TSH Receptor Antibody Heterogeneity in Children and Adolescents With Graves' Disease
July 24, 2014 updated by: Rosalind Brown, Boston Children's Hospital
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medication often required for sustained immunological remission and the high risk of relapse when medication is withdrawn.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.
Study Overview
Status
Completed
Conditions
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
Enrollment (Actual)
19
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Childrens' Hospital Boston
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
2 years to 21 years (Child, Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Sampling Method
Non-Probability Sample
Study Population
Children and adolescents referred to a tertiary medical center with hyperthyroidism.
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
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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
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end of study
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
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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
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end of study
|
Other Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
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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
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end of study
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Rosalind S Brown, Children's Hosptial Boston/Harvard Medical School
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
August 1, 2005
Primary Completion (Actual)
February 1, 2010
Study Completion (Actual)
February 1, 2010
Study Registration Dates
First Submitted
June 6, 2006
First Submitted That Met QC Criteria
June 6, 2006
First Posted (Estimate)
June 8, 2006
Study Record Updates
Last Update Posted (Estimate)
July 25, 2014
Last Update Submitted That Met QC Criteria
July 24, 2014
Last Verified
July 1, 2014
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- S05-05-066
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.