Thyroid and Glucose and Energy Metabolism

NCT00106119 | Completed Phase 2 Results

• 2 other identifiers: 05011905-DK-0119
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Thyroid Diseases

Keywords

Levothyroxine; Liothyronine; Lipid Metabolism; Gluconeogensis; Thyrotropin Releasing Hormone; Deiodinase; Replacement Thyroid Hormone Therapy; Thyroidectomy; Near Total Thyroidectomy

Outcome Measures

Primary Outcomes (2)

• Insulin-mediated Glucose Disposal Rate at Levothyroxine Treatment Phase

  One month of therapy.

• Insulin-mediated Glucose Disposal Rate at Liothyronine Treatment Phase

  One month of therapy

Secondary Outcomes (12)

• Total Cholesterol at Levothyroxine Treatment Phase

  One month of therapy.

• Total Cholesterol at Liothyronine Treatment Phase

  One month of therapy.

• Triglycerides at Levothyroxine Treatment Phase

  One month of therapy.

• Triglycerides at Liothyronine Treatment Phase

  One month of therapy.

• Resting Energy Expenditure at Levothyroxine Treatment Phase

  One month of therapy.

Study Arms (1)

Liothyronine and Levothyroxine

ACTIVE COMPARATOR

Hypothyroid patients treatment with Levothyroxine and Liothyronine in 2 crossover, randomized phases

Drug: Liothyronine and Levothyroxine

Interventions

Liothyronine and Levothyroxine DRUG

Hypothyroid patients are treated with Liothyronine and Levothyroxine in 2 crossover, randomized phases

Also known as: T3 and T4

Liothyronine and Levothyroxine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (6)

• Arner P, Bolinder J, Wennlund A, Ostman J. Influence of thyroid hormone level on insulin action in human adipose tissue. Diabetes. 1984 Apr;33(4):369-75. doi: 10.2337/diab.33.4.369.

  PMID: 6423430 BACKGROUND

• Bakker SJ, ter Maaten JC, Popp-Snijders C, Slaets JP, Heine RJ, Gans RO. The relationship between thyrotropin and low density lipoprotein cholesterol is modified by insulin sensitivity in healthy euthyroid subjects. J Clin Endocrinol Metab. 2001 Mar;86(3):1206-11. doi: 10.1210/jcem.86.3.7324.

  PMID: 11238510 BACKGROUND

• Bartha T, Kim SW, Salvatore D, Gereben B, Tu HM, Harney JW, Rudas P, Larsen PR. Characterization of the 5'-flanking and 5'-untranslated regions of the cyclic adenosine 3',5'-monophosphate-responsive human type 2 iodothyronine deiodinase gene. Endocrinology. 2000 Jan;141(1):229-37. doi: 10.1210/endo.141.1.7282.

  PMID: 10614643 BACKGROUND

• Yavuz S, Linderman JD, Smith S, Zhao X, Pucino F, Celi FS. The dynamic pituitary response to escalating-dose TRH stimulation test in hypothyroid patients treated with liothyronine or levothyroxine replacement therapy. J Clin Endocrinol Metab. 2013 May;98(5):E862-6. doi: 10.1210/jc.2012-4196. Epub 2013 Apr 12.

  PMID: 23585666 DERIVED

• Celi FS, Zemskova M, Linderman JD, Smith S, Drinkard B, Sachdev V, Skarulis MC, Kozlosky M, Csako G, Costello R, Pucino F. Metabolic effects of liothyronine therapy in hypothyroidism: a randomized, double-blind, crossover trial of liothyronine versus levothyroxine. J Clin Endocrinol Metab. 2011 Nov;96(11):3466-74. doi: 10.1210/jc.2011-1329. Epub 2011 Aug 24.

  PMID: 21865366 DERIVED

• Celi FS, Zemskova M, Linderman JD, Babar NI, Skarulis MC, Csako G, Wesley R, Costello R, Penzak SR, Pucino F. The pharmacodynamic equivalence of levothyroxine and liothyronine: a randomized, double blind, cross-over study in thyroidectomized patients. Clin Endocrinol (Oxf). 2010 May;72(5):709-15. doi: 10.1111/j.1365-2265.2009.03700.x.

  PMID: 20447070 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Thyroid Diseases

Interventions

Triiodothyronine; Thyroxine

Condition Hierarchy (Ancestors)

Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thyronines; Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr. Kong Chen
• Organization: National Institute of Diabetes and Digestive and Kidney Diseases

chenkong@niddk.nih.gov

3014511636

Study Officials

• Kong Y Chen, Ph.D.

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Investigator

Study Record Dates

• First Submitted: March 19, 2005
• First Posted: March 21, 2005
• Study Start: March 1, 2005
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: February 23, 2015
• Results First Posted: February 23, 2015

Record last verified: 2015-02

Locations

US (1)