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Genetic Analysis of the Chiari I Malformation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00004738
Recruitment Status : Completed
First Posted : February 28, 2000
Last Update Posted : July 7, 2022
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Tracking Information
First Submitted Date February 26, 2000
First Posted Date February 28, 2000
Last Update Posted Date July 7, 2022
Actual Study Start Date June 4, 2001
Primary Completion Date Not Provided
Current Primary Outcome Measures
 (submitted: August 11, 2020)
  • Family Pedigree/Genetic Linkage [ Time Frame: ongoing ]
    Establish family pedigrees and undertake genetic linkage analysis that will identify gene loci associated with the Chiari I malformation andunderdevelopment of the bone forming the posterior cranial fossa.
  • Genetic Analysis [ Time Frame: Genetic Analysis ongoing ]
    Genetic analysis of the genomic DNA will be performed with DNA polymorphic markers to identify chromosomal loci linked to the Chiari I and small posterior fossa phenotype.
Original Primary Outcome Measures Not Provided
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Genetic Analysis of the Chiari I Malformation
Official Title Genetic Analysis of the Chiari I Malformation
Brief Summary

The purpose of this study is to better understand the genetic factors related to the Chiari I malformation. In people with this abnormality, the lower part of the skull is smaller than normal. As a result, the lowest part of the brain, called the cerebellar tonsils, protrudes out of the hole at the bottom of the skull into the spinal canal. This study will try to discover the location of the genes responsible for the malformation.

Candidates for this study are: 1) Patients with Chiari I malformation who also have a family member with the abnormality or a family member with syringomyelia (a cyst in the spinal cord that is often associated with the Chiari I malformation). 2) Family members of patients with the Chiari I malformation.

Participants will have a medical history and physical and neurologic examinations. They will undergo magnetic resonance imaging (MRI) of the brain and cervical (neck) spinal cord to measure the size of the head and determine the presence of the Chiari I malformation and syringomyelia. A small blood sample (about 2 tablespoons) will be drawn for DNA studies relating to the Chiari I malformation.

Detailed Description

Objectives: The goal of this study is to establish family pedigrees and undertake genetic linkage analysis that will identify gene loci associated with the Chiari I malformation and underdevelopment of the bone forming the posterior cranial fossa.

Study Population: Patients and family members of patients with the Chiari I malformation. Because the research institutions are located in the United States and Russia, subjects will be recruited predominantly from these countries.

Design: Human subjects will undergo 1) neurologic examinations, 2) head and cervical MRI scans to evaluate for the Chiari I malformation, syringomyelia, and maldevelopment of the posterior fossa, and 3) isolation and analysis of genomic DNA from whole blood for linkage analysis.

Outcome Measures: Pedigrees will be established based on the MRI findings. The Chiari I phenotype will be defined as the caudal portion of the cerebellar tonsils lying greater than or equal to 2 mm below the foramen magnum and underdevelopment of the bone of the posterior fossa will be defined as 1) obliteration of the CSF pathways in the inferior portion of the posterior fossa, 2) posterior fossa volume to supratentorial volume ratio of less than or equal to 15%, or 3) abnormal shortening of the bones of the skull base. Genetic analysis of the genomic DNA will be performed with DNA polymorphic markers to identify chromosomal loci linked to the small posterior fossa phenotype. A lod score of 3.0 (equivalent to 1000:1 odds in favor of linkage) will be taken as proof that the Chiari I gene maps to the same genetic region of the human genome as a given DNA marker.

Study Type Observational
Study Design Observational Model: Family-Based
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Patient with a confirmed diagnosis of Chiari I malformation who has a family member with syringomyelia or Chiari I malformation, or family member of a patient with a confirmed diagnosis of Chiari I malformation.
Condition
  • Syringomyelia
  • Type I Arnold Chiari Malformation
Intervention Not Provided
Study Groups/Cohorts
  • Family Members
    At least 2 family members of a patient with a confirmed diagnosis of Chiari I malformation.
  • Patients
    Patient with a confirmed diagnosis of Chiari I malformation who has a family member with syringomyelia or Chiari I malformation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: July 25, 2020)
152
Original Enrollment
 (submitted: June 23, 2005)
200
Study Completion Date Not Provided
Primary Completion Date Not Provided
Eligibility Criteria
  • INCLUSION CRITERIA:

To be eligible for entry into the study, a candidate must meet the following criteria:

Patient with a confirmed diagnosis of Chiari I malformation who has a family member with syringomyelia or Chiari I malformation, or

Family member of a patient with a confirmed diagnosis of Chiari I malformation, AND

There are at least two family members diagnosed with Chiari I malformation.

If an adult, able to give informed consent; if a minor, has an adult who is legally responsible for the subject and who is able to give consent.

EXCLUSION CRITERIA:

A candidate will be excluded if he/she:

Has a contraindication to MRI scanning.

Is unable to comprehend the risks of the testing.

Is less than one year of age.

Cannot undergo MRI scanning without sedation.

Sex/Gender
Sexes Eligible for Study: All
Ages 1 Year and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Russian Federation,   United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT00004738
Other Study ID Numbers 000089
00-N-0089
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Current Responsible Party National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
Original Responsible Party Not Provided
Current Study Sponsor National Institute of Neurological Disorders and Stroke (NINDS)
Original Study Sponsor Same as current
Collaborators Not Provided
Investigators
Principal Investigator: John D Heiss, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date June 7, 2022