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

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

Tracking Information
First Submitted Date June 6, 2006
First Posted Date June 8, 2006
Last Update Posted Date July 25, 2014
Study Start Date August 2005
Actual Primary Completion Date February 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 24, 2014)
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 ]
Original Primary Outcome Measures Not Provided
Change History Complete list of historical versions of study NCT00335062 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: July 24, 2014)
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 ]
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: July 24, 2014)
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 ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title TSH Receptor Antibody Heterogeneity in Children and Adolescents With Graves' Disease
Official Title TSH Receptor Antibody Heterogeneity in Children and Adolescents With Graves' Disease
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medication often required for sustained immunological remission and the high risk of relapse when medication is withdrawn.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.
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.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
whole blood, serum, white cells.
Sampling Method Non-Probability Sample
Study Population Children and adolescents referred to a tertiary medical center with hyperthyroidism.
Condition Graves' Disease
Intervention Not Provided
Study Groups/Cohorts Not Provided
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 24, 2014)
19
Original Enrollment
 (submitted: June 6, 2006)
50
Actual Study Completion Date February 2010
Actual Primary Completion Date February 2010   (Final data collection date for primary outcome measure)
Eligibility 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
Sex/Gender
Sexes Eligible for Study: All
Ages 2 Years to 21 Years   (Child, Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT00335062
Other Study ID Numbers S05-05-066
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Rosalind Brown, Boston Children’s Hospital
Study Sponsor Boston Children’s Hospital
Collaborators Not Provided
Investigators
Principal Investigator: Rosalind S Brown Children's Hosptial Boston/Harvard Medical School
PRS Account Boston Children’s Hospital
Verification Date July 2014