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Thyroid and Glucose and Energy Metabolism

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ClinicalTrials.gov Identifier: NCT00106119
Recruitment Status : Completed
First Posted : March 21, 2005
Results First Posted : February 23, 2015
Last Update Posted : February 23, 2015
Sponsor:
Information provided by (Responsible Party):
Kong Chen, Ph.D., National Institutes of Health Clinical Center (CC)

March 19, 2005
March 21, 2005
November 12, 2014
February 23, 2015
February 23, 2015
March 2005
November 2013   (Final data collection date for primary outcome measure)
  • Insulin-mediated Glucose Disposal Rate at Levothyroxine Treatment Phase [ Time Frame: One month of therapy. ]
  • Insulin-mediated Glucose Disposal Rate at Liothyronine Treatment Phase [ Time Frame: One month of therapy ]
Not Provided
Complete list of historical versions of study NCT00106119 on ClinicalTrials.gov Archive Site
  • Total Cholesterol at Levothyroxine Treatment Phase [ Time Frame: One month of therapy. ]
  • Total Cholesterol at Liothyronine Treatment Phase [ Time Frame: One month of therapy. ]
  • Triglycerides at Levothyroxine Treatment Phase [ Time Frame: One month of therapy. ]
  • Triglycerides at Liothyronine Treatment Phase [ Time Frame: One month of therapy. ]
  • Resting Energy Expenditure at Levothyroxine Treatment Phase [ Time Frame: One month of therapy. ]
  • Resting Energy Expenditure at Liothyronine Treatment Phase [ Time Frame: One month of therapy. ]
  • Left Ventricle Mass Index at Levothyroxine Treatment Phase [ Time Frame: One month of therapy. ]
  • Left Ventricle Mass Index at Liothyronine Treatment Phase [ Time Frame: One month of therapy. ]
  • Apolipoprotein A-I at Levothyroxine Treatment Phase [ Time Frame: One month of therapy. ]
  • Apolipoprotein A-I at Liothyronine Treatment Phase [ Time Frame: One month of therapy. ]
  • Apolipoprotein B at Levothyroxine Treatment Phase [ Time Frame: One month of therapy. ]
  • Apolipoprotein B at Liothyronine Treatment Phase [ Time Frame: One month of therapy. ]
Not Provided
Not Provided
Not Provided
 
Thyroid and Glucose and Energy Metabolism
Peripheral Thyroid Hormone Conversion and Glucose and Energy Metabolism

This study will examine how two thyroid preparations-levothyroxine (T4) and liothyronine (T3)-affect fat and cholesterol metabolism, blood sugar regulation, and thyrotropin secretion in patients who have had their thyroid gland removed. Results of the study may help in the development of better therapies to optimize blood sugar and cholesterol levels in some patients.

Patients 18 years of age or older who have had most or all of their thyroid gland removed and are taking long-term thyroid hormone medication may be eligible for this study after screening.

Thyroid hormone action plays an important role in the regulation of many physiologic processes, among them glucose and lipid metabolism. Interestingly, the clinical presentation of thyroid dysfunction is extremely variable, with relatively poor correlation between circulating hormone levels and clinical features. This finding suggests that the local, intracellular concentration of the active hormone liothyronine (T3), regulated by peripheral conversion of the pro-hormone levothyroxine (T4), is an important determinant in the maintenance of the thyroidal homeostasis.

The aim of the present study is the evaluation of the role of peripheral thyroid hormone conversion in the regulation of glucose and lipid metabolism by assessing the differential response to T4 or T3 treatment in subjects devoid of endogenous thyroid hormone production. T3 administration bypasses peripheral metabolism and therefore will allow us to assess the role of the peripheral thyroid hormone conversion in the regulation of the hormone action at the end-organ level.

Fifty hypothyroid subjects will be initially randomized to either of the thyroid hormone replacements liothyronine (T3) or levothyroxine (T4) treatment period (one arm cross-over design, with treatment sequence randomized), aimed to maintain serum TSH levels greater than or equal to 0.5 less than or equal to 1.5 mU/L, indicating full replacement. After a 30-day period of steady-state replacement the study subjects will be admitted to the Clinical Center and, after a three-day period of stabilization and an overnight fast, will undergo the following tests: escalating dose TRH stimulation test, indirect calorimetry, graded exercise tolerance test, DEXA scan, and echocardiogram.

Patients will also undergo skeletal muscle biopsy and subcutaneous adipose tissue biopsy and microdialysis, as well as a two-step euglycemic hyperinsulinemic clamp with measurement of splanchnic gluconeogenesis. Fasting venous blood samples will be collected for the determination of the parameters of lipid, glucose and energy metabolism.

After discharge, the patients will switch to the other form of thyroid hormone replacement therapy (second period) . The therapy will be adjusted in order to achieve the same therapeutic goal for TSH concentrations (greater than or equal to 0.5 less than or equal to 1.5 mU/L), analogous to that achieved during the first phase of the study (TSH less than or equal to 0.5 mU/L difference between T3 and T4 phases). After reaching a 30-day period of steady-state replacement, study subjects will be re-admitted to the Clinical Center and the previously described evaluation procedures will be repeated.

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Thyroid Diseases
Drug: Liothyronine and Levothyroxine
Hypothyroid patients are treated with Liothyronine and Levothyroxine in 2 crossover, randomized phases
Other Name: T3 and T4
Active Comparator: Liothyronine and Levothyroxine
Hypothyroid patients treatment with Levothyroxine and Liothyronine in 2 crossover, randomized phases
Intervention: Drug: Liothyronine and Levothyroxine

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
18
50
November 2013
November 2013   (Final data collection date for primary outcome measure)
  • INCLUSION CRITERIA:

Age greater than or equal to 18 years, male or female.

History of total or near total thyroidectomy or hypothyroidism on replacement therapy.

For non-thyroidectomized patients, at least three-year history of replacement therapy (at least 1.2 mcg/Kg LT4/body weight), and less than 5% uptake at 24H on (123)I thyroid scan while on replacement therapy.

Written informed consent.

EXCLUSION CRITERIA:

BMI less than or equal to 20 or greater than or equal to 30 kg/m(2).

Metastatic thyroid cancer or history of thyroid cancer with high risk of recurrence requiring suppressive thyroid hormone therapy (Singer 1996).

Significant thyroid residual greater than 1 mL as measured by ultrasound (limited to thyroidectomized patients) or greater than 5 percent uptake at 24H on (123)I thyroid scan while on replacement therapy (limited to hypothyroid patients not undergone total thyroidectomy).

History or symptoms compatible with cardiovascular disease, including paroxysmal supraventricular tachycardia, atrial fibrillation, syncopal episodes or use of prescription medications for heart conditions, including antihypertensives.

Allergy to lidocaine, isoproterenol, TRH, levothyroxine, liothyronine, Tylenol #3, oxycodone, nitroglycerin.

Pregnancy or unwillingness to use non-hormonal contraception during the study.

Breastfeeding

Use of hormonal contraceptives or estrogen replacement therapy.

Use of tobacco (smoking, chewing) for the two weeks preceding the hospital admissions (metabolic testing)

Diabetes mellitus, either type I or II.

Hypercholesterolemia (serum levels greater than or equal to 240 mg/dL), hypertriglyceridemia (plasma levels greater than or equal to 220 mg/dL) and/or use of antilipemic therapy.

Liver disease or ALT serum level greater than two fold the upper laboratory reference limit.

Renal insufficiency or estimated creatinine clearance less than or equal to 50 mL/min.

Use of medications/supplements/alternative therapies known to alter thyroid function.

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

Use of antipsychotic medications

History of drug or alcohol abuse within the last 5 years; current use of drugs or alcohol (CAGE greater than 3).

Keloid formation (relative to skeletal muscle and subcutaneous adipose tissue biopsies).

Current or previous clinically significant (requiring medical/surgical intervention) extrathyroidal manifestations of autoimmune thyroid disease (dermopathy, ophthalmopathy, arthropathy).

Sexes Eligible for Study: All
18 Years to 65 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00106119
050119
05-DK-0119 ( Other Identifier: NIH )
No
Not Provided
Not Provided
Kong Chen, Ph.D., National Institutes of Health Clinical Center (CC)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Not Provided
Principal Investigator: Kong Y Chen, Ph.D. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institutes of Health Clinical Center (CC)
February 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP