Chromosome 18 Clinical Research Center

Growth Hormone Deficiency Clinical Trial

— Chromosome18  

Official title:

The Chromosome 18 Clinical Research Center

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00227253
• Other study ID #: Chromosome 18
• Secondary ID: 5M01RR001346
• Status: Recruiting
• Start date: September 1993
• Est. completion date: December 2040

Study information

• Verified date: November 2023
• Source: The University of Texas Health Science Center at San Antonio
• Contact: Jannine D. Cody, Ph.D.
• Phone: 210-567-9220
• Email: cody[@]uthscsa.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Our vision, that of the researchers at the University of Texas Health Science Center at San Antonio, is that every person with a chromosome 18 abnormality will have an autonomous and healthy life. Our mission is to provide families affected by chromosome 18 abnormalities with comprehensive medical and educational information. Our goals are to provide definitive medical and education resources for the families of individuals with chromosome 18 abnormalities; perform and facilitate groundbreaking clinical and basic research relating to the syndromes of chromosome 18; and to provide treatments to help these individuals overcome the effects of their chromosome abnormality.

Description:

Protocol Summary: The hypotheses are: 1. growth hormone (GH) deficiency in children with chromosome 18 deletions is accompanied by cognitive and microstructural abnormalities of the brain that can be ameliorated by GH treatment; and 2. the physical and behavioral findings in individuals with abnormalities of chromosome 18 are due to the genes that present in a non-diploid number. Therefore, correlation of the physical and behavioral findings with the extent of the deletion will help identify the genes involved. An understanding of the molecular mechanisms of the phenotype will provide the insight necessary to devise appropriate therapies. Our goals are: 1. to be the international medical and education resource for the families of individuals with chromosome 18 abnormalities; 2. to perform and facilitate both clinical and basic research relating to the disorders of chromosome 18; and 3. to devise treatments to help these individuals overcome the negative effects of their chromosome abnormality. To attain these goals, the study has the following specific aims: 1. perform genotypic molecular analysis on the DNA of the subjects and their biological parents to determine the genotype of the affected individual; 2. gather comprehensive clinical data on individuals with chromosome 18 abnormalities including: 1. determination of growth hormone levels; 2. measurement of corticotrophin, thyroid and sex hormones; 3. psychiatric and neuropsychological evaluations; 4. audiology and ENT testing; 5. brain MRI scan; 6. genetic dysmorphology examination; 7. neurology exam; 8. dental exam; 9. speech pathology evaluation; 10. gastrointestinal exam; 11. orthopedic exam; 12. ophthalmology exam. The phenotypical assessment will be longitudinal; therefore, the participants will have a wide age range. This extensive range plus the fact that some participants will be assessed multiple times means that not all components of the clinical studies will be appropriate for every subject at every visit.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4000
• Est. completion date: December 2040
• Est. primary completion date: December 2040
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Must have a confirmed diagnosis of Chromosome 18 or be the parent/guardian of a child with Chromosome 18
• Subject must be at least one year of age to participate in the clinical examination aspect of the study (due to issues of venous access and blood volume required to complete studies)
• General health status: good

Exclusion Criteria:

• Pregnant women
• Dead fetuses
• Prisoners
• Non-viable neonates or neonates of uncertain viability

Related Conditions & MeSH terms

• Chromosome Aberrations
• Growth Hormone Deficiency
• Hypomyelination

Intervention

Procedure:
• Determination of growth hormone status
Growth hormone stimulating testing using Arginine and Clonidine, Corticotrophin releasing hormone stimulation test
• Measurement of growth, thyroid and sex hormone levels
Gonadotrophin releasing hormone stimulation test Thyroid testing - T4, TSH, T3 uptake, and anti-thyroidal antibodies baseline sample - no medication administered
• Behavior and neuropsychometric evaluations
evaluation by neuropsychologist, standardized testing geared to study participant's age, abilities and past medical history
• Audiological and ear, nose and throat examination
neurotological exam, behavioral audiometry, immittance audiometry, assessment of the function of the inner ear using otoacoustic emissions, Auditory brain responses
• Magnetic resonance imaging of the brain
MRI of the brain - standard clinical procedure
• Dysmorphology evaluation
Genetic evaluation with picture and measurements, physical exam
• Neurology examination
physical examination including observation of balance, coordination and reflexes.
• Dental evaluation
Visual detal inspection with panorex X-ray of the entire mouth
• Speech pathology evaluation
Standardized speech & language tests and naturalistic assessment procedures.
• Psychiatric evaluation
Psychiatric interview about history of psychiatric and medical illnesses, family psychiatric and medical history, demographic info also obtained
• Orthopedic evaluation
Physical exam by orthopedic surgeon and a dysplasia series of radiographs including AP and lateral radiographics of the feet, APs of the knees, pelvis, thoracic lumbar spine and chest, laterals of thoracic lumbar and cervical spine, lateral of the skull, AP and lateral of the forearm, bone age evaluation with radiograph of left hand
• Ophthalmologic evaluation
exam will determine visual acuity using one of the following: Snellen chart, Allen acuity, target acuity, optokinetic nystagmus (OKN), or Teller acuity depending on study participants ability level. Motility/alignment will also be determined using cover/uncover test. Pupils examined using slit lamp. Dilated fundus exam and cycloplegic refraction which will require dilating drops in both eyes. Cyclogen 1% and NeuSynephrine 2.5% are using. In children less than 6 months old, less potent mydriatrics and cycloplegics are used Cyclogel 0.5% or Tropicamide 1%. Intraocular pressure will be measured in adults and cooperative teens using applanation tonometry. A topical anesthetic will be used to perform this measurement.
• Gastrointestinal evaluation
physical exam and medical history by board certified gastroenterologist.

Locations

Country	Name	City	State
United States	University Health Systems Hospital	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
The University of Texas Health Science Center at San Antonio	National Center for Research Resources (NCRR)

Country where clinical trial is conducted

United States, 

References & Publications (25)

Brkanac Z, Cody JD, Leach RJ, DuPont BR. Identification of cryptic rearrangements in patients with 18q- deletion syndrome. Am J Hum Genet. 1998 Jun;62(6):1500-6. doi: 10.1086/301854. — View Citation

Carter E, Heard P, Hasi M, Soileau B, Sebold C, Hale DE, Cody JD. Ring 18 molecular assessment and clinical consequences. Am J Med Genet A. 2015 Jan;167A(1):54-63. doi: 10.1002/ajmg.a.36822. Epub 2014 Oct 22. — View Citation

Cody JD, Ghidoni PD, DuPont BR, Hale DE, Hilsenbeck SG, Stratton RF, Hoffman DS, Muller S, Schaub RL, Leach RJ, Kaye CI. Congenital anomalies and anthropometry of 42 individuals with deletions of chromosome 18q. Am J Med Genet. 1999 Aug 27;85(5):455-62. d — View Citation

Cody JD, Hale DE, Brkanac Z, Kaye CI, Leach RJ. Growth hormone insufficiency associated with haploinsufficiency at 18q23. Am J Med Genet. 1997 Sep 5;71(4):420-5. — View Citation

Cody JD, Hale DE. Making chromosome abnormalities treatable conditions. Am J Med Genet C Semin Med Genet. 2015 Sep;169(3):209-15. doi: 10.1002/ajmg.c.31447. — View Citation

Cody JD, Hale DE. Precision in phenotyping and genotyping. Am J Med Genet A. 2004 Dec 15;131(3):313. doi: 10.1002/ajmg.a.30263. No abstract available. — View Citation

Cody JD, Hasi M, Soileau B, Heard P, Carter E, Sebold C, O'Donnell L, Perry B, Stratton RF, Hale DE. Establishing a reference group for distal 18q-: clinical description and molecular basis. Hum Genet. 2014 Feb;133(2):199-209. doi: 10.1007/s00439-013-1364 — View Citation

Cody JD, Pierce JF, Brkanac Z, Plaetke R, Ghidoni PD, Kaye CI, Leach RJ. Preferential loss of the paternal alleles in the 18q- syndrome. Am J Med Genet. 1997 Mar 31;69(3):280-6. doi: 10.1002/(sici)1096-8628(19970331)69:33.0.co;2-n. — View Citation

Cody JD, Reveles XT, Hale DE, Lehman D, Coon H, Leach RJ. Haplosufficiency of the melancortin-4 receptor gene in individuals with deletions of 18q. Hum Genet. 1999 Nov;105(5):424-7. doi: 10.1007/s004390051125. — View Citation

Cody JD, Sebold C, Heard P, Carter E, Soileau B, Hasi-Zogaj M, Hill A, Rupert D, Perry B, O'Donnell L, Gelfond J, Lancaster J, Fox PT, Hale DE. Consequences of chromsome18q deletions. Am J Med Genet C Semin Med Genet. 2015 Sep;169(3):265-80. doi: 10.1002/ — View Citation

Cody JD, Semrud-Clikeman M, Hardies LJ, Lancaster J, Ghidoni PD, Schaub RL, Thompson NM, Wells L, Cornell JE, Love TM, Fox PT, Leach RJ, Kaye CI, Hale DE. Growth hormone benefits children with 18q deletions. Am J Med Genet A. 2005 Aug 15;137(1):9-15. doi: — View Citation

Gay CT, Hardies LJ, Rauch RA, Lancaster JL, Plaetke R, DuPont BR, Cody JD, Cornell JE, Herndon RC, Ghidoni PD, Schiff JM, Kaye CI, Leach RJ, Fox PT. Magnetic resonance imaging demonstrates incomplete myelination in 18q- syndrome: evidence for myelin basic — View Citation

Ghidoni PD, Hale DE, Cody JD, Gay CT, Thompson NM, McClure EB, Danney MM, Leach RJ, Kaye CI. Growth hormone deficiency associated in the 18q deletion syndrome. Am J Med Genet. 1997 Mar 3;69(1):7-12. doi: 10.1002/(sici)1096-8628(19970303)69:13.0.co;2-p. — View Citation

Gunn SR, Mohammed M, Reveles XT, Viskochil DH, Palumbos JC, Johnson-Pais TL, Hale DE, Lancaster JL, Hardies LJ, Boespflug-Tanguy O, Cody JD, Leach RJ. Molecular characterization of a patient with central nervous system dysmyelination and cryptic unbalance — View Citation

Hale DE, Cody JD, Baillargeon J, Schaub R, Danney MM, Leach RJ. The spectrum of growth abnormalities in children with 18q deletions. J Clin Endocrinol Metab. 2000 Dec;85(12):4450-4. doi: 10.1210/jcem.85.12.7016. — View Citation

Hasi-Zogaj M, Sebold C, Heard P, Carter E, Soileau B, Hill A, Rupert D, Perry B, Atkinson S, O'Donnell L, Gelfond J, Lancaster J, Fox PT, Hale DE, Cody JD. A review of 18p deletions. Am J Med Genet C Semin Med Genet. 2015 Sep;169(3):251-64. doi: 10.1002/a — View Citation

Hermesch CB, Cody JT, Cody JD. Dental caries history in nine children with chromosome 18p deletion syndrome. Spec Care Dentist. 2000 Mar-Apr;20(2):53-5. doi: 10.1111/j.1754-4505.2000.tb01143.x. — View Citation

Keppler-Noreuil KM, Carroll AJ, Finley SC, Descartes M, Cody JD, DuPont BR, Gay CT, Leach RJ. Chromosome 18q paracentric inversion in a family with mental retardation and hearing loss. Am J Med Genet. 1998 Apr 13;76(5):372-8. doi: 10.1002/(sici)1096-8628( — View Citation

Kochunov P, Lancaster J, Hardies J, Thompson PM, Woods RP, Cody JD, Hale DE, Laird A, Fox PT. Mapping structural differences of the corpus callosum in individuals with 18q deletions using targetless regional spatial normalization. Hum Brain Mapp. 2005 Apr — View Citation

Lancaster JL, Cody JD, Andrews T, Hardies LJ, Hale DE, Fox PT. Myelination in children with partial deletions of chromosome 18q. AJNR Am J Neuroradiol. 2005 Mar;26(3):447-54. — View Citation

Schaub RL, Cody JD, Hale DE. Growth disorders in the chromosome 18 syndromes. Highlights 9:3-5, 2001

Schaub RL, Hale DE, Rose SR, Leach RJ, Cody JD. The spectrum of thyroid abnormalities in individuals with 18q deletions. J Clin Endocrinol Metab. 2005 Apr;90(4):2259-63. doi: 10.1210/jc.2004-1630. Epub 2005 Jan 25. — View Citation

Schaub RL, Reveles XT, Baillargeon J, Leach RJ, Cody JD. Molecular characterization of 18p deletions: evidence for a breakpoint cluster. Genet Med. 2002 Jan-Feb;4(1):15-9. doi: 10.1097/00125817-200201000-00003. — View Citation

Sebold C, Soileau B, Heard P, Carter E, O'Donnell L, Hale DE, Cody JD. Whole arm deletions of 18p: medical and developmental effects. Am J Med Genet A. 2015 Feb;167A(2):313-23. doi: 10.1002/ajmg.a.36880. Epub 2015 Jan 14. — View Citation

Wang Z, Cody JD, Leach RJ, O'Connell P. Gene expression patterns in cell lines from patients with 18q- syndrome. Hum Genet. 1999 Jun;104(6):467-75. doi: 10.1007/s004390050989. — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary	Provide definitive medical and education resources for the families of individuals with chromosome 18 abnormalities	Ongoing

External Links

•   Click here for more information about this study: The Chromosome 18 Clinical Research Center
•   The Chromosome 18 Registry & Research Society is a lay advocacy organization composed primarily of the parents of individuals with one of the chromosome 18 abnormalities.