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TSH Receptor Antibody Heterogeneity in Children and Adolescents With Graves' Disease

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. Identifier: NCT00335062
Recruitment Status : Completed
First Posted : June 8, 2006
Last Update Posted : July 25, 2014
Information provided by (Responsible Party):
Rosalind Brown, Boston Children's Hospital

Brief Summary:
Graves' disease, the most common form of hyperthyroidism in children, is caused by Thyrotropin (TSH) Receptor Antibodies (TRAbs) that mimic the action of TSH. The disease leads to significant morbidity in children both due to the prolonged course of antithyroid medication often required for sustained immunological remission and the high risk of relapse when medication is withdrawn. The ability to predict which patients are most likely to fail medical management would greatly improve the choice of therapy. In the past, large goiter size, age at diagnosis, increased biochemical severity, and decreased body mass index have all been associated with a poorer prognosis, but these clinical indicators lack sensitivity and specificity. Preliminary data suggest that the new TRAb assays are both sensitive and specific for the measurement of TRAbs in children with Graves' disease. In addition, variation in these antibodies over time is not the same in all patients. The goal of this proposal will be to prospectively follow children with newly diagnosed Graves' disease and use microarray technology to determine if there are genes whose expression differ in patients who respond to medical therapy versus those who will need more definitive therapy earlier in their disease.

Condition or disease
Graves' Disease

Detailed Description:
In the present grant proposal, we plan to utilize two new assays (binding and bioassay) in order to identify additional predictors of Graves' disease and apply them to a well characterized group of patients with Graves' disease followed prospectively. More specifically, we plan to further investigate the antibodies by measuring lambda: kappa light chain antibody ratios in pediatric patients. We will assess epitope heterogeneity by using novel chimeric proteins in which specific portions of the TSH receptor have been replaced with the closely related LH receptor. We will utilize microarray technology to determine if there are differences in gene expression profiles in responders versus non responders. It is hoped that these methods will lead to an improved ability to follow disease progression and to monitor efficacy of therapy.

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Study Type : Observational
Actual Enrollment : 19 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: TSH Receptor Antibody Heterogeneity in Children and Adolescents With Graves' Disease
Study Start Date : August 2005
Actual Primary Completion Date : February 2010
Actual Study Completion Date : February 2010

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. The primary outcome will be the disappearance of TSH receptor Abs (as assessed by both ELISA and bioassay) from the circulation. [ Time Frame: end of study ]

Secondary Outcome Measures :
  1. 2) The secondary outcome will be normalization of thyroid function tests (T4, free T4, Total T3, and TSH) on a low dose of Tapazole 2.5-5.0 mg per day. [ Time Frame: end of study ]

Other Outcome Measures:
  1. 3) In the neonatal Graves' disease patient, the primary outcome will be the clearance of both TBII and TSI from the infant's sera (as assessed by both ELISA and bioassay). [ Time Frame: end of study ]

Biospecimen Retention:   Samples With DNA
whole blood, serum, white cells.

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Children and adolescents referred to a tertiary medical center with hyperthyroidism.

Inclusion Criteria:

  • Age 2-21 years
  • Suppressed Thyroid Stimulating Hormone (TSH)
  • Elevated Triiodothyronine (T3), Thyroxine (T4)

Exclusion Criteria:

  • Pregnancy
  • Toxic Nodule
  • Currently receiving steroids or thyroid hormone replacement
  • Bacterial, Viral, Radiation, or Autoimmune thyroiditis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00335062

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United States, Massachusetts
Childrens' Hospital Boston
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Boston Children's Hospital
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Principal Investigator: Rosalind S Brown Children's Hosptial Boston/Harvard Medical School
Additional Information:
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Responsible Party: Rosalind Brown, Director of Clinical Trials, Boston Children's Hospital Identifier: NCT00335062    
Other Study ID Numbers: S05-05-066
First Posted: June 8, 2006    Key Record Dates
Last Update Posted: July 25, 2014
Last Verified: July 2014
Keywords provided by Rosalind Brown, Boston Children's Hospital:
Autoimmune thyroid disease
Children and Adolescents
TSH Receptor Antibodies
Additional relevant MeSH terms:
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Graves Disease
Orbital Diseases
Eye Diseases
Thyroid Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases