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
  Purpose

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medication often required for sustained immunological remission and the high risk of relapse when medication is withdrawn.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 Phase
Graves' Disease
Phase 1

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: TSH Receptor Antibody Heterogeneity in Children and Adolescents With Graves' Disease

Resource links provided by NLM:


Further study details as provided by Children's Hospital Boston:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Other Outcome Measures:
  • 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 ]

Biospecimen Retention:   Samples With DNA

whole blood, serum, white cells.


Enrollment: 19
Study Start Date: August 2005
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   2 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

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

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00335062

Locations
United States, Massachusetts
Childrens' Hospital Boston
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Children's Hospital Boston
Investigators
Principal Investigator: Rosalind S Brown Children's Hosptial Boston/Harvard Medical School
  More Information

Additional Information:
No publications provided

Responsible Party: Rosalind Brown, Director of Clinical Trials, Children's Hospital Boston
ClinicalTrials.gov Identifier: NCT00335062     History of Changes
Other Study ID Numbers: S05-05-066
Study First Received: June 6, 2006
Last Updated: July 24, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Children's Hospital Boston:
Autoimmune thyroid disease
Children and Adolescents
TSH Receptor Antibodies

Additional relevant MeSH terms:
Graves Disease
Exophthalmos
Orbital Diseases
Eye Diseases
Goiter
Thyroid Diseases
Endocrine System Diseases
Hyperthyroidism
Autoimmune Diseases
Immune System Diseases
Antibodies
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 26, 2014