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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Rosalind Brown, Children's Hospital Boston
ClinicalTrials.gov Identifier:
NCT00335062
First received: June 6, 2006
Last updated: July 24, 2014
Last verified: July 2014

June 6, 2006
July 24, 2014
August 2005
February 2010   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00335062 on ClinicalTrials.gov Archive Site
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 ] [ Designated as safety issue: No ]
Not Provided
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 ] [ Designated as safety issue: No ]
Not Provided
 
TSH Receptor Antibody Heterogeneity in Children and Adolescents With Graves' Disease
TSH Receptor Antibody Heterogeneity in Children and Adolescents With Graves' Disease

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medication often required for sustained immunological remission and the high risk of relapse when medication is withdrawn.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.

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.

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

whole blood, serum, white cells.

Non-Probability Sample

Children and adolescents referred to a tertiary medical center with hyperthyroidism.

Graves' Disease
Not Provided
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
19
February 2010
February 2010   (final data collection date for primary outcome measure)

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
Both
2 Years to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00335062
S05-05-066
Yes
Rosalind Brown, Children's Hospital Boston
Children's Hospital Boston
Not Provided
Principal Investigator: Rosalind S Brown Children's Hosptial Boston/Harvard Medical School
Children's Hospital Boston
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP