Pharmacogenomic Response to Thyrotropin-Releasing Hormone Stimulation in Healthy Volunteers: The Influence of a Common Type 2 Deiodinase Genetic Polymorphism on Serum T3

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00812149
First received: December 19, 2008
Last updated: May 20, 2014
Last verified: May 2014
  Purpose

This study intends to examine how a common genetic pattern affects thyroid function. Recent studies have demonstrated that a substance (enzyme) produced by a gene has an important role in controlling circulating thyroid hormone levels. A commonly found pattern in this gene exists in many individuals and might affect the function of the enzyme. These individuals need higher doses of thyroid hormone medication in certain situations (e.g. in the treatment of thyroid cancer after the thyroid gland has been removed) than those individuals without the variation.

We intend to study this by looking at the response to a hormone-test in healthy volunteers with different genetic patterns.

We plan to screen healthy volunteers using a blood test to identify their genetic pattern relating to the enzyme we are interested in. From this group, forty-five healthy volunteers will be recruited for the hormone-test. This test (called the TRH test) uses a hormone produced by the brain and stimulates the pituitary and thyroid gland. The response to this test will allow us to compare the function of the thyroid system in relation to the genetic pattern of the volunteer.

We hypothesize that the stimulation of the thyroid hormone system will be decreased in volunteers with a specific genetic pattern and that these individuals will release less active thyroid hormone from the thyroid gland in response to the TRH test.

This study will provide new information on the effect of a common genetic pattern on thyroid hormone function and will help us to better understand the way in which the thyroid hormone system operates. Ultimately, the results of this study might help to provide a more individualized therapy for patients in need of thyroid hormone replacement.


Condition
Thyroid Disease
Healthy

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Pharmacogenomic Response to Thyrotropin-Releasing Hormone Stimulation in Healthy Volunteers:The Influence of a Common Type 2 Deiodinase Genetic Polymorphism on Serum T3

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Enrollment: 86
Study Start Date: December 2008
Estimated Study Completion Date: May 2014
Detailed Description:

This study intends to examine how a common genetic pattern affects thyroid function. Recent studies have demonstrated that a substance (enzyme) produced by a gene has an important role in controlling circulating thyroid hormone levels. A commonly found pattern in this gene exists in many individuals and might affect the function of the enzyme. These individuals need higher doses of thyroid hormone medication in certain situations (e.g. in the treatment of thyroid cancer after the thyroid gland has been removed) than those individuals without the variation.

We intend to study this by looking at the response to a hormone-test in healthy volunteers with different genetic patterns.

We plan to screen healthy volunteers using a blood test to identify their genetic pattern relating to the enzyme we are interested in. From this group, forty-five healthy volunteers will be recruited for the hormone-test. This test (called the TRH test) uses a hormone produced by the brain and stimulates the pituitary and thyroid gland. The response to this test will allow us to compare the function of the thyroid system in relation to the genetic pattern of the volunteer.

We hypothesize that the stimulation of the thyroid hormone system will be decreased in volunteers with a specific genetic pattern and that these individuals will release less active thyroid hormone from the thyroid gland in response to the TRH test.

This study will provide new information on the effect of a common genetic pattern on thyroid hormone function and will help us to better understand the way in which the thyroid hormone system operates. Ultimately, the results of this study might help to provide a more individualized therapy for patients in need of thyroid hormone replacement.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. Subjects will be healthy male and female adult volunteers, between the ages of 18 and 65, able to provide informed consent. Patients younger than 18 are excluded as this is a purely physiologic study and we are unable to justify any potential risk. However, should our preliminary findings show potential clinically relevant benefits for children, the protocol could be modified to include them. Patients older than 65 are excluded due to intrinsic differences in thyroid hormone dynamics, compared with younger subjects, which could confound study interpretation.

EXCLUSION CRITERIA:

  1. BMI less than or equal to 19 or greater than or equal to 35 Kg/m(2)
  2. Hypothyroidism, or TSH levels above the normal limits (current replacement therapy or TSH greater than 4.0 mcIU/mL)
  3. Hyperthyroidism, or TSH levels below the normal limits (current or previous therapy or TSH less than 0.4 mcIU/mL)
  4. Autoimmune thyroid disease (as defined by a positive anti-TPO, or anti-TSH receptor antibody titer)
  5. Hypertension (Blood pressure greater than 140/90 or use of antihypertensive medication)
  6. Liver disease or ALT serum concentrations greater than 1.5 times the upper laboratory reference limit.
  7. Renal insufficiency or estimated creatinine clearance less than or equal to 50 mL/min (MDRD equation).
  8. History of, and/or current Diabetes Mellitus (fasting glucose greater than 126 mg/dL)
  9. Iodine deficiency (spot urine iodine concentration less than 42 mcg/L)
  10. History of, and/or current coronary artery disease
  11. History of, and/or current asthma
  12. History of, and/or current seizures or chronic headache
  13. History of, and/or current depression
  14. History of pituitary tumor
  15. Pregnancy (women of child-bearing potential must have a negative pregnancy test prior to inclusion and at the time of TRH testing)
  16. Known allergy to TRH
  17. Current use of prescription medication or certain non-prescription medications and dietary supplements which could affect thyroid function and/or metabolism.
  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: NCT00812149

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Francesco S Celi, M.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00812149     History of Changes
Other Study ID Numbers: 090058, 09-DK-0058
Study First Received: December 19, 2008
Last Updated: May 20, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Type-2 Deiodinase
Genetic Polymorphism
Triiodothyronine (T3)
Thyrotropin Releasing Hormone (TRH) Test

Additional relevant MeSH terms:
Thyroid Diseases
Endocrine System Diseases
Hormones
Thyrotropin-Releasing Hormone
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 01, 2014