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Pharmacokinetic and Pharmacodynamic Studies of Liothyronine. A Study on the Metabolic Effects of Thyroid Hormone


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Malignant Struma Ovarii, Papillary Thyroid Cancer, Hurthle Cell Thyroid Cancer, Follicular Thyroid Cancer, Tall Cell Variant Thyroid Cancer

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Trial Information

Pharmacokinetic and Pharmacodynamic Studies of Liothyronine. A Study on the Metabolic Effects of Thyroid Hormone


In human adults thyroid hormone action plays a critical role in the modulation of metabolism
and the function of virtually all organ/systems. The specificity of the hormonal action is
ultimately the result of the interaction of the active hormone, triiodothyronine (T3), with
the receptors' isoforms and the co-activators and co-repressors specific for the various
cells target of the hormonal action. Circulating and tissue levels of T3 are the result of
the secretion of T3 and its precursor, thyroxine (T4), from the thyroid gland, the
peripheral conversion of T4 into T3, and the degradation of these hormones. This complex
system has only been partially studied in humans and very little is known regarding the
kinetics of T3, and in particular on the correlation between circulating levels of T3 and
end-organ target tissue thyroid hormone action. The aim of this protocol is to characterize
the pharmacokinetics of T3 and its biological effects at various concentrations in a cohort
of thyroidectomized patients undergoing thyroid hormone replacement therapy withdrawal for
the management of thyroid cancer.

Fifteen patients with a clinical indication for thyroid hormone withdrawal in preparation
for 131I therapy or 123I diagnostic scan for follow-up and management of differentiated
thyroid cancer will be recruited for this study. After enrollment in the study, the
patients' baseline characteristics will be determined during an outpatient visit while
receiving levothyroxine (L-T4) therapy. The L-T4 therapy then will be suspended and
substituted with an equivalent thrice daily liothyronine (L-T3) therapy for one month.
Patients will be admitted to the NIH Clinical Center on the day prior to withdrawal of the
T3 therapy until the diagnostic scan or the administration of radioactive iodine. During the
hospitalization for this research protocol, which is expected to last eleven days, the
following studies will be performed: serial blood sampling for circulating thyroid hormones
to obtain pharmacokinetic parameters of L-T3, lipids, glucose and insulin, resting energy
expenditure, echocardiogram, skeletal muscle strength measurement, cardiac, hepatic and
skeletal muscles MRI, and quality of life and well-being questionnaires. The pharmacokinetic
parameters of L-T3 will also be assessed with the first dose after the diagnostic scan or
the administration of radioactive iodine. The results obtained from this study will help in
understanding the effects of thyroid hormone on metabolism, and may lead to important
information on how to optimize the duration of the thyroid hormone therapy withdrawal for
the treatment of thyroid cancer.

Inclusion Criteria


- INCLUSION CRITERIA:

Subjects will be adult volunteers older than age 18 who underwent total thyroidectomy for
the treatment of differentiated thyroid cancer, previously undergone radioactive iodine
ablation of the thyroid gland remnant, with clinical indication for withdrawal from
thyroid hormone replacement therapy in preparation for nuclear medicine imaging or
therapeutic procedures with radioactive iodine. The patient population will be recruited
from the participants in the 77-DK-0096 natural history protocol: Studies on Thyroid
Nodules and Thyroid Cancer , PI Monica C. Skarulis and from the 10-C-0102 natural history
protocol: Clinical and Genetic Studies in Familial Non-Medullary Thyroid Cancer , PI
Electron Kebebew.

EXCLUSION CRITERIA:

1. Significant thyroid residual greater than 5 gm as measure by ultrasound or greater
than 5 percent uptake at 24 H on (123) I pre-treatment thyroid scan.

2. Renal insufficiency or estimated creatinine clearance less than or equal to 60
mL/min/1.73M(2) BSA by MDRD equation before thyroid hormone withdrawal.

3. Liver disease or ALT > 2.5 times the upper laboratory reference limit.

4. Pharmacologic therapy for the treatment of psychiatric conditions.

5. History of, and/or current coronary artery disease.

6. Current history or symptoms compatible with psychosis or major depression (including
history of hospitalization for depression, history of attempted suicide, history of
suicidal ideation). Use of antipsychotic medications.

7. History of drug or alcohol abuse within the last year; current use of illicit drugs
or alcohol abuse (CAGE> 3).

8. Pregnancy (women of child-bearing potential must have a negative pregnancy test prior
to inclusion) or use of hormonal contraceptives.

9. Known allergy to L-T3.

10. Current use of prescription medication or certain non-prescription medications and
dietary supplements known to affect thyroid function and/or metabolism, or alter the
pharmacokinetics of L-T3.

11. Inability or unwillingness to follow the low-iodine, metabolic diet or non-compliance
to the L-T3 administration regimen.

12. The presence of persistent diarrhea or malabsorption syndromes that would interfere
with the patient's ability to adequately absorb drugs.

13. Inability to obtain venous access for sample collection, or basal hemoglobin of less
than or equal to 10 g/dL.

14. Low functional status (ECOG Performance Status > 2)

Type of Study:

Observational

Study Design:

Time Perspective: Prospective

Principal Investigator

Francesco S Celi, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Authority:

United States: Federal Government

Study ID:

110256

NCT ID:

NCT01441154

Start Date:

September 2011

Completion Date:

Related Keywords:

  • Malignant Struma Ovarii
  • Papillary Thyroid Cancer
  • Hurthle Cell Thyroid Cancer
  • Follicular Thyroid Cancer
  • Tall Cell Variant Thyroid Cancer
  • Hypothyroidism
  • Thyroid Cancer
  • Triiodothyronine (T3)
  • Energy Expenditure
  • Thyroid Hormone
  • Thyroid Neoplasms
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
  • Struma Ovarii
  • Thyroid Diseases
  • Adenocarcinoma, Follicular

Name

Location
National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892