, before and after surgery as compared to age-matched controls.
Read more
Study Design: This will be a prospective study of patients diagnosed with craniosynostosis and who are going to have open or endoscopic cranial vault remodeling (CVR).
Study Measures: The study will measure MRI sequences before and after surgery and at set time intervals to quantify the effect of white matter tract maturity. Parallel to this, neurodevelopmental tests will be administered at these same intervals.
Read the detailed description
Craniosynostosis, the premature ossification and fusion of one or more cranial sutures, is a common craniofacial abnormality occurring in 1 of 2,000 live births. 1 2 Craniosynostosis can lead to increased intra-cranial pressure in between 12-50% of those affected which may have delayed neuro developmental implications.
The crucial neurodevelopment occurs in the first years of life and is most rapidly progressing during the first year of life. Premature closure of the cranial sutures decrease the intracranial volume and space available for the rapidly developing brain. Cranial vault remodeling (CVR) is the current standard of care to mitigate any possible developmental delay secondary to craniosynostosis and also improve the head shape. CVR is a combined surgery between the neurosurgeon who takes off the cranial bone/bones, and the craniofacial surgeon who assists and reconstructs the cranium with absorbable plates and screws.
After surgery, although there is no doubt that there is an improvement in head shape, the craniofacial skeleton and the soft tissues, but there is less data, and virtually no functional imaging information available addressing the effect of CVR surgery on the growing brain.
The main objective of this project would be to begin to explore the relationship of CVR and it requisite effects on the growing brain with a cohort of patients who are set to undergo CVR, while performing a battery of neurodevelopmental and imaging studies pre- and post-operatively and compare with normative controls. This is one part of a three-center study collaborating with craniofacial units at Yale University and Wake Forest University in which similar, if not identical protocols will be carried out. We hope that analyses of these data will provide better insight into and greater definition of the effect of CVR and the secondarily available increase in intra-cranial volume on the growing brain in the clinical setting of craniosynostosis.
- Conditions
- Craniosynostoses
- Being tested
- MRI,DTI, functional MRI
- Keywords
- Craniosynostosis, MRI, DTI, Neurodevelopment
- Medical subject headings
- Craniosynostoses
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRI,DTI, functional MRIDiagnostic test
Also called Neurodevelopmental testing, surgery
- Patients will undergo testing with Pre- and and post-surgical MRI. The protocol will be Sagittal T1, Axial inversion recovery, T2, fluid-attenuated inversion recovery, susceptibility weighted image, diffusion weighted images, diffusion tensor imaging, resting state fMRI, sagittal 3D GRE / FFE or 3D T1 VIBE and tractography.
- Once patients are identified, surgery is planned.The standard of care procedures fall into two categories based on age of presentation, clinician judgement and family preference all other things being equal. Both the endoscopic-assisted craniectomy and open CVR are standard of care procedures. Patients self-select into these groups. None of the surgery nor any aspect of it is experimental.
- Patients are routinely examined for neurodevelopment pre- and post-operatively as part of American Cleft Palate Craniofacial Association guidelines.The Vineland Adaptive Behavior Scales are used up to and including age 4.
| Study group | Role | What they receive |
|---|---|---|
| Patients with craniosynostosis | Other | Patients with craniosynostosis will undergo pre - and post-operative imaging studies. The surgery will be performed for these patients as standard of care. They will also be tested fro neurodevelopment. Receives: Diagnostic Test: MRI,DTI, functional MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of Brain Development Via Diagnostic Imaging
Will establish pilot data to establish a normative curve of white-matter tract development in normal children under 4 years of age using (DTI). Fractional anisotropy (FA) (a main DTI parameter sensitive to white matter integrity) maps will be created to achieve a normative "white matter change curve" with from infancy to pre-school age.
Measured: From 2 months age to 4 years of age
Assessment of the Change in White Matter Tract Organization After Cranial Vaut Remodeling Surgery (CVR)
Will quantify the change in white matter tract organization after cranial vault remodeling (CVR) surgery in patients with craniosynostosis by analyzing pre- and post-operative DTI data. This experimental cohort will also be examined in comparison to age-matched controls, pooled with other centers and compared with published data sets of normal babies from the Baby Connectome Project. . The imaging will be repeated at three intervals after surgery leading up to approximately 4 years of age.
Measured: From 2 months age to 4 years of age
Secondary outcomes (1)
Assessment of Neurodevelopmental Test Results in Craniosynostosis Patients
Will assess neurodevelopmental test results in craniosynostosis patients and seek to correlate these findings with white matter tract changes
Measured: From 2 months of age to 4 years of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2019
- Study start8 Jul 2021
- Primary completion31 Dec 2024
- Study completion31 Dec 2024
Why it stopped: Enrollment issues
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for CraniosynostosesStudies of the same condition, open and under way.
- More trials run by University of ArkansasThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Patients with craniosynostosis only
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arkansas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Eylem Ocal, MD, Principal investigator, University of Arkansas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04072783
- Sponsor's protocol ID
- 217610
- Status last verified
- Feb 2026
- First submitted
- 20 Aug 2019
- Last updated
- 22 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurodevelopmental Outcomes in Craniosynostosis Repair
- ClinicalTrials.gov ID
- NCT04072783
- Acronym / sponsor ID
- 217610
- Conditions
- Craniosynostoses
- Keywords
- Craniosynostosis, MRI, DTI, Neurodevelopment
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Enrollment issues
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University of ArkansasUniversity, hospital or other
- Study start
- 8 Jul 2021 (actual)
- Primary completion
- 31 Dec 2024 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 28 Aug 2019 (actual)
- Results
- Posted 22 Apr 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Context: Craniosynostosis is a common craniofacial abnormality which can be associated with various clinical syndromes. Though it has been established that children with craniosynostosis score lower on certain developmental tests, the effect of craniosynostosis and cranioplasty surgery on the neural circuitry and brain development is less well known or understood.
Objectives: The purpose of this study is to describe the effect of cranial vault remodeling in children with craniosynostosis on white matter tracts with tractography and Diffusion tensor imaging (DTI), functional MRI, and neurodevelopmental tests, before and after surgery as compared to age-matched controls.
Study Design: This will be a prospective study of patients diagnosed with craniosynostosis and who are going to have open or endoscopic cranial vault remodeling (CVR).
Study Measures: The study will measure MRI sequences before and after surgery and at set time intervals to quantify the effect of white matter tract maturity. Parallel to this, neurodevelopmental tests will be administered at these same intervals.
Detailed description
Craniosynostosis, the premature ossification and fusion of one or more cranial sutures, is a common craniofacial abnormality occurring in 1 of 2,000 live births. 1 2 Craniosynostosis can lead to increased intra-cranial pressure in between 12-50% of those affected which may have delayed neuro developmental implications.
The crucial neurodevelopment occurs in the first years of life and is most rapidly progressing during the first year of life. Premature closure of the cranial sutures decrease the intracranial volume and space available for the rapidly developing brain. Cranial vault remodeling (CVR) is the current standard of care to mitigate any possible developmental delay secondary to craniosynostosis and also improve the head shape. CVR is a combined surgery between the neurosurgeon who takes off the cranial bone/bones, and the craniofacial surgeon who assists and reconstructs the cranium with absorbable plates and screws.
After surgery, although there is no doubt that there is an improvement in head shape, the craniofacial skeleton and the soft tissues, but there is less data, and virtually no functional imaging information available addressing the effect of CVR surgery on the growing brain.
The main objective of this project would be to begin to explore the relationship of CVR and it requisite effects on the growing brain with a cohort of patients who are set to undergo CVR, while performing a battery of neurodevelopmental and imaging studies pre- and post-operatively and compare with normative controls. This is one part of a three-center study collaborating with craniofacial units at Yale University and Wake Forest University in which similar, if not identical protocols will be carried out. We hope that analyses of these data will provide better insight into and greater definition of the effect of CVR and the secondarily available increase in intra-cranial volume on the growing brain in the clinical setting of craniosynostosis.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patients with craniosynostosis only
| Arm | Type | Receives |
|---|---|---|
| Patients with craniosynostosis | Other | Diagnostic Test: MRI,DTI, functional MRIPatients with craniosynostosis will undergo pre - and post-operative imaging studies. The surgery will be performed for these patients as standard of care. They will also be tested fro neurodevelopment. |
Who may qualify
- Ages
- Up to 4 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Up to 500 children, for all subjects, age of initial study entry: one test group between 3-6 months old( endoscopic assisted) , and the other 6-24 months of age ( open CVR) ) once enrolled, children will be included until 4 years of age.
- Diagnosed with craniosynostosis, single or multiple suture
- Babies with craniosynostosis syndrome including but not limited to Pfieffers, Aperts, Crouzons,and Menkes.
- Approximately 60 age-matched controls (3 in each group) not diagnosed with craniosynostosis syndrome, stratified by age groups starting at 3 months, 5 months, 7 months, 9 month 11 months, 13 months, 15 months, 17 months, 19 months, then every 3 months, 22 months, 25 months, 28 months, 31 months, 34 months, 37 months,40 months,43 months,46 months,49 months.
Key exclusion criteria (4 listed)
- Children not meeting the inclusion criteria
- Children with traumatic brain injury, brain cancer, or VP shunt that could affect development.
- Children who have already undergone CVR repair
- Developmentally Normal children who cannot undergo or cannot be still for an awake or asleep non-sedated MRI
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRI,DTI, functional MRIAlso: Neurodevelopmental testing, surgery1. Patients will undergo testing with Pre- and and post-surgical MRI. The protocol will be Sagittal T1, Axial inversion recovery, T2, fluid-attenuated inversion recovery, susceptibility weighted image, diffusion weighted images, diffusion tensor imaging, resting state fMRI, sagittal 3D GRE / FFE or 3D T1 VIBE and tractography. 2. Once patients are identified, surgery is planned.The standard of care procedures fall into two categories based on age of presentation, clinician judgement and family preference all other things being equal. Both the endoscopic-assisted craniectomy and open CVR are standard of care procedures. Patients self-select into these groups. None of the surgery nor any aspect of it is experimental. 3. Patients are routinely examined for neurodevelopment pre- and post-operatively as part of American Cleft Palate Craniofacial Association guidelines.The Vineland Adaptive Behavior Scales are used up to and including age 4. | Diagnostic test | Patients with craniosynostosis |
Primary outcome
Assessment of Brain Development Via Diagnostic Imaging
Time frame: From 2 months age to 4 years of age
Will establish pilot data to establish a normative curve of white-matter tract development in normal children under 4 years of age using (DTI). Fractional anisotropy (FA) (a main DTI parameter sensitive to white matter integrity) maps will be created to achieve a normative "white matter change curve" with from infancy to pre-school age.
Assessment of the Change in White Matter Tract Organization After Cranial Vaut Remodeling Surgery (CVR)
Time frame: From 2 months age to 4 years of age
Will quantify the change in white matter tract organization after cranial vault remodeling (CVR) surgery in patients with craniosynostosis by analyzing pre- and post-operative DTI data. This experimental cohort will also be examined in comparison to age-matched controls, pooled with other centers and compared with published data sets of normal babies from the Baby Connectome Project. . The imaging will be repeated at three intervals after surgery leading up to approximately 4 years of age.
1 secondary outcome
Assessment of Neurodevelopmental Test Results in Craniosynostosis Patients
Time frame: From 2 months of age to 4 years of age
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Comparing Conservative to Surgical Treatment of Trigonocephaly Craniofacial Surgery in Children With Trigonocephaly: an Observational Cohort Study on Clinical Outcomes, Psychosocial Wellbeing, and Costs
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eylem Ocal, MD principal investigator
University of Arkansas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MRI,DTI, functional MRI in people with Craniosynostoses, run by University of Arkansas at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Apr 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of Brain Development Via Diagnostic Imaging (time frame: From 2 months age to 4 years of age). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2026.