Arnold-Chiari Malformation, Type 1, Chiari Malformation Type I, Syringomyelia, Type I Arnold-Chiari Malformation
Conditions
Brief summary
The purpose of this study is to determine whether a posterior fossa decompression or a posterior fossa decompression with duraplasty results in better patient outcomes with fewer complications and improved quality of life in those who have Chiari malformation type I and syringomyelia.
Detailed description
Participants with Chiari Malformation type I and syringomyelia will be randomized to either have a posterior fossa decompression done with or without duraplasty. The participant will then return to the neurosurgeon's office at the following time points which are consistent with standard of care practice: \< 6 weeks, 3-6 months, and 12 months. At these visits, the clinician will complete a physical exam and the participant will report on the prognosis of symptoms and complete two quality of life questionnaires. A brain and cervical spine MRI will be performed 12 months after the decompression.
Interventions
PROCEDUREPosterior fossa decompression
Planned areas of bone removal from the suboccipital region of the skull and cervical l1 lamina. Then, the constricting epidural band at the level of the foramen magnum is resected.
PROCEDUREDural Augmentation
The dura is opened sharply, exposing the cerebellar tonsils, brainstem, and upper spinal cord. After microsurgical dissection, the dura is sewn closed with a dural graft.
Sponsors
Patient-Centered Outcomes Research Institute
Johns Hopkins All Children's Hospital
Arkansas Children's Hospital Research Institute
Boston Children's Hospital
Children's Healthcare of Atlanta
Dartmouth-Hitchcock Medical Center
Children's Hospital Colorado
Birmingham Children's Hospital
Morgan Stanley Children's Hospital
Phoenix Children's Hospital
Children's Hospital and Health System Foundation, Wisconsin
Children's National Research Institute
Children's Hospital of Philadelphia
Children's Hospital Medical Center, Cincinnati
Columbia University
Gillette Children's Specialty Healthcare
Levine Children's Hospital
Children's Hospital Los Angeles
Ann & Robert H Lurie Children's Hospital of Chicago
Mayo Clinic
Nicklaus Children's Hospital f/k/a Miami Children's Hospital
Medical University of South Carolina Shawn Jenkins Children's Hospital
Oregon Health and Science University
Penn State University
University of Pittsburgh
Primary Children's Hospital
Seattle Children's Hospital
Stanford University
Baylor College of Medicine
The Children's Hospital at OU Medical Center
Nationwide Children's Hospital
University of California
University of Iowa
University of Michigan
The University of Texas Health Science Center, Houston
University of Minnesota
University of Vermont
UVA Children's Hospital
University of Wisconsin, Madison
Vanderbilt University
Wake Forest University
Yale University
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≤21 years old 2. Chiari malformation type I ≥5 mm tonsillar ectopia 3. Syrinx between 3 mm and 6 mm 4. Chiari Severity Index (CSI) classification 1 5. MRI of the brain and cervical and thoracic spine are required prior to surgery and must be available to be shared with the Data Coordinating Center
Exclusion criteria
1. CSI-2 or CSI-3 classification 2. Syrinx \<3 mm and/or ≥6 mm 3. Neuro-imaging demonstrating basilar invagination 4. Clival canal angle \<120° (signs of severe craniovertebral junction disease) 5. Chiari Malformation I + syringomyelia secondary to other pathology (e.g. a tumor) 6. Unable to share pre-decompression MRI of the brain and cervical and thoracic spine 7. Patients who do not wish to participate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With Surgical Complications | less then or equal to 6 months from decompression | The number of participants with complications such as: Cerebrospinal fluid (CSF)-related complications ≤6 months (e.g. CSF leak, pseudomeningocele, aseptic meningitis, infection, hydrocephalus), and the requirement for additional surgery for wound revision or CSF diversion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Aim 2: The Number of Patients With Clinical Improvement | 10-14 months | Number of patients who experienced improvement in clinical or neurological symptoms-such as; headaches, pain, numbness or tingling, nausea/ vomiting, itching, weakness, difficulty swallowing, difficulty sleeping and cranial nerve assessments. |
| Aim 2: The Mean Number of Syrinx Reduction in Millimeters Less Than 24 Months Post Surgery. | 10-14 months | Syrinx regression comparison between posterior fossa decompression surgery and dural augmentation surgery cohorts based on ITT. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Aim 3 : Mean Change in Quality of Life Measurement After Surgery Relative to Baseline. | 10-14 Months from Decompression | Quality of Life (QOL) was assessed using the Chiari Health Index Pediatrics (CHIP), and the Health Utilities-3 (HUI-3). The CHIP is a 5-point response scale. Within the physical symptoms' domain, 5 questions regarding pain severity are alternatively scaled. The Health Utilities Index Mark 3 (HUI3) is a generic status classification system, generalizable in pediatric patients with illness. The HUI3 assesses domains including vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain. We used a non-inferiority approach in the analysis. The score is corrected for missing values and scaled to a range of scores between 0 and 1. An increasing score represents increasing HRQOL. Increase/decrease in the quality of life metric (on a scale from 0-1, with 0 representing no quality of life and 1 representing 100% quality of life). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Posterior Fossa Decompression Surgery The bone is surgically removed from the suboccipital region of the skull and Cervical 1 lamina so the constricting epidural band can be resected
Posterior fossa decompression: Planned areas of bone removal from the suboccipital region of the skull and cervical l1 lamina. Then, the constricting epidural band at the level of the foramen magnum is resected. | 84 |
| Dural Augmentation Surgery The bone is removed from the suboccipital region of the skull and Cervical 1 lamina so the constricting epidural band can be resected. Then, the dura is opened. Microsurgical dissection is performed and the dura is sewn closed.
Dural Augmentation: The dura is opened sharply, exposing the cerebellar tonsils, brainstem, and upper spinal cord. After microsurgical dissection, the dura is sewn closed with a dural graft. | 78 |
| Total | 162 |
Baseline characteristics
| Characteristic | Posterior Fossa Decompression Surgery | Dural Augmentation Surgery | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 80 Participants | 74 Participants | 154 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 4 Participants | 8 Participants |
| Age, Continuous | 9.94 years STANDARD_DEVIATION 5.59 | 10.77 years STANDARD_DEVIATION 5.37 | 10.34 years STANDARD_DEVIATION 5.48 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 9 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 78 Participants | 69 Participants | 147 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 10 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) White | 72 Participants | 59 Participants | 131 Participants |
| Sex: Female, Male Female | 48 Participants | 39 Participants | 87 Participants |
| Sex: Female, Male Male | 36 Participants | 39 Participants | 75 Participants |
| Size of Syringomyelia Syrinx AP Diameter (mm) 3-6 mm | 65 Participants | 37 Participants | 102 Participants |
| Size of Syringomyelia Syrinx AP Diameter (mm) 7-9 mm | 19 Participants | 41 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 84 | 0 / 78 |
| other Total, other adverse events | 0 / 84 | 0 / 78 |
| serious Total, serious adverse events | 0 / 84 | 0 / 78 |
Outcome results
Primary
The Number of Participants With Surgical Complications
The number of participants with complications such as: Cerebrospinal fluid (CSF)-related complications ≤6 months (e.g. CSF leak, pseudomeningocele, aseptic meningitis, infection, hydrocephalus), and the requirement for additional surgery for wound revision or CSF diversion
Time frame: less then or equal to 6 months from decompression
Population: Note: values represent reporting by ITT, i.e. split by randomization, not necessarily treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Posterior Fossa Decompression Surgery | The Number of Participants With Surgical Complications | 8 Participants |
| Dural Augmentation Surgery | The Number of Participants With Surgical Complications | 10 Participants |
Secondary
Aim 2: The Mean Number of Syrinx Reduction in Millimeters Less Than 24 Months Post Surgery.
Syrinx regression comparison between posterior fossa decompression surgery and dural augmentation surgery cohorts based on ITT.
Time frame: 10-14 months
Population: Values represent reporting by ITT not treatment received
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Posterior Fossa Decompression Surgery | Aim 2: The Mean Number of Syrinx Reduction in Millimeters Less Than 24 Months Post Surgery. | 1.06 millimeters | Standard Deviation 1.73 |
| Dural Augmentation Surgery | Aim 2: The Mean Number of Syrinx Reduction in Millimeters Less Than 24 Months Post Surgery. | 3.07 millimeters | Standard Deviation 2.47 |
Secondary
Aim 2: The Number of Patients With Clinical Improvement
Number of patients who experienced improvement in clinical or neurological symptoms-such as; headaches, pain, numbness or tingling, nausea/ vomiting, itching, weakness, difficulty swallowing, difficulty sleeping and cranial nerve assessments.
Time frame: 10-14 months
Population: Note: values represent reporting by ITT, i.e. split by randomization, not necessarily treatment received
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Posterior Fossa Decompression Surgery | Aim 2: The Number of Patients With Clinical Improvement | 43 Participants |
| Dural Augmentation Surgery | Aim 2: The Number of Patients With Clinical Improvement | 43 Participants |
Other Pre-specified
Aim 3 : Mean Change in Quality of Life Measurement After Surgery Relative to Baseline.
Quality of Life (QOL) was assessed using the Chiari Health Index Pediatrics (CHIP), and the Health Utilities-3 (HUI-3). The CHIP is a 5-point response scale. Within the physical symptoms' domain, 5 questions regarding pain severity are alternatively scaled. The Health Utilities Index Mark 3 (HUI3) is a generic status classification system, generalizable in pediatric patients with illness. The HUI3 assesses domains including vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain. We used a non-inferiority approach in the analysis. The score is corrected for missing values and scaled to a range of scores between 0 and 1. An increasing score represents increasing HRQOL. Increase/decrease in the quality of life metric (on a scale from 0-1, with 0 representing no quality of life and 1 representing 100% quality of life).
Time frame: 10-14 Months from Decompression
Population: Note: values represent reporting by ITT, i.e. split by randomization, not necessarily treatment received
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Posterior Fossa Decompression Surgery | Aim 3 : Mean Change in Quality of Life Measurement After Surgery Relative to Baseline. | 0.02 score on a scale | Standard Deviation 0.16 |
| Dural Augmentation Surgery | Aim 3 : Mean Change in Quality of Life Measurement After Surgery Relative to Baseline. | 0.04 score on a scale | Standard Deviation 0.17 |